Mercury bioaccumulation and trophic transfer in Pacific Saury from the North Pacific Ocean.

This study investigates mercury (Hg) dynamics in Pacific Saury (Cololabis saira) across the North Pacific Ocean, specifically off East Japan in 2018. Saury traits vary with total mercury (THg) concentrations in muscle tissues ranging from 0.017 to 0.082 µg g-1 w. w., averaging of 0.042 (n = 46). A positive correlation between THg and saury length (Knob length, 270-319 mm) indicates increased Hg concentration with size. Stable isotopic tracers suggest Pacific Euphausiids (Krill) are significant contributors to the saury diet (>70% of total). Significant correlations between logarithm THg concentration (Log THg) and δ15N (‰) (R2 = 0.70) demonstrate Hg trophic biomagnification, with regional variations. Comparative analysis between the eastern (ENPO) and western North Pacific Ocean (WNPO) indicates differences, with WNPO saury exhibiting lower δ15N values and higher THg levels than ENPO saury. This suggests that the WNPO, located near East Asia, the world's largest Hg emitter, experiences elevated Hg levels in seawater due to anthropogenic release. Overall, this study advances understanding of Pacific Saury's ecological interactions and Hg bioaccumulations, emphasizing the importance of species-specific behaviors and regional influences in ecological studies.

Increasing structure diversity of farnesylated chalcones by a fungal aromatic prenyltransferase.

Farnesylated chalcones were favored by researchers due to their different biological activities. However, only five naturally occurring farnesylated chalcones were described in the literature until now. Here, the farnesylation of six chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT was reported. Fourteen monofarnesylated chalcones (1F1-1F5, 2F1-2F3, 3F1, 3F2, 4F1, 4F2, 5F1, 6F1, and 6F2) and a difarnesylated product (2F3) were obtained, enriching the diversity of natural farnesylated chalcones significantly. Ten of them are C-farnesylated products, which complement O-farnesylated chalcones by chemical synthesis. Fourteen products have not been reported prior to this study. Nine of the produced compounds (1F2-1F5, 2F1-2F3, 5F1, and 6F1) exhibited inhibitory effect on α-glucosidase with IC50 values ranging from 24.08 ± 1.44 to 190.0 ± 0.28 µM. Among them, compounds 2F3 with IC50 value at 24.08 ± 1.44 µM and 1F4 with IC50 value at 30.09 ± 0.59 µM showed about 20 times stronger than the positive control acarbose with an IC50 at 536.87 ± 24.25 µM in α-glucosidase inhibitory assays.

Fungal Prenyltransferase AnaPT and Its F265 Mutants Catalyze the Dimethylallylation at the Nonaromatic Carbon of Phloretin.

Phloretin is widely found in fruit and shows various biological activities. Here, we demonstrate the dimethylallylation, geranylation, and farnesylation, particularly the first dimethylallylation at the nonaromatic carbon of phloretin (1) by the fungal prenyltransferase AnaPT and its mutants. F265 was identified as a key amino acid residue related to dimethylallylation at the nonaromatic carbon of phloretin. Mutants AnaPT_F265D, AnaPT_F265G, AnaPT_F265P, AnaPT_F265C, and AnaPT_F265Y were discovered to generally increase prenylation activity toward 1. AnaPT_F265G catalyzes the O-geranylation selectively at the C-2' hydroxyl group, which involves an intramolecular hydrogen bond with the carbonyl group of 1. Seven products, 1D5, 1D7-1D9, 1G2, 1G4, and 1F2, have not been reported prior to this study. Twelve compounds, 1D3-1D9, 1G1-1G3, and 1F1-1F2, exhibited potential inhibitory effects on α-glucosidase with IC50 values ranging from 11.45 ± 0.87 to 193.80 ± 6.52 µg/mL. Among them, 1G1 with an IC50 value of 11.45 ± 0.87 µg/mL was the most potential α-glucosidase inhibitor, which is about 30 times stronger than the positive control acarbose with an IC50 value of 346.63 ± 15.65 µg/mL.

Aloperine-Type Alkaloids with Antiviral and Antifungal Activities from the Seeds of Sophora alopecuroides L.

As a continuous flow investigation of novel pesticides from natural quinolizidine alkaloids, the chemical compositions of the seeds of Sophora alopecuroides were thoroughly researched. Fifteen new aloperine-type alkaloids (1-15) as well as six known aloperine-type alkaloids (16-21) were obtained from the extract of S. alopecuroides. The structures of 1-21 were confirmed via HRESIMS, NMR, UV, IR, ECD calculations, and X-ray diffraction. The antiviral activities of 1-21 against tobacco mosaic virus (TMV) were detected following the improved method of half-leaf. Compared with ningnanmycin (protective: 69.7% and curative: 64.3%), 15 exhibited excellent protective (71.7%) and curative (64.6%) activities against TMV. Further biological studies illustrated that 15 significantly inhibited the transcription of the TMV-CP gene and increased the activities of polyphenol oxidase (PPO), peroxidase (POD), superoxide dismutase (SOD), and phenylalanine ammonia-lyase (PAL). The antifungal activities of 1-21 against Phytophythora capsica, Botrytis cinerea, Alternaria alternata, and Gibberella zeae were screened according to a mycelial inhibition test. Compound 13 displayed excellent antifungal activity against B. cinerea (EC50: 7.38 µg/mL). Moreover, in vitro antifungal mechanism studies displayed that 13 causes accumulation of reactive oxygen species and finally leads to mycelia cell membrane damage and cell death in vitro.

Isolating Antipathogenic Fungal Coumarins from Coriaria nepalensis and Determining Their Primary Mechanism In Vitro.

Through bioassay-guided isolation, eight undescribed coumarins (1-8), along with six reported coumarins (9-14), were obtained from Coriaria nepalensis. The new structures were determined by using IR, UV, NMR, HRESIMS, and ECD calculations. The results of the biological activity assays showed that compound 9 exhibited broad spectrum antifungal activities against all tested fungi in vitro and a significant inhibitory effect on Phytophthora nicotianae with an EC50 value of 3.00 µg/mL. Notably, compound 9 demonstrated greater curative and protective effects against tobacco balack shank than those of osthol in vivo. Thus, 9 was structurally modified to obtain new promising antifungal agents, and the novel derivatives (17b, 17j, and 17k) exhibited better effects on Sclerotinia sclerotiorum than did lead compound 9. Preliminary mechanistic exploration illustrated that 9 could enhance cell membrane permeability, destroy the morphology and ultrastructure of cells, and reduce the exopolysaccharide content of P. nicotianae mycelia. Furthermore, the cytotoxicity results revealed that compound 9 exhibited relatively low cytotoxicity against HEK293 cell lines with an inhibition rate of 33.54% at 30 µg/mL. This research is promising for the discovery of new fungicides from natural coumarins with satisfactory ecological compatibility.

Quinolizidine Alkaloids and Isoflavones from the Herb of Thermopsis lupinoides and Their Antiviral, Antifungal, and Insecticidal Activities.

As part of our ongoing investigation of natural bioactive substances from the genus Thermopsis of the tribe Fabaceae for agricultural protection, the chemical constituents of the herb Thermopsis lupinoides were systematically investigated, which led to the isolation of 39 quinolizidine alkaloids (QAs) (1-39), including 14 new QAs (1-14) and 14 isoflavones (40-53). Their structures were elucidated through comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS), ECD calculations, and X-ray crystallography. The antitomato spotted wilt virus (TSWV) and antifungal (against Botrytis cinerea, Gibberella zeae, Phytophythora capsica, and Alternaria alternata) and insecticidal (against Aphis fabae and Tetranychus urticae) activities of the isolated compounds were screened using the lesion counting method, mycelial inhibition assay, and spray method, respectively. The bioassay results showed that 34 exhibited excellent protective activity against TSWV, with an EC50 value of 36.04 µg/mL, which was better than that of the positive control, ningnanmycin (86.03 µg/mL). The preliminary mechanistic exploration illustrated that 34 induced systemic acquired resistance in the host plant by acting on the salicylic acid signaling pathway. Moreover, 1 showed significant antifungal activity against B. cinerea (EC50 value of 20.83 µg/mL), while 2 exhibited good insecticidal activity against A. fabae (LC50 value of 24.97 µg/mL). This research is promising for the invention of novel pesticides from QAs with high efficiency and satisfactory ecological compatibility.

Three new quinolizidine alkaloids from the roots of Sophora tonkinensis.

Three new quinolizidine alkaloids (1 - 3), including one new naturally isoflavone and cytisine polymer (3), along with 6 known ones were isolated from the ethanol extract of Sophora tonkinensis Gagnep. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, HRESIMS, 1D and 2D NMR), combined with ECD calculations. The antifungal activity against Phytophythora capsica, Botrytis cinerea, Gibberella zeae, and Alternaria alternata of the compounds was evaluated in a mycelial inhibition assay. Biological tests indicated that compound 3 exhibited strong antifungal activity against P. capsica with EC50 values of 17.7 µg/ml.

Synergistic combination of isogarcinol isolated from edible fruits of Garcinia multiflora and dexamethasone to overcome leukemia glucocorticoid resistance.

Isogarcinol (ISO), a cytotoxic polycyclic polyprenylated acylphloroglucinol isolated from the edible fruits of Garcinia multiflora. However, synergistic combination of ISO and dexamethasone (DEX) to overcome leukemia glucocorticoid resistance has never been investigated. Therefore, in this study, the effects of ISO in combination with DEX was conducted on leukemia in vivo and glucocorticoid resistance in vitro. As a result, the combination of the two compounds could efficiently inhibit leukemia progression in mice and reverse DEX resistance in acute lymphoblastic leukemia (ALL) Jurkat cells. Significantly, our findings indicated that c-Myc may be a potential target of ISO, as it is involved in cell cycle arrest and apoptosis by the combination of ISO and DEX in Jurkat cells. Furthermore, western blot analysis revealed that ISO and DEX inhibits the PI3K/Akt/mTOR signaling pathway and promotes the nuclear translocation of glucocorticoid receptor (GR), which activates target genes NR3C1 and TSC22D3, leading to apoptosis in Jurkat cells. Hence, our results suggest that ISO, as a safe and effective food-derived agent, can enhance the anti-leukemia effects of DEX.

Four new pregnane C21 steroids isolated from the roots of Cynanchum auriculatum.

Four new steroids cynansteroid G-I (1-3) and cynansteroid K (4), a new natural product 5,6-deacidizingcaudatin (5), and a known compound glycocaudatin (6), were isolated from the roots of Cynanchum auriculatum. The structures of new compounds were identified by comprehensive spectroscopic analyses, including NMR, HRESI-MS, ECD, UV, and IR spectral data. The cytotoxic activities of all the isolates against two human tumour cell lines (COLO-205 and BGC-823) were screened, unfortunately, which were weaker than positive control.

UPLC-Q-Orbitrap-MS/MS-Guided Isolation of Bioactive Withanolides from the Fruits of Physalis angulata.

Physalis angulata Linn. is an exotic Amazonian fruit that is commonly recognized as wild tomato, winter cherry, and gooseberry. While its fruit is known to contain many nutrients, such as minerals, fibers, and vitamins, few papers have investigated withanolide derivatives from its fruits. UPLC-Q-Orbitrap-MS/MS, which produces fragmentation spectra, was applied for the first time to guide the isolation of bioactive withanolide derivatives from P. angulata fruits. As a result, twenty-six withanolide derivatives, including two novel 1,10-secowithanolides (1 and 2) and a new derivative (3), were obtained. Compounds 1 and 2 are rare rearranged 1,10-secowithanolides with a tetracyclic 7/6/6/5 ring system. All structures were assigned through various spectroscopic data and quantum chemical calculations. Nine withanolide derivatives exhibited significant inhibitory effects on three tumor cell lines with IC50 values of 0.51-13.79 µM. Moreover, three new compounds (1-3) exhibited potential nitric oxide inhibitory effects in lipopolysaccharide-stimulated RAW264.7 cells (IC50: 7.51-61.8 µM). This investigation indicated that fruits of P. angulata could be applied to treat and prevent cancer and inflammatory-related diseases due to their potent active withanolide derivatives.

Synthesis and Antifungal Activity of Curcumol Derivatives.

To discover novel and effective antifungal candidates, a series of new curcumol derivatives were designed, synthesized, and evaluated their antifungal activity against five phytopathogenic fungi by the mycelium growth rate method. Derivatives c4, c22 and c23 exhibited excellent antifungal activity against Phomopsis sp. with EC50 values of 3.06, 3.07, and 3.16 µM, respectively. Specifically, compound c4 exhibited the strongest antifungal activity against Phomopsis sp., which was 44 times that of pyrimethanil (EC50 =134.37 µM). The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that compound c4 could cause cell senescence and death of Phomopsis sp. by changing the normal hyphal morphology and disrupting the normal metabolism of hyphal cells. Moreover, compound c4 showed excellent curative effect against Phomopsis sp. on kiwifruit. These findings confirmed that compound c4 has great potential as a potent antifungal agent.

Principles of extramural health care for chronic wounds in China.

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.

Chemical Constituents of Primulina eburnea (Gesneriaceae) and Their Cytotoxic Activities.

Two new ursane-type triterpenes, eburnealactones A and B (1 and 2), one new flavonoid, eburneatin A (6), and one new phenylethanoid glycoside, chiritoside D (7), along with 9 known compounds (3-5, 8-13) were isolated from the whole plant of Primulina eburnea. Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HR-ESI-MS). All the compounds were evaluated for their cytotoxic activities. Compound 1 showed significant cytotoxic activities against MKN-45 cell lines and 5637 cell lines with the IC50 values of 9.57 µM and 8.30 µM, respectively. Compound 1 exhibited moderate cytotoxic activities against A549 and PATU8988T cell lines with the IC50 values of 30.70 µM and 38.22 µM, respectively. Compound 6 exhibited moderate cytotoxic activities against MKN-45, HCT116, PATU8988T, 5637 and A-673 cell lines with the IC50 values of 19.69 µM, 16.44 µM, 18.07 µM, 11.51 µM and 18.15 µM, respectively. Compound 5 showed moderate cytotoxic activities against A549 cell lines with the IC50 values of 24.06 µM.

Geranylation of Chalcones by a Fungal Aromatic Prenyltransferase.

Geranylated chalcones mainly exist in plants, and many of them have attracted attention because of their diverse pharmacological and biological activities. Herein, we report geranylation of eight chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT. Ten new mono-geranylated enzyme products (1G-5G, 6G1, 6G2, 7G, 8G1, and 8G2) were obtained. Most of the products are C-geranylated products with prenyl moieties at ring B. In comparison, plant aromatic prenyltransferases usually catalyze the geranylation at ring A. Therefore, AtaPT can be used complementarily for chalcone geranylation to increase the structural diversity of small molecules. In addition, seven compounds (1G, 3G, 4G, 6G1, 7G, 8G1, and 8G2) exhibited a potential inhibitory effect on α-glucosidase with the IC50 values ranging from 45.59 ± 3.48 to 82.85 ± 2.15 µg/mL. Among them, compound 7G (45.59 ± 3.48 µg/mL) was the most potential α-glucosidase inhibitor, which is about seven times stronger than the positive control acarbose (IC50 = 346.63 ± 15.65 µg/mL).

Matrine-Type Alkaloids with Anti-Tomato Spotted Wilt Virus Activity from the Root of Sophora tonkinensis Gagnep.

As a continuation of our research on the development of pesticide active quinolizidine alkaloids (QAs) from the family Fabaceae, the chemical constituents of the root of Sophora tonkinensis Gagnep. were systematically investigated. Seventeen new matrine-type alkaloids (1-17), including one new naturally occurring compound (17), along with 20 known ones were isolated from the EtOH extract of S. tonkinensis. Notably, compound 5 possessed an unprecedented 6/6/5/4/6/6 hexacyclic system. Their structures were confirmed via comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS), ECD calculation, and X-ray crystallography. Biological tests indicated that compounds 1, 4, 10, 12, 13, and 30 displayed significant anti-tomato spotted wilt virus (TSWV) activities compared with the positive control ningnanmycin. Moreover, compound 12 strongly inhibited the expression of the TSWV N, NSs, and NSm genes and TSWV NSs protein in plant host. Furthermore, compounds 4, 10, 12, 20, and 22 exhibited moderate insecticidal activities against TSWV thrip vector (Frankliniella occidentalis).

Five new limonoids isolated from Walsura robusta.

Five new toosendanin limonoids with highly oxidative furan ring walsurobustones A-D (1-4), and one new furan ring degraded limonoid walsurobustone E (5) together with one known compound toonapubesic acid B (6) were isolated from the leaves of Walsura robusta. Their structures were elucidated by NMR and MS data. Especially, the absolute configuration of toonapubesic acid B (6) was confirmed by X-ray diffraction study. Compounds 1-6 exhibited good cytotoxicity against the cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480.

Two new isoflavones from the roots of Sophora tonkinensis.

Two new isoflavones (1 and 2), as well as eight known ones were isolated from the roots of Sophora tonkinensis Gagnep. Compound 1 represents an unprecedented polymerization pattern constructed by isoflavone and cytisine. Their structures were elucidated by comprehensive spectroscopic data analysis, combined with ECD calculations. Compound 1 displayed significant anti-tobacco mosaic virus (TMV) activity compared with the positive control ningnanmycin. Moreover, compound 6 exhibited potent α-glucosidase inhibitory activity with IC50 value of 47.4 mg/L.

Rapid increase of pCO2 and seawater acidification along Kuroshio at the east edge of the East China Sea.

Rates of seawater acidification and rise of partial pressure of CO2 (pCO2) at ocean margins are highly uncertain. In this study, nine years of time-series data sampled during 2010-2018 along Kuroshio Current near the East China Sea (ECS) were investigated. We found trends of surface seawater pCO2 at 3.70 ± 0.57 µatm year-1 and pH at -0.0033 ± 0.0009 unityear-1, both of which were significantly greater than those reported from other oceanic time series. Mechanistic analysis showed that seawater warming caused rapid rates of pCO2 increase and acidification under sustained DIC increase. The faster pCO2 growth relative to the atmosphere resulted in the CO2 uptake through the air-sea exchange declining by ~50 % (~-0.8 to -0.4 mol C m-2 year-1) over the study period. Our results imply that rapidly warming boundary currents could potentially present an elevated pCO2 trend, leading to a gradual reduction and eventual loss of oceanic CO2 uptake under climate change.

Quinoline Alkaloids from the Roots of Orixa japonica with the Anti-Pathogenic Fungi Activities.

A new quinoline alkaloid, 5-hydroxy-6-methoxy-N-methyl-2-phenylquinoline-4-one (1), and seventeen known quinoline alkaloids (2-18) were isolated from the roots of Orixa japonica. The structure of 1 was determined by analysis of spectroscopic data. Among them, compounds 2, 3, and 13 were isolated from this plant for the first time. All isolates were screened for the anti-pathogenic fungi activities, including Rhizoctonia solani, Magnaporthe oryzae, and Phomopsis sp. The results showed that five compounds (4, 8, 10, 11, and 12) exhibited significant anti-pathogenic fungi effects at 50.0 µg/mL. In special, compound 10 exhibited the best antifungal activities toward R. solani and M. oryzae with the IC50 values of 37.86 and 44.72 µM, respectively, better than that of the positive control, hymexazol (IC50 121.21 and 1518.18 µM, respectively). Moreover, eleven new quinoline alkaloids derivatives (12a-12k) were designed and synthesized to investigate the structure-activity relationships (SARs). The SARs analysis indicated that the furo[2,3-b]quinoline skeleton and the methoxy at C-7 (compounds 8, 11, and 12) played a key role for improving the antifungal activities.