Nine previously undescribed sesquiterpenoids, bipolarisorokins A–I (1–9); two new xanthones, bipolarithones A and B (10 and 11); two novel sativene-xanthone adducts, bipolarithones C and D (12 and 13); as well as five known compounds (14–1 8) were characterized from the kiwifruit-associated fungus Bipolaris sp. Their structures were elucidated by extensive spectroscopic methods, electronic circular dichroism (ECD), ¹³C NMR calculations, DP4+ probability analyses, and single crystal X-ray diffractions. Many compounds exhibited anti-pathogenic microorganism activity against the bacterium Pseudomonas syringae pv. actinidiae and four pathogenic microorganisms.

Four new polyketides, heterocornol Y (1), stemphyindan (2), pestalospirane C (3), and stemphyspyrane (4), along with five known ones (5–9) were isolated from the endophytic fungus Stemphylium globuliferum 17035 (SG17035) based on the One Strain Many Compounds (OSMAC) strategy allied with an LC-MS approach. These structures were elucidated through extensive spectroscopic analyses, single-crystal X-ray diffraction, and ¹³C NMR-DP4 analysis. Pestalospirane C (3) and stemphyspyrane (4) featured unprecedented spiroketal skeletons. In addition, the putative biosynthetic logic for compounds 1–4 was proposed. Antibacterial and cytotoxic activities of compounds 1–9 were evaluated. Stemphyspyrane (4) displayed promising antibacterial activity against different pathogens, especially against Staphylococcus aureus, Porphyromonas gingivalis, and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 3.125 μM, 6.25 μM, and 12.5 μM, respectively. It is promising as an antibacterial agent for further optimization.

Background and objectives: Muscle relaxation therapy comprising general anesthesia and an intra-articular injection of betamethasone is commonly used to treat capulohumeral periarthritis. This treatment quickly improves the limited motion of the shoulder joint and restores the shoulder to its functional position, but cannot effectively inhibit the inflammatory response. Aseptic inflammatory pain can reportedly be relieved by silver needle acupuncture. However, there is insufficient high-quality evidence to validate the efficacy of silver needle acupuncture in the treatment of capulohumeral periarthritis. Therefore, the proposed study aims to evaluate the efficacy of silver needle acupuncture combined with muscle relaxation therapy in the treatment of capulohumeral periarthritis. Design: A prospective, single-center, open-label, randomized, parallel-controlled trial. Methods: Sixty patients with capulohumeral periarthritis will be assigned to receive either silver needle acupuncture plus muscle relaxation therapy (n = 30) or muscle relaxation therapy alone (n = 30). Patients will be followed up at 3 and 14 days, and 1, 3, 6, and 12 months post-treatment. Outcome measures: The primary outcome measure is a Visual Analog Scale score obtained at 3 days post-treatment. The secondary outcome measures are: the Visual Analog Scale scores before treatment and at 14 days, and 1, 3, 6, and 12 months post-treatment; the Shoulder Joint Activity Function Rating Scale (Melle scale) score, American Shoulder and Elbow Surgeons Standardized Shoulder score, McGill Pain Questionnaire score, University of California at Los Angeles shoulder score before treatment and at 3 and 14 days, and 1, 3, 6, and 12 months post-treatment; 12-item Short-Form Health Survey score at 1, 3, 6, and 12 months post-treatment; and the incidence of adverse events at 3 and 14 days, and 1, 3, 6, and 12 months post-treatment. Conclusion: The study results will provide evidence indicating whether silver needle acupuncture plus muscle relaxation is more effective than muscle relaxation alone in the treatment of capulohumeral periarthritis. We hypothesize that silver needle acupuncture plus muscle relaxation not only improves shoulder joint function, but also reduces inflammatory pain in the shoulder joint. Ethics and dissemination: This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University of China on June 25, 2018 (approval No. QDDXFSYY-LL-06-25). This study will be performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Written informed consent regarding the study protocol and surgery procedure will be obtained from each participant. This study was designed in June 2018. Patient recruitment and data collection began in September 2018 and patient recruitment will end in April 2019. Result analysis will be performed in May 2020. This study will be scheduled to end in June 2020. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Trial registration: This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016706). Study protocol version: 1.0.

α-Ketoglutarate-dependent mononuclear non-haem iron (αKG-NHFe) enzymes are catalytically versatile, yet OkaE is unique for synthesizing azetidine rings via C–C bond formation. Here, we report the unexpected multifunctionality of OkaE, which catalyzes sequential oxidations. Isotopic labelling studies demonstrate that a second O₂ molecule participates in sequential epoxidation and ring cleavage, incorporating two oxygen atoms within a single catalytic cycle to form the previously unknown structure, neuokaramine IV. Crystal structures of the OkaE•Co^II•αKG•okaramine A complex unveil a unique methionine–π interaction network that facilitates substrate binding. Mutational and crystallographic analyses suggest this network fine-tunes substrate orientation relative to the metallo-centre, activating distinct reaction pathways at the 3a-OH or C8a positions. QM/MM simulations indicate that dynamic rotation of the Fe^IV=O species initiates the cycle, enabling reaction bifurcation. This study elucidates the structural and mechanistic basis of OkaE’s reactivity, highlighting its potential as a programmable biocatalyst for natural product diversification.