Objective:To compare the efficacy and safety of continuous venetoclax combined azacitidine (VA) chemotherapy and intermedium/high-dose cytarabine (I/HDAC) consolidation in patients with acute myeloid leukemia (AML) fit for standard chemotherapy (transform from UNFIT) .Methods:Clinical data of patients who were fit for standard chemotherapy were collected among those with AML who underwent VA induction in the Department of Hematology, the Second Hospital of Hebei Medical University. The overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and incidence of adverse events were analyzed retrospectively.Results:This study enrolled 69 patients, consisting of 46 cases in the VA group and 23 cases in the I/HDAC group. We revealed the following. ① The median OS, RFS, EFS were 26.18, 24.69, 20.34 months in the VA group, and 34.14, 30.99, 28.42 months in the I/HDAC group, respectively, with no statistically significant difference (all P>0.05). Median OS of patients who underwent I/HDAC consolidation with European Leukemia Net (ELN) favorable-risk, positive measurable residual disease (MRD), wild type FLT3, or IDH1/2 mutation was significantly longer than those who received VA ( P<0.05). ②Adverse events rate of grade 3 - 4 neutropenia, grade 3 - 4 thrombocytopenia, and bacteremia were significantly lower in the VA group than in the I/HDAC group ( P<0.05) . Conclusions:I/HDAC consolidation was more likely to help get survival benefits for patients with ELN favorable-risk, positive MRD, wild type FLT3, or IDH1/2 mutation. Continuous VA chemotherapy exhibited superior safety than I/HDAC consolidation.

Objective:To evaluate the value of deep-inhaled breath-hold (DIBH)-30s scanning with total-body PET/CT under half-dose injection mode in improving the poor alignment of thoracic and upper abdominal tumors.Methods:Forty-six patients (28 males, 18 females, age (57.3±11.4) years) who underwent half-dose 18F-FDG total-body DIBH-30s PET/CT examination because of suspect or confirmed thoracic and upper abdominal tumors in Sun Yat-Sen University Cancer Center between October 2022 and February 2023 were analyzed retrospectively. SUV, standard deviation (SD) and signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in free breath (FB)-8min, FB-30s and DIBH-30s PET images were measured; SUV of lesions, metabolic tumor volume (MTV) and tumor-to-background ratio (TBR) in DIBH-30s and FB-8min images were also measured; maximum diameter of contraposition offset and offset rate in coronal, transverse and sagittal directions of lesions in DIBH-30s and FB-8min images were calculated. Five-point Likert scale was used to score the overall image quality, image noise level and diagnostic confidence of fused images. Kruskal-Wallis rank sum test, Nemenyi test or Mann-Whitney U test was used to compare the parameters of different groups. Results:Among the 46 patients, 38 successfully completed breath-holding collection, and 80 lesions were detected, including 37 in the lungs and 43 in the livers. The liver SUV max (3.40(3.15, 3.63), 3.44(3.06, 3.70)) and SD (0.36(0.32, 0.41), 0.35(0.30, 0.40)) in DIBH-30s group and FB-30s group were higher than those (SUV max: 2.73(2.45, 2.92), SD: 0.15(0.13, 0.17)) in FB-8min group ( H values: 49.79, 85.27, χ2 values: 3.26-3.65, all P<0.001). The SUV max and the SD of mediastinal blood pool in DIBH-30s group and FB-30s group were also higher ( H values: 9.31, 59.73, χ2 values: 2.13-2.75, all P<0.01), while SNR liver and SNR med in those 2 groups were lower ( H values: 87.90, 54.11, χ2 values: 3.36-5.47, all P<0.001). The image noise scores of DIBH-30s group and FB-30s group were lower than the score of FB-8min group (3(3, 3) vs 3(3, 4) vs 5(5, 5); H=93.02, χ2 values: 2.13, 2.23, all P<0.001). The overall image quality score and diagnostic confidence score of DIBH-30s group were higher than those of FB-30s group and FB-8min group ( H values: 70.13, 24.22, χ2 values: 2.11-2.48, all P<0.001). The SUV and TBR of lesions in DIBH-30s group were higher than those of FB-8min group ( Z values: from -3.82 to -2.44, all P<0.05), while the MTV, contraposition offset and offset rate were lower than those of FB-8min group ( Z values: from -6.20 to -3.18, all P<0.001). Conclusions:DIBH-30s scanning with total-body PET/CT can make the focus alignment more accurate, which is suitable for short-time collection or low drug administration activity. It has a unique value in improving the poor focus alignment of chest and upper abdomen tumors.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Amoenucles A-F (1-6), six previously undescribed nucleoside derivatives, and two known analogs (7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography, and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance (NMR), electric circular dichroism (ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α (TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.
Aspergillus/chemistry* ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Molecular Structure ; Nucleosides/isolation & purification* ; Crystallography, X-Ray ; Animals ; Humans ; Mice ; Magnetic Resonance Spectroscopy

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Concepts are the cornerstone of the development of disciplines. The concepts of TCM present that a superior concept contains more subordinate concepts. The superordinate concepts are often used to refer to different subordinate concepts, which can refer to both superior concepts themselves and non-specific subordinate concepts, that is, the characteristics of subordinate coverage and indefinite reference, which cause confusion in concept meaning, concept relationships, reasoning logic, and other problems. Nowadays, the TCM scholars pay little attention to this characteristic. Therefore, this article analyzed this characteristic, discussed its impact on the inheritance and development of TCM, and proposed that starting from the anchoring of concepts and entities to clarify the connotation of concepts, looking forward to provide new ideas for the definition of the concepts of TCM and the development of the discipline.