Nine novel dihydro-α-pyrone derivatives, talaromypyrones A-I (1-9), were isolated from the soil-derived fungus Talaromyces sp. G23. These compounds share a conserved 3'R-configuration within the 4-hydroxy-5,6-dihydro-2-pyrone core but display notable variations in their flanking polyketide chains. Talaromypyrones A-H (1-8) demonstrate potent antibacterial activity against Gram-positive bacteria, including drug-resistant strains, while exhibiting excellent safety profile by showing no cytotoxicity toward normal human LO2 cells. However, they exhibit no activity against Gram-negative bacteria (likely due to their inability to penetrate the outer membrane) and fungi. Such antimicrobial profile, combined with the structural similarity to the α-pyrone antibiotic myxopyronin, suggests a potential target in the switch region of bacterial RNA polymerase (RNAP). Molecular docking studies revealed that talaromypyrone E (5) binds to the same site of RNAP as myxopyronin and forms additional hydrogen bonds between the 4-hydroxy-5,6-dihydro-2-pyrone core and the RNAP residues. Furthermore, talaromypyrones A (1) and D (4) demonstrate moderate anti-inflammatory activity, positioning 4-hydroxy-5,6-dihydro-2-pyrone core as a promising building block for the development of dual-function agents capable of concurrently addressing both conventional and drug-resistant bacterial infections while alleviating associated inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE:Lycopi Herba is a traditional Chinese medicine with blood-activating and stasis-resolving properties, traditionally prescribed to promote diuresis and alleviate edema. These traditional indications are closely related to the pathogenesis of diabetic nephropathy (DN), characterized by renal fibrosis and fluid retention. Although Lycopi Herba has demonstrated potential in treating renal diseases, it remains unclear whether it ameliorates DN by modulating specific inflammatory signaling networks through its multi-component material basis. AIM OF THE STUDY:This study aimed to systematically elucidate the therapeutic efficacy and molecular mechanisms by which the crude extract of Lycopi Herba (LHE) alleviates renal injury and inflammation in DN, employing an integrated strategy of chemical profiling, network pharmacology, and experimental validation. MATERIALS AND METHODS:The chemical profile of LHE was comprehensively characterized using a validated HPLC-DAD-ELSD method. The therapeutic effects of LHE on renal function, histopathology, and inflammatory responses were systematically assessed in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated human podocytes. Evaluations were performed using histopathological staining, ELISA, RT-qPCR, Western blotting, immunofluorescence, and molecular docking. Functional dissection was further conducted to evaluate the contributions of major triterpenoids and flavonoids. RESULTS:In vivo experiments demonstrated that LHE significantly ameliorated renal dysfunction and histopathological injury in DN mice, accompanied by notable reductions in fasting blood glucose and renal pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). In vitro mechanistic studies revealed that LHE specifically blocked the phosphorylation and nuclear translocation of STAT3 and NF-κB, the two core transcription factors of the NF-κB/TNF-α/STAT3 inflammatory axis. This anti-inflammatory effect was achieved via a multi-component synergistic strategy: ten major bioactive compounds were identified in LHE by validated HPLC analysis, among which the highly abundant pentacyclic triterpenoid ursolic acid (UA) exerted direct anti-inflammatory activity by regulating the NF-κB/TNF-α/STAT3 inflammatory axis, serving as the primary material basis for LHE's efficacy. Meanwhile, flavonoids such as quercetin, despite their extremely low abundance in LHE, exhibited extremely potent intrinsic anti-inflammatory activity: at the physiologically equivalent concentration converted from their actual content in LHE, they exerted relatively weak direct modulation of the core inflammatory axis, and mainly exerted their anti-inflammatory effects through other complementary signaling pathways. Together, these bioactive constituents collectively mediated the renoprotective effects of LHE. CONCLUSION:This study demonstrates that LHE ameliorates DN by targeting the NF-κB/TNF-α/STAT3 signaling axis, thereby suppressing renal inflammation through a multi-component combinatorial strategy. These findings validate the ethnopharmacological application of Lycopi Herba and offer new mechanistic insight into its potential as a phytopharmaceutical agent for DN management.

Exploration of the Trichilia connaroides led to the isolation of 16 previously undescribed limonoids (1-16). Compounds 1 and 2 were characterized by polycyclic caged seco-phragmalin frameworks, while 8 possessed a trans-fused B/C ring system. An insect antifeedant bioassay against Spodoptera exigua demonstrated that compounds 2, 11, 12, and 16, at a concentration of 0.005 mg/cm2, exhibited potent antifeedant effects comparable to that of azadirachtin and showed no appreciable cytotoxicity toward murine AML12 hepatocytes.

An investigation of Trichilia connaroides uncovered connarolides A-D (1-4, respectively), four limonoids with exceptional multiring systems. Compound 1 showcased a unique 5/8/6/6-fused ring system distinguished by a bicyclo[5.2.12,4]decane A/B ring framework. Compound 2 featured a 5/8/6/5/6 scaffold incorporating a triply fused furan ring, and a long-conjugated system resulted from 3-deoxygenation. X-ray crystallography established the rare 6/3/6/6/6 ring system of 3. Moreover, 4 was identified as an antioxidant, conferring cytoprotective activity through Nrf2 activation.

Targeted protein degradation has been emerging as a powerful strategy for modulating redox homeostasis. While CRBN-based PROTACs targeting Keap1 successfully promote Nrf2 activation, their translational potential is constrained by CRBN-associated resistance mechanisms and their large molecular size. Two series of hydrophobic tag-tethering degraders (HyTTDs) were designed based on the covalent Keap1 ligand CDDO. Degradation efficiency was evaluated in multiple cell lines, leading to the identification of NBE5, a norbornene-tag-containing degrader, as the most potent compound. NBE5 effectively degraded Keap1 and activated the Nrf2 antioxidant response. Mechanistic studies revealed a unique dual-pathway degradation process involving the ubiquitin-proteasome system and the autophagy-lysosome pathway. Our findings not only establish HyTTD as a viable degradation strategy for Keap1 but also identify NBE5 as a promising therapeutic candidate for redox-related pathologies such as inflammatory bowel disease.

KRAS mutation results in higher proliferation rates and miserable prognosis of cancers. Targeting the interaction between KRAS and PDE6D provided an alternative strategy to overcome KRAS-mutant pancreatic cancers. Gaudichaudione H (GH) is a prenylated caged xanthone isolated from Garcinia oligantha. In this work, GH was selected as a potential anti-cancer compound by MTT screening of twelve prenylated xanthonoids from G. oligantha. Further studies demonstrated that GH inhibited proliferation of a panel of cancer cell lines and induced pancreatic cancer cell apoptosis. GH suppressed xenograft tumor growth accompanied with decreased phosphorylation of ERK and AKT. Binding with PDEδ and thus interfering the KRAS-PDEδ interaction was verified as the possible mechanism of GH. These findings implicated GH as a promising candidate for the treatment of pancreatic cancers with KRAS mutation, provided novel insight into the underlying mechanisms of GH-induced anticancer effects.

Introduction: Chronic obstructive pulmonary disease (COPD) represents a significant global health challenge, characterized by substantial morbidity and mortality rates. In traditional Chinese medicine (TCM), Farfarae Flos (FF) has been widely utilized as a therapeutic agent for COPD. However, its specific bioactive compounds and the underlying mechanisms are unclear. Objectives: This study aims to identify bioactive constituent of FF against COPD and illustrate its therapeutic target and mechanism. Methods and results: In this research, a high-throughput screening on constituents of FF was conducted, leading to the identification of a potent anti-COPD lead, tussilagone (TUS). Utilizing biotin-labeling approach, Kelch-like ECH-associated protein 1 (KEAP1), the ubiquitin E3 ligase of nuclear factor erythroid 2-related factor 2 (Nrf2), was identified to be the direct target of TUS. Mechanistically, TUS activated KEAP1-Nrf2 axis by covalent modification of cysteine 434 (Cys434), a novel high-reactivity cysteine of KEAP1. TUS-mediated Nrf2 activation further suppressed the activation of nuclear factor kappa-B (NF-κB) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, consequently attenuating lung inflammation in COPD. Conclusion: TUS was identified as the bioactive constituent of FF against COPD, which directly targeted Cys434 of KEAP1. KEAP1 was proven to be a pharmacological target for the treatment of COPD, and Cys434 was identified to be the first highly reactive cysteine in Kelch domain of KEAP1. TUS inhibits lung inflammation by regulating Nrf2 and NF-κB/NLRP3, which is the mechanism of FF against COPD.

Background Inflammation can result in the development of breast cancer in women with overweight and obese, and also affects the outcome and prognosis of breast cancer patients, thereby decreasing the cure and survival rates of breast cancer patients. Exercise may benefit breast cancer patients as a supplement to conventional treatments. However, research on the effects of exercise on inflammatory markers in women with breast cancer who are overweight and obese remains incomplete. Objective A systematic review and meta-analysis were used to study the effects of exercise on inflammatory markers in women with breast cancer who are overweight and obese. Method Literature up to May 2024 was searched from databases such as Cochrane, Embase, Pubmed, Web of Science, and EBSCO, and English-language randomized controlled trials (RCTs) that met the inclusion criteria were screened. The screening criteria were as follows (A) written in English; (B) RCT; (C) studied in women with overweight obese and breast cancer; (D) outcome measures: inflammatory markers; (E) the duration of the exercise intervention was unlimited. Results A total of 14 articles and 1064 participants were included. Exercise significantly reduced C-reactive protein (CRP) (MD: -0.52, 95 % CI: -0.94 to -0.11; p = 0.01; heterogeneity p < 0.1), interleukin-6 (IL-6) (MD: -0.87, 95 % CI: -1.62 to -0.11; p = 0.02; heterogeneity p < 0.1), and leptin (MD: -0.92, 95 % CI: -1.71 to -0.13; p = 0.02; heterogeneity p < 0.1) levels and exercise significantly increased adiponectin levels (MD: 0.89, 95 % CI: 0.03-1.75, p = 0.04; heterogeneity p < 0.1) but had no effect on tumor necrosis factor-alpha (TNF-alpha) (MD: -0.26, 95 % CI: -0.82-0.29; p = 0.35; heterogeneity p < 0.1) and IL-10 (MD: 0.14, 95 % CI: -0.17-0.45; p = 0.37; heterogeneity p = 0.45) were not significant. In addition, subgroup analyses suggest that combination training (CE) may be the most recommended type of exercise to decrease pro-inflammatory markers, and increase anti-inflammatory markers in women with overweight obesity, and have breast cancer. Conclusion Exercise significantly reduced CRP, IL-6, and leptin levels and overall increased adiponectin levels in women with overweight obese, and breast cancer. However, the effects on TNF-alpha and IL-10 levels were not significant. CE may be the most recommended type of exercise for reducing pro-inflammatory factors and increasing anti-inflammatory factors. Therefore, this study considers exercise as an effective complementary approach to managing inflammatory markers in women with breast cancer who are overweight and obese. Future researchers may consider exploring the combined effects of exercise and dietary control, weight loss, and other factors, and formulate a comprehensive treatment plan accordingly.

Background: Doxorubicin (DOX), a classical chemotherapeutic agent, faces significant limitations because of its well-documented risk of inducing cardiotoxicity. Effective prevention of DOX-induced cardiotoxicity is urgently needed. Given that alterations in metabolic pathways have been observed in both cardiovascular diseases and cancer, targeting specific metabolic pathways may offer dual benefits by mitigating DOX-induced cardiotoxicity while simultaneously enhancing its antitumor efficacy. Objectives: This study sought to explore the characteristic metabolic alterations associated with early DOX-induced cardiotoxicity and identify a therapeutic target that simultaneously inhibits cancer and protects the myocardium. Methods: Metabolomic and transcriptomic analyses were performed on heart tissues from murine models of DOX-induced cardiotoxicity to identify the most significantly altered metabolic pathway. The most altered metabolite involved in the candidate pathway was chosen and verified in both mice and humans. The protective effects of the chosen metabolite against DOX-induced cardiotoxicity and its antitumor effects were evaluated. Potential mechanisms were explored using C57BL/6J mice, OPLAH global knockout mice, BALB/c nude mice and NSG mice. Results: The glutathione metabolic pathway was identified as the most altered pathway in heart tissues with DOX-induced cardiotoxicity. The 5-oxoproline/OPLAH (5-oxoprolinase) axis was the most critical node. Downregulation of 5-oxoproline was observed in serum samples from both humans and mice. Exogenous 5-oxoproline supplementation effectively restored myocardial 5-oxoproline levels, subsequently mitigating DOX-induced cardiac dysfunction. Interestingly, we observed an additional inhibitory effect of 5-oxoproline on tumor proliferation in tumor-bearing mice treated with DOX. Mechanistically, 5-oxoproline exerts its cardioprotective effects by restoring glutathione metabolic homeostasis through the modulation of its downstream enzyme OPLAH while simultaneously suppressing tumor proliferation by inhibiting its upstream enzyme, gamma-glutamyl cyclotransferase (GGCT). Conclusions: This study reveals a previously unrecognized dual role of 5-oxoproline, which functions both as an early biomarker for DOX-induced cardiotoxicity detection and as a therapeutic target that simultaneously inhibits cancer growth and protects the myocardium.

Four novel secophragmalin-type limonoids, triconnarins A-D (1-4), have been identified from the small branches and leaves of Trichilia connaroides. Triconnarin A (1) featured an unprecedented 5/6/4/6/6 ring skeleton, which belonged to the rare 1,10-secophragmalin classes. Triconnarin B (2) was the first B-ring opening secophragmalin limonoid, whereas triconnarin C (3) possessed a unique 5/5-6/6 ring system. Compounds 1-3 were proven to demonstrate potent QR-inducing activity.

Two pairs of enantiomers of biphenyl dimers, garciyndiphenyls A and B [(±)-1 and (±)-2], were isolated from Garcinia yunnanensis. These compounds represent the first example of a complex polycyclic caged skeleton of biphenyl dimers. Their structures and absolute configurations were determined through comprehensive spectroscopic analysis, X-ray crystallography, and electronic circular dichroism (ECD) calculations. Additionally, plausible biosynthetic routes for compounds 1 and 2 were proposed. Both compounds exhibited potential antimigration and anti-invasion effects in human lung cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE:Thesium chinense Turcz., a traditional Chinese herbal medicine, displays good therapeutic efficiency against respiratory diseases (e.g. pneumonia, pharyngitis) in clinical applications, however, its effects on COPD and the mechanism of action are still unclear. AIM OF THE STUDY:This study aims to investigate the therapeutic effect of the ethyl acetate fraction of Thesium chinense Turcz. (TCEA) on COPD and reveal the underlying mechanism. MATERIALS AND METHODS:A cigarette smoke (CS)-induced mouse COPD model was established, and the efficacy of TCEA was evaluated using peripheral blood testing, HE and Masson staining, qRT-PCR and ELISA assays. TCEA was analyzed for chemical composition by LC-MS/MS and HPLC. Prediction of major signaling pathways and potential targets was performed by network pharmacology. The molecular mechanism of TCEA was explored by immunoblotting, immunofluorescence staining, flow cytometry, and ubiquitination assay. Finally, potential active small molecules in TCEA were identified by molecular virtual screening. RESULTS:TCEA treatment significantly inhibited the secretion of pro-inflammatory factors and attenuated pathological emphysema. The main chemical constituents of TCEA were identified as flavonoids by UPLC-MS/MS. Network pharmacology analysis enriched the Nrf2 signaling pathway closely related to oxidative stress. Our results suggested that TCEA inhibited ferroptosis by activating Nrf2/SLC7A11/GPX4 axis and inhibiting lipid metabolism-related proteins, ACSL4, ALOX5 and COX2 in vivo and in vitro. Noteworthily, the beneficial impact of TCEA on regulation of SLC7A11 and GPX4 vanished after silencing Nrf2. Moreover, Nrf2 ubiquitination was inhibited by TCEA treatment. Finally, several flavonoids modulating Nrf2 were identified by molecular virtual screening. CONCLUSIONS:TCEA significantly alleviated COPD progression by inhibiting ferroptosis primarily through activation of Nrf2/SLC7A11/GPX4 signaling. Flavonoids are the main active components that exert their effects. These findings shed light on the mechanism of action of TCEA and its potential active components, providing a feasible approach for the treatment of COPD.

Physalis Calyx seu Fructus (PCF) is frequently prescribed for treating inflammation-related respiratory diseases in traditional Chinese medicine. The aim of the study is to identify the active partitions of PCF against inflammation-related respiratory diseases and explore their therapeutic effects and mechanisms. In the present study, two active partitions, 50-EFP-2 and 70-EFP, were obtained through anti-inflammatory bioactivity-guided enrichment of macroporous resin. These two partitions at 10 mg/kg potently alleviated lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) and ovalbumin (OVA)-induced asthma in mice. Phytochemical investigation was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and high-performance LC (HPLC), and indicated that withanolides are the predominant constituents of these two partitions. Moreover, their potential targets were predicted by network pharmacological analysis, which showed that withanolides in PCF mainly attenuated ALI and asthma by regulating nuclear factor-κB (NF-κB) to inhibit inflammatory response. 50-EFP-2 and 70-EFP inhibited inflammation and oxidative stress by regulating NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2), both in vivo and in vitro. Collectively, two partitions rich in withanolides were discovered from PCF, which potently alleviated ALI and asthma by regulating Nrf2 and NF-κB pathways. These findings provide the foundation for discovering withanolide-type leading compounds and developing novel therapeutics against inflammation-related respiratory diseases.

Descurainiae Semen Lepidii Semen, the seed of Descurainia Sophia (L.) Webb. ex Prantl. or Lepidium apetalum Willd. known as "Tinglizi" in Chinese is one of the most commonly used Chinese medicines for respiratory diseases. And it is also widely used to treat multiple diseases in Iran, India, Korea, Japan, and other countries. At present, more than 200 chemical compounds have been revealed from Descurainiae Semen Lepidii Semen. Modern pharmacological studies show that Descurainiae Semen Lepidii Semen has great potential for treating pulmonary diseases, cardiovascular system diseases, and kidney diseases. Moreover, Descurainiae Semen is also of great potential as a health food and green pesticide. Pharmacological studies have demonstrated the traditional uses of Descurainiae Semen Lepidii Semen, especially in pulmonary disease and the heart problems caused by pulmonary disease, while the correlation between various pharmacological effects and various types of ingredients still needs to be confirmed by research. More than 200 compounds have been isolated from Descurainiae Semen Lepidii Semen, but steroidal compounds with cardiotonic activity and the characteristic components of glucosinolates have not been studied deeply and need further study. Besides, the similarity in compounds indicates the rationality of using Descurainiae Semen and Lepidii Semen as the same traditional Chinese medicine. But a more systematic comparative study of compositions and pharmacological effects of Descurainiae Semen and Lepidii Semen is very necessary to explain the reasons for the difference in clinical application. This paper aimed to lay a foundation and provide a reference for the follow-up research and wide application of Descurainia sophia and Lepidium apetalum.

INTRODUCTION:Kelch ECH-associating protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) axis is crucial for regulating oxidative stress and inflammatory responses in acute pneumonia. Sphaeropsidin A (SA) is a antioxidant diterpenoid isolated from Sphaeropsis sapinea f. sp. cupressi, discovered as a novel Nrf2 agonist by our research group previously. However, the accurate function and mechanism of SA in treating acute pneumonia are still unknown. METHODS:The therapeutic effect of SA was evaluated in LPS-induced acute pneumonia in mice. The underlying mechanism of action was then analyzed by transcriptomics. The direct target of SA was identified through the synthesis of SA-biotin probe, and the binding amino acid residues were found and verified by LC-MS/MS analysis and site-specific mutation. Finally, knockout mice were employed to verify the mechanism of SA. RESULTS:Our data indicated that SA significantly inhibited LPS-induced acute pneumonia in mice via up-regulating Nrf2, inhibiting NLRP3 inflammasome and NF-κB activation, and identified Keap1 as the direct target of SA. Specifically, the effective dose of SA in mice was only 2 mg/kg. SA selectively covalent bound to Keap1 in cysteine 151 residue (Cys151). SA mediated the activation of Nrf2 and reduced the level of ROS, thereby inhibiting the NF-κB and NLRP3 inflammasome. Besides, SA formed hydrogen bond with ASP48 of ASC, blocking its oligomerization and inhibiting the activation of NLRP3 inflammasome. CONCLUSION:This study indicates that SA might be a new covalent molecule of Keap1 to activate Nrf2, and is a promising drug candidate or lead molecule for the therapy of acute pneumonia through regulating Nrf2/NF-κB/NLRP3 inflammasome axis.

TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems. Here the authors report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host: they see that the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. They show that TnpB can be harnessed for flexible single-nucleotide editing with templated repair.

Diabetic nephropathy (DN) poses a significant risk to individuals with diabetes. Inflammation plays a crucial role in DN pathogenesis. Lycorine hydrochloride (LH) is derived from Lycoris radiata (L'Hér.). This herb has been identified as a potent anti-inflammatory molecule. Further studies indicated that LH displayed therapeutic potential against metabolic disorders, renal dysfunction, and fibrosis in a high-fat diet and streptozotocin-induced (HFD/STZ)-induced DN mouse model. Mechanistically, LH mitigated renal inflammation in DN mice by targeting NF-κB pathways and the NLRP3 inflammasome verified by in vivo study. In vitro, LH inhibited NLRP3 inflammasome activation induced by nigericin (Ng), monosodium urate (MSU), and ATP, reduced caspase-1 activation, and IL-1β release. Additionally, LH suppressed the NF-κB IS-induced activation, prevented nuclear translocation of NF-κB, and subsequently reduced the expression of downstream proteins COX2 and iNOS. Collectively, these results indicated that LH primarily improved hyperglycemia-induced renal function by reducing inflammation by targeting NF-κB and NLRP3 inflammasome, implying it is a promising therapeutic agent for DN.

Cumulative evidence has verified that persistent oxidative stress is involved in the development of various chronic diseases, including pulmonary, neurodegenerative, kidney, cardiovascular, and liver diseases, as well as cancers. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in regulating cellular oxidative stress and inflammatory reactions, making it a focal point for disease prevention and treatment strategies. Natural products are essential resources for discovering leading molecules for new drug research and development. In this review, we comprehensively outlined the progression of the knowledge on the Nrf2 pathway, Nrf2 activators in clinical trials, the naturally-derived Nrf2 modulators (particularly from 2014-present), as well as their effects on the pathogenesis of chronic diseases.

Covalent organic frameworks (COFs) show promising prospect as the photocatalysts with advantages of exceptional light adsorption capabilities, large specific surface area, and adjustable band structure. However, COFs usually suffer from severe recombination of photogenerated carriers. Therefore, there is an urgent need to design effective COF-based heterostructures to enhance the separation of carriers. In this work, a porphyrin-based COF with electron donor-acceptor structure is synthesized via condensation polymerization by using 5, 10, 15, 20-tetrakis (4-aminophenyl) porphyrin (TAPPP) and N, N, N, N-tetra(4-aldehydephenyl)-1, 4-phenylenediamine as the electron donor and acceptor, respectively. Subsequently, ZnIn2S4 (ZIS) are successfully in-situ grown on the surface of porphyrin-based COF, forming a novel core-shell structure. The in-situ synthesized ZIS with positive charges can be easily adsorbed on the negatively charged sites of the COF’s surface via the electrostatic interaction. This organic/inorganic hybrid COF-ZIS heterostructure exhibits a superior photocatalytic hydrogen evolution (PHE) rate of 695 μmol g−1 h−1, approximately three times higher than that of ZIS. The construction of COF-ZIS heterostructure played an important role in enhancing the separation and transport of photogenerated carriers, which provided more electrons at the surface of ZIS to take part in proton reduction. Electron paramagnetic resonance spectra confirm the charge carriers transfer mode in the COF-ZIS heterostructure via an S-scheme mechanism. Moreover, upon loading Pt as the cocatalyst, the heterostructure achieves an effective PHE rate of 2711 μmol g−1 h−1 along with an exceptional stability. Additionally, the COF-ZIS heterostructure reaches up to 2.45% of apparent quantum efficiency at 400nm. Notably, the average lifetime of the COF-ZIS heterostructure increases by 43.2% and 98.9% compared to that of ZIS and COF individually, as observed through single-particle fluorescence spectroscopy. This work gives valuable inspiration into the building of donor-acceptor COF-based S-scheme heterostructures to achieve highly effective green energy conversion by aligning band structures.

Triterpene skeletons, catalyzing by 2,3-oxidosqualene cyclases (OSCs), are essential for synthesis of steroids and triterpenoids. In japonica rice cultivars Zhonghua11, a total of 12 OsOSCs have been found. While the catalytic functions of OsOSC1, 3, 4, 9, and 10 remain unclear, the functions of the other OsOSCs have been well studied. In this study, we conducted a comprehensive analysis of 12 OSC genes within genus Oryza with the aid of 63 genomes from cultivated and wild rice. We found that OSC genes are relatively conserved within genus Oryza with a few exceptions. Collinearity analysis further suggested that, throughout the evolutionary history of genus Oryza, the OSC genes have not undergone significant rearrangements or losses. Further functional analysis of 5 uncharacterized OSCs revealed that OsOSC10 was a friedelin synthase, which affected the development of rice grains. Additionally, the reconstructed ancestral sequences of Oryza OSC3 and Oryza OSC9 had lupeol synthase and poaceatapetol synthase activity, respectively. The discovery of friedelin synthase in rice unlocks a new catalytic path and biological function of OsOSC10. The pan-genome analysis of OSCs within genus Oryza gives insights into the evolutionary trajectory and products diversity of Oryza OSCs.