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Objective: This study assesses the safety and efficacy of tirofiban for patients with large vessel occlusion stroke after intravenous thrombolysis., Methods: This study data was from SUSTAIN, DEVT, and RESCUE BT trials. According to whether the use of tirofiban who underwent endovascular treatment and preceding intravenous thrombolysis was divided into the tirofiban group and the no-tirofiban group. The safety outcomes were symptomatic intracranial hemorrhage, any intracranial hemorrhage within 48 h, and 3-month mortality. The efficacy outcome was defined as a score of 0-2 on the modified Rankin Scale scores at 3 months., Results: A total of 372 patients with intravenous thrombolysis were included in these SUSTAIN, DEVT, and RESCUE BT trials. Adjusted multivariate analysis showed that tirofiban with intravenous thrombolysis was not associated with symptomatic intracranial hemorrhage (aOR, 0.87; 95 % CI, 0.49-1.57; P=0.65), any intracranial hemorrhage within 48 h (aOR, 1.00; 95 % CI, 0.60-1.66; P=1.00), 3-month mortality (aOR, 1.10; 95 % CI, 0.56-2.19; P=0.78) and 3-month modified Rankin Scale scores 0-2 (aOR, 0.72; 95 % CI, 0.42-1.25; P=0.25) in patients with acute large vessel occlusion. In the subgroup analysis, we found that tirofiban was not recommended for females (aOR, 0.34; 95 % CI, 0.12-0.93), baseline Alberta Stroke Program Early CT Score≤9 (aOR, 0.37; 95 % CI, 0.18-0.76), and cardiogenic embolism (aOR, 0.36; 95 % CI, 0.14-0.97)., Conclusion: Tirofiban combined with intravenous thrombolysis in patients with acute large vessel occlusion may be safe. Further studies need to confirm the effectiveness of tirofiban after intravenous thrombolysis in different stroke etiology., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment., Methods: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986., Findings: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly., Interpretation: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment., Funding: Stryker and Amsterdam University Medical Centers, University of Amsterdam., Competing Interests: Declaration of interests CBM reports grants from CardioVasculair Onderzoek Nederland by the Dutch Heart Foundation, TWIN Foundation, the European Commission, Healthcare Evaluation Netherlands, and Stryker (all paid to institution); and is a minority interest shareholder of Nicolab. YBR reports being a minor shareholder of Nicolab. JG reports consultancy funds from Medtronic as Global Principal Investigator of STAR (NCT01327989) and Swift Direct (NCT03192332) and from Cerenovus (now part of Johnson & Johnson) and participation on a data safety monitoring board or advisory board (clinical ethics committee member of the Promise Study) for Penumbra. CC reports consulting fees from Microvention, Medtronic, Cerenovus, MIVI, and Stryker. TD reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Microvention. BJE reports institutional funding from HealthHolland Top Sector Life Sciences and Nicolab. RGN reports funding from Cerenovus as Principal Investigator of the ENDOLOW trial and from Stryker Neurovascular as Principal Investigator of the DUSK trial; consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze; and being an investor in Viz-AI, Perfuze, Cerebrotech, Reist–Q’Apel Medical, Truvic, Vastrax, and Viseon. UF reports funding from Medtronic, Stryker, Rapid Medical, Phenox, Penumbra, Swiss National Science Foundation, CSL Behring, Portola (now part of Alexion), Boehringer Ingelheim, and Biogen. SD reports institutional funding from the National Health and Medical Research Council and funding from Medtronic, Abbott, and CSL Behring for participation on data safety monitoring boards or advisory boards. PM reports institutional funding from Stryker and Medtronic. BY reports institutional research grants from Stryker and Medtronic. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Due to their distinctive physical, chemical, electrical, and optical properties as well as their prospective uses, 2D covalent organic framework (COF) have attracted much attention. Herein, TaTPA-COF was effectively synthesized from the condensation of TTA and TFPA using a facile solvothermal method and characterized by SEM image, FT-IR spectra, and PXRD pattern. The generated bulk TaTPA-COF materials combined with DNA aptamers are utilized as the acceptor (quencher) for the highly sensitive and selective detection of adenosine 5'-triphosphate (ATP) and thrombin, with a novel fluorescence biosensing platform and a proof-of-concept application., 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.)

Fifteen secondary metabolites, including five new sesquiterpenoids (1-5), one new benzofuranoid (10), one new ophiobolin sesterterpenoid (11), and one new 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoid (15), as well as seven known analogues (6-9 and 12-14), were isolated and characterized from fungus Aspergillus calidoustus, which was separated from the wetland soil collected at Dianchi Lake, Yunnan Province. Compound 5 featured an unusual dioxolane moiety, and compound 15 was a rare austin meroterpenoid analogue with the opened A ring, and also featured an undescribed oxygen bridge between C-3 and C-16 to construct an unexpected tetrahydrofuran ring. Their structures were established by widespread spectroscopic methods, single-crystal X-ray diffraction experiments, and ECD calculation. All the isolated drimane sesquiterpenoids were evaluated for the in vitro cytotoxicity against five tumor cell lines, including SW480 (colon cancer), IOMM-Lee (meningioma), HeLa (cervical cancer), FARAGE (diffuse large B-cell lymphoma), and SU-DHL-4 (diffuse large B-cell lymphoma). Compound 9 exhibited significant cytotoxicity against FARAGE and SU-DHL-4 tumor cell lines with IC 50 values of 5.54 and 9.78 μM, respectively. Further mechanism study showed that 9 could significantly promote apoptosis in FARAGE and SU-DHL-4 cell lines by interfering with mitochondrial function., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Three pairs of undescribed enantiomeric α-pyrone derivatives (1a/1b-3a/3b) and six undescribed congeners (4-9), were obtained from the fungus Alternaria brassicicola that was isolated from the fresh leaves of Siegesbeckia pubescens Makino (Compositae). The structures of these new compounds were characterized by extensive NMR spectroscopic and HRESIMS data, and their absolute configurations were further elucidated by a modified Mosher's method, chemical conversion, single-crystal X-ray diffraction analysis, and ECD calculations. This is the first report of three pairs of enantiomeric α-pyrone derivatives from the fungus A. brassicicola, and these enantiomers were successfully acquired from scalemic mixtures via chiral HPLC. Compounds 1a/1b-3a/3b and 4-9 were evaluated for the herbicidal activity against Echinochloa crusgalli, Setaria viridis, Portulaca oleracea, and Taraxacum mongolicum. At a concentration of 100 μg/mL, compounds 1a and 1b could significantly inhibit the germination of monocotyledon weed seeds (E. crusgalli and S. viridis) with inhibitory ratios ranging from 68.6 ± 6.4% to 84.2 ± 5.1%, which was equivalent to that of the positive control (glyphosate). The potential structure-herbicidal activity relationship of these compounds was also discussed. To a certain extent, the results of this study will attract great interest for the potential practical application of promising fungal metabolites, α-pyrone derivatives, as ecofriendly herbicides., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Large-scale culture is a complementary and practical method for genome mining and OSMAC approaches to discover novel natural products through accumulation and reprocessing effects. By employing a large-scale culture approach, twelve 3,5-dimethylorsellinic acid (DMOA)-based meroterpenoids, including five undescribed compounds, namely asperanstinoids A-E, were obtained from fungus Aspergillus calidoustus, which was isolated from the wetland soil collected at Dianchi Lake, Yunnan Province. The structures and absolute configurations of asperanstinoids A-E were determined by various spectroscopic analyses, including NMR spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations, and the absolute configurations of three known compounds, dehydroaustinol, austinol, and austin, were confirmed via single-crystal X-ray diffraction for the first time. Notably, asperanstinoid A represents the second example of a DMOA-based meroterpenoid featuring a unique 6/5/6/6/6/5-fused hexacyclic skeleton with a rare "1,13-epoxy" moiety. The cytotoxicity assay of all these isolates revealed that asperanstinoid D, dehydroaustinol, and austin displayed considerable cytotoxicity against the HL-60 and SU-DHL-4 tumor cell lines with IC 50 values ranging from 15.7 to 27.8 μM., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Five new acetylenic phenol derivatives (1-4 and 7), one new benzofuran derivative (8), one new naphthol derivative (9), and two known analogues (5 and 6), were isolated and identified from an endophytic fungus Daldinia sp. TJ403-LS1 that was isolated from the medicinally valuable plant Anoectochilus roxburghii. Their structures were elucidated by means of extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. In addition, compound 1 exhibited remarkable immunosuppressive activity against LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with the same IC 50 values of 0.06 μM and BChE inhibitory activity with an IC 50 value of 6.93 ± 0.71 μM, and compounds 6, 8 and 9 showed excellent BChE inhibitory activity with IC 50 values of 16.00 ± 0.30, 23.33 ± 0.55, and 15.53 ± 0.39 μM, respectively (positive drug neostigmine, IC 50  = 49.60 ± 6.10 μM), highlighting the promising potentials to be designed and developed as immunosuppressive and BChE inhibitory agents., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Coculturing two or more fungi is a useful strategy to awaken the silent genes to produce structurally diverse and bioactive natural products. Through the coculture of Pestalotiopsis sp. and Penicillium bialowiezense, six new isoprenylated chromane derivatives, including two pairs of enantiomeric ones (1a/1b-2a/2b) and two optical pure ones (3-4), two new isoprenylated phenol glucoside derivatives (6-7), as well as eight known structural analogues (5 and 8-14), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray crystallography, and ECD calculation. The Δ 10,11 double bond of pestaloficin D (5) was revised to E-configurated based on the extensive spectroscopic analyses. Compounds 1a/1b and 2a/2b were the first examples of enantiomeric isoprenylated chromane derivatives, which were successfully separated by chiral HPLC. Additionally, all the isolated compounds were evaluated for the in vitro β-glucuronidase (GUS) and butyrylcholinesterase (BChE) inhibitory activities. Compounds 1a and 1b showed significant β-glucuronidase inhibitory potency with IC 50 values of 7.6 and 10.3 μM, respectively. Compound 14 exhibited moderate BChE inhibitory activity with an IC 50 value of 21.3 μM. In addition, the structure-enzyme inhibitory activity relationship of compounds 1-14 is discussed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fusicoccane-derived diterpenoids bearing a unique bridgehead double-bond-containing tricyclo[9.2.1.0 3,7 ]tetradecane (5-9-5 ring system) core skeleton represent a rarely reported class of rearranged terpenoids, which traced back to fusicoccanes with a classical dicyclopenta[a,d]cyclooctane (5-8-5 ring system) core skeleton via a crucial Wagner-Meerwein rearrangement reaction. In this research, alterbrassicenes B-D (1-3), three new rearranged fusicoccane diterpenoids bearing a rare bridgehead double-bond-containing tricyclo[9.2.1.0 3,7 ]tetradecane core skeleton, together with two known congeners, brassicicenes O and K (4 and 5), were isolated from the modified cultures of fungus Alternaria brassicicola. Their structures were elucidated by comprehensive analyses of the NMR and HRESIMS data, and the absolute configurations of 1 and 4 were further confirmed via a combination of 13 C NMR and ECD calculations and single-crystal X-ray diffraction analysis (Cu Kα). Interestingly, alterbrassicene B (1) represented the second case of bridgehead C-10-C-11 double-bond-containing natural products with a bicyclo[6.2.1]undecane core skeleton, and also featured an undescribed oxygen bridge between C-6 and C-14 to construct an unprecedentedly caged tetracyclic system. Alterbrassicenes B-D showed moderate cytotoxic activity against certain human tumor cell lines with IC 50 values in the range of 15.87-36.85 μM., 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 © 2020 Elsevier Inc. All rights reserved.)

Seven undescribed alkaloids, namely fischeramides A and B, 5,6-dimethoxycircumdatin C, 6-hydroxyacetylaszonalenin, 3-methoxyglyantrypine, 9-methoxyfumitremorgin C, and spirotryprostatin M, one undescribed natural product, namely 11-deacetyl pyripyropene A, together with nine known congeners, were isolated from the solid cultures of fungus Neosartorya fischeri, which was separated from a medicinal insect Cryptotympana atrata. Their structures were elucidated by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analyses. Structurally, fischeramides A and B represented a pair of rare geometric isomers of the benzodiazepinedione derivatives with a highly conjugated feature. Fischeramide A showed potential immunosuppressive activity in LPS and anti-CD3/anti-CD28 mAbs activated murine splenocytes proliferation with IC 50 values of 7.08 and 6.31 μM, respectively, and also showed anti-inflammatory activity against the lipopolysaccharide-induced nitric oxide production with an IC 50 value of 25 ± 1 μM. In addition, 5,6-dimethoxycircumdatin C showed remarkable antibacterial activity against ESBL-producing E. coli with an MIC value of 2.0 μg/mL., 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 © 2020 Elsevier Ltd. All rights reserved.)

Currently, 5-fluorouracil (5-FU) resistance became a major obstacle to its clinical use for patients with hepatocellular carcinoma (HCC). It's urgent to develop a novel strategy for enhancing the therapeutic efficacy of 5-FU. Herein, we found that H1 (a derivative of Tetrandrine) exerted a potent anti-MDR effect on growth of 5-FU resistant HCC cells (Bel7402/5FU). The resistant fold (RF) of 5-FU is over 160-fold, while the RF of H1 is only 4.8-fold in Bel7402/5-FU cells. Further studies demonstrated that blockage of STAT3/MCL-1 signaling and induction of PUMA is responsible to anti-MDR activity of H1. Moreover, combination of H1 and 5-FU (Ratio = 1:2) could synergistically induce apoptosis of Bel7402/5-FU cells. Co-treatment of H1 enhances the suppression of p-STAT3 and MCL-1, and significantly increases PUMA expression. Finally, the combination of H1 and 5-FU results in an increase of cleaved PARP. Taken together, H1 effectively improve the cytotoxic effect of 5-FU against Bel7402/5-FU cells via blocking STAT3/MCL-1 pathway and inducing PUMA. Our findings suggested that combination 5-FU with anti-MDR agents might present a novel strategy to enhance the therapeutic efficacy of 5-FU in resistant HCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Seven previously undescribed metabolites, designated as tricycloalternarenes Q-W (1-7), were isolated and identified from the fermented rice substrate of fungus Alternaria brassicicola. The planar and absolute structures of all new compounds were determined on the basis of extensive NMR spectroscopic data, a modified Mosher's method, X-ray crystallographic analysis, and electronic circular dichroism (ECD) spectral analyses. All the isolates were evaluated for in vitro cytotoxicity against five human tumor MM231, MM468, HeLa, SW1990, and SW480 cell lines, and compounds 1, 2, 5, and 7 showed selective cytotoxicity against certain human tumor cell lines with IC 50 values ranging from 12.83 to 32.87 μM, with no obvious cytotoxicity to the normal LO2 cell., (Copyright © 2019 Elsevier Inc. All rights reserved.)

By feeding 1-methyl-l-tryptophan (1-MT) into cultures of the arthropod-associated fungus Chaetomium globosum TW1-1, three novel cytochalasan alkaloids, termed as armochaetoglosins A-C (1-3), together with five known analogues, namely prochaetoglobosin I (4), chaetoglobosin T (5), chaetoglobosin C (6), armochaetoglobin Y (7), and chaetoglobosin V b (8), were isolated and characterized. Their structures including absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray crystallography, and comparison of the experimental electronic circular dichroism (ECD) spectra. Structurally, compounds 1-3 represented the first examples of 1'-N-methyl-chaetoglobosins, which were possibly biosynthesized from the additive 1-MT rather than tryptophan. Additionally, compound 3 showed the highest antibacterial activity against K. pneumoniae and ESBL-E. coli with MIC values of 4.0 μg/mL and 16.0 μg/mL, respectively, wherein the inhibitory effect of 3 against K. pneumoniae was stronger than that of the clinically used antibiotic meropenem, with an MIC value of 8 μg/mL. Our findings may provide new chemical templates for the development of new antibacterial agents against drug-resistant microbial pathogens., (Copyright © 2018 Elsevier Inc. All rights reserved.)

By feeding L-tyrosine into the culture medium, nine undescribed compounds, termed as armochaetoglasins A-I, together with three known analogues, namely armochaetoglobin E, chaetoglobosin V, and chaetoglobosin J, were isolated and identified from the medicinal terrestrial arthropod-derived fungus Chaetomium globosum TW1-1. Their structures were elucidated by means of NMR spectroscopy, single-crystal X-ray crystallography, and comparison of their electronic circular dichroism (ECD) spectra. Structurally, armochaetoglasin A represented the first tyrosine-derived cytochalasan alkaloid characterized by a 13-membered carbocyclic ring system; armochaetoglasins B and C possessed a rare 19,20-seco-chaetoglobosin skeleton. Armochaetoglasin B, chaetoglobosin V, and chaetoglobosin J showed weak cytotoxic activity with IC 50 values ranging from 19.5 to 34.72 μM., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Three new compounds, including a prenylated tryptophan derivative, luteoride E (1), a butenolide derivative, versicolactone G (2), and a linear aliphatic alcohol, (3E,7E)-4,8-dimethyl-undecane-3,7-diene-1,11-diol (3), together with nine known compounds (4-12), were isolated and identified from a coral-associated fungus Aspergillus terreus. Their structures were elucidated by HRESIMS, one- and two-dimensional NMR analysis, and the absolute configuration of 2 was determined by comparison of its electronic circular dichroism (ECD) spectrum with the literature. Structurally, compound 1 featured an unusual (E)-oxime group, which occurred rarely in natural products. Compounds 1-3 were evaluated for the α-glucosidase inhibitory activity, and compound 2 showed potent inhibitory potency with IC 50 value of 104.8 ± 9.5 μM, which was lower than the positive control acarbose (IC 50  = 154.7 ± 8.1 µM). Additionally, all the isolated compounds were evaluated for the anti-inflammatory activity against NO production, and compounds 1-3, 5-7, and 10 showed significant inhibitory potency with IC 50 values ranging from 5.48 to 29.34 μM., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Matrix Metalloproteinases (MMPs) have been implicated in the pathogenesis of acute myocardial infarction (AMI). However, little is known about the association between MMP-9 and myocardial no-reflow. The aim of this study was to evaluate the role of MMP-9 in the culprit coronary artery as a predictor of no-reflow in patients with ST-elevation AMI., Methods: Ninety patients with ST-elevation AMI who underwent emergency percutaneous coronary intervention were consecutively recruited in this study. Blood samples were obtained from the extraction catheter placed distal to the culprit lesion at the beginning of percutaneous coronary intervention. No-reflow was defined as a coronary thrombolysis in myocardial infarction flow grade ≤2 after vessel reopening or thrombolysis in myocardial infarction flow 3 with a final myocardial blush grade ≤2., Results: No-reflow was observed in 25 patients (27.8%). Using multiple logistic regression analysis, local MMP-9 levels (odds ratio [OR] = 3.356; confidence interval [CI]: 1.441-5.881; P = 0.007) were found to be a significant risk factor of no-reflow together with lesion length (OR = 6.985; CI: 2.574-11.533; P = 0.009) and time to balloon (OR = 2.143; CI: 1.216-5.901; P = 0.042)., Conclusions: Elevation of MMP-9 level in the culprit coronary artery may predict no-reflow in patients with ST-elevation AMI.