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Pseudallenes A and B (1 and 2), the new and rare examples of sulfur-containing ovalicin derivatives, along with three known analogues 3–5, were isolated and identified from the culture extract of Pseudallescheria boydii CS-793, a fungus obtained from the deep-sea cold seep sediments. Their structures were established by detailed interpretation of NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed and established the structures and absolute configurations of compounds 1–3, thus providing the first characterized crystal structure of an ovalicin-type sesquiterpenoid. In the antimicrobial assays, compounds 1–3 showed broad-spectrum inhibitory activities against several plant pathogens with MIC values ranging from 2 to 16 μg/mL.

Abstract Objective This study aimed to develop a preoperative nomogram based on clinical and pathological characteristics to provide a more individualized and accurate estimation of lymph node metastasis (LNM) in patients with early-stage cervical cancer. Methods A total of 7,349 early-stage cervical cancer patients with pathologically confirmed between 1988 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. All the patients were divided into training (n = 5,500) and validation (n = 1,849) cohorts randomly. A cohort of 455 patients from multicenter was used for the external validation. We established a multivariate logistic regression model based on preoperative clinicopathological data, from which a nomogram was developed and validated. A predicted probability of LNM

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3R,5′R)-5-hydroxytalaroflavone (1), talaroisochromenols A–C (3, 5, and 11), (8R,9R,10aR)-5-hydroxyaltenuene (13), (8R,9R,10aS)-5-hydroxyaltenuene (14), (8R,9S,10aR)-5-hydroxyaltenuene (15), nemanecins D and E (25 and 26), 2,5-dimethyl-8-iodochromone (27), and talarofurolactone A (29), together with one new naturally occurring but previously synthesized metabolite, 6-hydroxy-4-methoxycoumarin (28), were isolated and identified from the deep-sea cold-seep-derived fungus Talaromyces sp. CS-258. Among them, racemic ((±)-11) or epimeric (13–15, 25, and 26) mixtures were successfully separated by chiral or gradient elution HPLC. Meanwhile, compound 27 represents a rarely reported naturally occurring iodinated compound. Their planar structures as well as absolute configurations were determined by extensive analysis via NMR, MS, single-crystal X-ray diffraction, Mosher’s method, and ECD or NMR calculation (with DP4+ probability analysis). Possible biosynthetic routes of some isolated compounds, which are related to chromone or isochromone biosynthetic pathways, were put forward. The biological analysis results revealed that compounds 7, 9, 10, 18–22, 24, 30, and 31 showed broad-spectrum antibacterial activities against several human and aquatic pathogens with MIC ranges of 0.5–64 μg/mL.

Tertiary lymphoid structures (TLSs), referred to as tertiary lymphoid organs and lymphoid tissue neogenesis, are aggregates of immune cells that occur in nonlymphoid tissues. In recent years, it has been found that TLSs within the tumor microenvironment have been associated with local adaptive immune immunity against cancer and favorable prognosis in several human solid tumors, including gynecological cancers. The issue of the prognosis of gynecological cancers, including endometrial, cervical, and ovarian cancer, is an enormous challenge that many clinical doctors and researchers are now facing. Concerning the predictive prognostic role of TLSs, effective evaluation, and quantification of TLSs in human tissues may be used to assist gynecologists in assessing the clinical outcome of gynecological cancer patients. This review summarizes the current knowledge of TLSs in gynecological cancers, mainly focusing on the potential mechanism of TLS neogenesis, methods for evaluating TLSs, their prognostic value, and their role in antitumor immune immunity. This review also discusses the new therapeutic methods currently being explored in gynecological cancers to induce the formation of TLSs.

Three new α-pyrone derivatives, annularins L–N (1–3), were isolated from the EtOAc extract of Penicillium herquei MA-370, a fungus obtained from the rhizospheric soil of the mangrove plant Rhizophora mucronata. The planar structures of compounds 1–3 were determined based on comprehensive spectral interpretation of the NMR and MS data. The absolute configuration of 1 was determined by X-ray crystallographic data and that of 2 was assigned by TDDFT calculations of its ECD spectrum and cotton effects comparison with those of 1. The antimicrobial activity of compounds 1–3 was evaluated. [ABSTRACT FROM AUTHOR]

A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 1–6 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 μg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development.

(±)‐Penindolenes A−D (1–4), the first representatives of indole terpenoids featuring a γ‐lactam skeleton, were isolated from the mangrove‐derived endophytic fungus Penicillium brocae MA‐231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ‐lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3‐cleavage of the indole ring to generate two keto groups in 1. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase‐like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids. [ABSTRACT FROM AUTHOR]

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3R,5′R)-5-hydroxytalaroflavone (1), talaroisochromenols A–C (3, 5, and 11), (8R,9R,10aR)-5-hydroxyaltenuene (13), (8R,9R,10aS)-5-hydroxyaltenuene (14), (8R,9S,10aR)-5-hydroxyaltenuene (15), nemanecins D and E (25 and 26), 2,5-dimethyl-8-iodochromone (27), and talarofurolactone A (29), together with one new naturally occurring but previously synthesized metabolite, 6-hydroxy-4-methoxycoumarin (28), were isolated and identified from the deep-sea cold-seep-derived fungus Talaromyces sp. CS-258. Among them, racemic ((±)-11) or epimeric (13–15, 25, and 26) mixtures were successfully separated by chiral or gradient elution HPLC. Meanwhile, compound 27 represents a rarely reported naturally occurring iodinated compound. Their planar structures as well as absolute configurations were determined by extensive analysis via NMR, MS, single-crystal X-ray diffraction, Mosher's method, and ECD or NMR calculation (with DP4+ probability analysis). Possible biosynthetic routes of some isolated compounds, which are related to chromone or isochromone biosynthetic pathways, were put forward. The biological analysis results revealed that compounds 7, 9, 10, 18–22, 24, 30, and 31 showed broad-spectrum antibacterial activities against several human and aquatic pathogens with MIC ranges of 0.5–64 μg/mL. [ABSTRACT FROM AUTHOR]

Five new aromatic polyketides, including a unique benzofuran derivative, talarominine A (1), and four chromone analogs talamins A–D (2–5), along with one known related metabolite, 5-hydroxy-7-methoxy-2,3-dimethylchromone (6), were isolated and identified from the Talaromyces minioluteus CS-138, an endozoic fungus obtained from the deep-sea cold seep mussel Gigantidas platifrons. Their chemical structures were elucidated by detailed analysis of their NMR spectra, HRESIMS and X-ray crystallographic data, and by comparison with literature data as well. The antibacterial and DPPH scavenging activities of compounds 1–6 were evaluated. Compounds 1–3 showed inhibitory activity against some of the tested bacteria whereas compounds 2 and 5 showed potent DPPH radical scavenging activities, which were better than that of the positive control butylated hydroxytoluene (BHT). This work is likely the first report on marine natural products of mussel-derived fungus living in cold seep environments.

An unusual sesquiterpene glycoside trichoacorside A (1) and two novel sorbicillinoid glycosides sorbicillisides A (2) and B (3), together with a known compound sorbicillin (4), were isolated and identified from the culture extract of an endophytic fungus Trichoderma longibrachiatum EN-586, obtained from the marine red alga Laurencia obtusa. Trichoacorside A (1) is the first representative of a glucosamine-coupled acorane-type sesquiterpenoid. Their structures were elucidated based on detailed interpretation of NMR and mass spectroscopic data. The absolute configurations were determined by X-ray crystallographic analysis, chemical derivatization, and DP4+ probability analysis. The antimicrobial activities of compounds 1–4 against several human, aquatic, and plant pathogens were evaluated.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I–M (1–5), which have diverse substitution patterns, and seven known related analogues (6–12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1–3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7β-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.