Bone marrow CD8+ Trm cells induced by IL-15 and CD16+ monocytes contribute to HSPC destruction in human severe aplastic anemia.

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.

Phytohabitans maris sp. nov., isolated from marine sediment.

A novel actinobacterium, strain ZYX-F-186T, was isolated from marine sediment sampled on Yongxing Island, Hainan Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain ZYX-F-186T belongs to the genus Phytohabitans, with high similarity to Phytohabitans kaempferiae KK1-3T (98.3 %), Phytohabitans rumicis K11-0047T (98.1 %), Phytohabitans flavus K09-0627T (98.1 %), Phytohabitans houttuyneae K11-0057T (97.9 %), Phytohabitans suffuscus K07-0523T (97.7 %), and Phytohabitans aurantiacus RD004123T (97.7 %). Phylogenetic analysis of 16S rRNA gene sequences showed that the strain formed a single subclade in the genus Phytohabitans. The novel isolate contained meso-diaminopimelic acid, d-glutamic acid, glycine, d-alanine, and l-lysine in the cell wall. The whole-cell sugars were xylose, arabinose, ribose, and rhamnose. The predominant menaquinones were MK-9(H8), MK-9(H6), and MK-9(H4). The characteristic phospholipids were phosphatidylethanolamine, phosphatidylinositol, phosphatidylmethylethanolamine, phosphatidylglycerol, and an unknown phospholipid. The major fatty acids (>5 %) were iso-C16 : 0, anteiso-C17 : 0, and iso-C18 : 0. Genome sequencing showed a DNA G+C content of 71.9 mol%. Low average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values demonstrated that strain ZYX-F-186T could be readily distinguished from its closely related species. Based on its phylogenetic, chemotaxonomic, and physiological characteristics, strain ZYX-F-186T represents a novel species of the genus Phytohabitans, for which the name Phytohabitans maris sp. nov. is proposed. The type strain is ZYX-F-186T (=CGMCC 4.8025T=CCTCC AA 2023025T=JCM 36507T).

Semisynthesis and antitumor activity of endertiin B and related triterpenoids from Ganoderma lucidum.

Ganoderma lucidum, a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo. Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 µM and 12.12 ± 0.95 µM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.

Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143.

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 µM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 µM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Diaporchalasins A-E, New Cytochalasins from the Endophytic Fungus Diaporthe sp. BMX12 Isolated from Aquilaria sinensis.

Five new cytochalasins, diaporchalasins A-E (1-5), together with 14 known congeners (6-19) were isolated from the endophytic fungus Diaporthe sp. BMX12, which was isolated from the branches of Aquilaria sinensis. The structures of the new compounds were elucidated by extensive spectroscopic analyses including high-resolution electron spray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). Their absolute configurations were assigned by theoretical electronic circular dichroism (ECD) calculations. Compounds 11 and 12 featuring a keto carbonyl at C-21 displayed cytotoxicity toward K562, BEL-7402, SGC-7901, A549, and HeLa cell lines with IC50 values ranging from 4.4 to 47.4 µM.

Chemical constituents of the marine-derived fungus Acremonium sp. AN-13.

Two new compounds named 3(S)-hydroxy-1-(2,4,5-trihydroxy-3,6- dimethylphenyl)-hex-4E-en-1-one (1) and acremonilactone (2), together with nine known compounds (3-11), were isolated from the fermentation broth of Acremonium sp. associated with marine sediments collected from South China Sea. NMR and HRESIMS spectroscopic analysis elucidated the structure of two new compounds. Compound 2 had characteristic rotary gate shape skeleton with a six-membered lactone. Compounds 1 and 9 showed DPPH radical scavenging activity with inhibition rates of 96.50 and 85.95% at the concentration of 0.5 mg/ml, respectively. Moreover, compounds 4, 6 and 11 showed definite antibacterial activity against Staphylococcus aureus ATCC 6538.

Actinoplanes maris sp. nov., isolated from marine sediment.

A novel actinobacterium strain (M4I6T) was isolated from marine sediment collected in Megas Gialos, Syros, Greece. On the basis of 16S rRNA gene sequence analysis, strain M4I6T was indicated as belonging to the genus Actinoplanes, with high similarity to 'Actinoplanes solisilvae' LAM7112T (97.9 %), Actinoplanes ferrugineus IFO 15555T (97.6 %), Actinoplanes cibodasensis LIPI11-2-Ac042T (97.2 %) and Actinoplanes bogorensis LIPI11-2-Ac043T (97.2 %). Phylogenetic analysis of the 16S rRNA gene sequence of strain M4I6T showed that the strain formed a stable subclade with 'A. solisilvae' LAM7112T. The cell wall of the novel isolate contained meso-diaminopimelic acid and the whole-cell sugars were xylose, glucose and ribose. The predominant menaquinones were MK-9(H4), MK-9(H2) and MK-9(H8). The phospholipid profile comprised phosphatidylethanolamine, phosphatidylinositol, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol mannosides and an unknown phospholipid. The major fatty acids (>5 %) were anteiso-C16 : 0, iso-C17 : 0, 10-methyl-C16 : 0, C15 : 0, iso-C16 : 0 and C17 : 0. Genome sequencing showed a DNA G+C content of 70.9 mol%. However, the low average nucleotide identity value, digital DNA-DNA hybridization and average amino acid identity values demonstrated that strain M4I6T could be readily distinguished from its closest related species. Based on data from this polyphasic study, strain M4I6T represents a novel species of the genus Actinoplanes, for which the name Actinoplanes maris sp. nov. is proposed. The type strain is M4I6T (=DSM 101017T=CGMCC 4.7854T).

Hexahydroazulene-2(1H)-one Sesquiterpenoids with Bridged Cyclobutane, Oxetane, and Tetrahydrofuran Rings from the Stems of Daphne papyracea with α-Glycosidase Inhibitory Activity.

Chemical investigation of an alcoholic extract from the stem of Daphne papyracea ("Xuehuagou") led to the isolation of the tetracyclic sesquiterpenoid daphnepapytone A (1), containing a unique caged skeleton with a cyclobutane ring having three tetrasubstituted chirality centers. Also isolated were new guaiane sesquiterpenoids, namely, daphnepapytones B-H (2-8), and one 1,5-diphenylpentanone 2-hydroxy-5-oxo-daphneone (9), together with 26 known compounds. The cyclic metabolites share a 5-isoprenyl-hexahydroazulene-2(1H)-one skeleton with different substitution patterns and a bridged cyclobutane, oxetane, or tetrahydrofuran ring. The planar structures and relative configuration of the new compounds were elucidated on the basis of spectroscopic analysis aided by DFT 13C NMR calculations. The absolute configurations of 1-7 were determined by X-ray single-crystal diffraction or TDDFT-ECD calculations. Daphnepapytones A and C (1 and 3), 2-hydroxy-5-oxodaphneone (9), daphnenone (10), daphneone (11), and 3-methyldaphneolone (12) showed α-glycosidase inhibitory activity, with IC50 values of 159.0, 102.3, 139.3, 43.3, 145.0, and 126.1 µM, respectively.

Phenethoxy Derivatives with Anti-inflammatory Activities from the Betelnut Endophytic Trichoderma asperellum G10.

Eight new phenethoxy derivatives, trichoasperellins A-H (1-8), were isolated from the endophytic fungus Trichoderma asperellum G10 isolated from the medicinal plant Areca catechu L. The structures of these compounds were elucidated from spectroscopic data, J-based configurational analysis, and Mosher's methods. Compounds 1-4 and 6-8 bear one or two multioxidized C7 moieties with the same carbon skeleton. The carbon skeletons of compounds 6-8 are new, all containing three moieties connected via two acetal carbons similar to those of disaccharide glycosides. Compound 4 inhibited nitric oxide production with an IC50 value of 48.3 µM, comparable to that of the positive control indomethacin (IC50, 42.3 µM).

Antidiabetic lanostane triterpenoids from the fruiting bodies of Ganoderma weberianum.

Eight previously undescribed lanostane triterpenoids, ganodeweberiols A âˆ¼ H (1-8), together with eighteen known compounds (9-26), were isolated from the fruiting bodies of Ganoderma weberianum. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic analysis, as well as NMR chemical shifts and electronic circular dichroism (ECD) calculations. Compounds 2, 7, 12, and 14 showed significant α-glucosidase inhibitory activity with IC50 values ranging from 35.3 µM âˆ¼ 223.4 µM compared to the positive control acarbose (IC50, 304.6 µM). Kinetic study indicated that the most potent compound 12 was a mixed type inhibitor for α-glucosidase. Molecular docking simulation revealed the interactions of 12 with α-glucosidase. Additionally, Compounds 3 and 6 inhibited glucagon-induced hepatic glucose production in HepG2 cells with EC50 values of 42.0 and 85.9 µM, respectively. Further study revealed that compounds 3 and 6 inhibited hepatic glucose production by suppression glucagon-induced cAMP accumulation. Moreover, compounds 3 and 26 were active against HeLa cell line with IC50 values of 17.0 and 6.8 µM, respectively.

Histologic and biomechanical evaluation of the thoracolumbar fascia graft for massive rotator cuff tears in a rat model.

BACKGROUND: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing. METHODS: A total of 88 rats were used in this study. Eight rats were killed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the TLF augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3 × 5 mm defect of the supraspinatus was created. The TLF was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8, and 16 weeks postoperatively. RESULTS: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 ± 0.71 vs. 24.40 ± 0.89, P = .025) and 16 weeks (24.60 ± 0.55 vs. 26.40 ± 0.55, P ≤ .001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8, and 16 weeks (24.78% ± 2.76% vs. 20.67% ± 2.11% at 4 weeks, P = .046; 25.46% ± 1.77% vs. 21.49% ± 2.33% at 8 weeks, P = .026; 34.77% ± 2.25% vs. 30.01% ± 3.17% at 16 weeks, P = .040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 ± 2.49 N vs. 23.10 ± 3.47 N, P = .022). CONCLUSIONS: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for superior capsule reconstruction (SCR).

Hydraulic conductivity of novel geosynthetic clay liner to bauxite liquor from China: Modified fluid loss test evaluation.

A modified sodium bentonite geosynthetic clay liner (GCL) designed for acid-and-alkaline resistance was evaluated for its potential application in the containment of bauxite residue leachate. A modified fluid loss test was employed to quickly evaluate the hydraulic conductivity (k) of the GCL using distilled water, tap water, and four bauxite liquors (BLs, leachate from bauxite residue reservoirs). The effects of swelling capacity of bentonite, prehydration, hydraulic gradient (i), ionic strength (I), and relative abundance of monovalent and multivalent cations (RMD) on the hydraulic conductivity of the GCL were analyzed. The results indicated that the BLs significantly decreased free swell index of the bentonite. As compared to increasing i, prehydration obviously enhanced hydraulic performance of the GCL. The four BLs increased k of the GCL by a factor of 4-12 relative to the tap water permeation condition, and the resultant k exceeded upper limit of 5.0 × 10-11 m/s for GCLs. The increase in k was attributed to compression in diffuse double layer of the bentonite and dissolution in clay minerals in ion-rich and hyperalkaline BLs, manifesting that further modification on the GCL is needed. The I was found a better indicator than the RMD on correlation with chemical compatibility of the GCL.

Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in human tumors.

BACKGROUND: In recent years, there have been many studies on the relationship between DLGAP5 and different types of cancers, yet there is no pan-cancer analysis of DLGAP5. Therefore, this study aims to analyze the roles of DLGAP5 in human tumors. METHODS: Firstly, we evaluated the expression level of DLGAP5 in 33 types of tumors throughout the datasets of TCGA (Cancer Genome Atlas) and GEO (Gene Expression Synthesis). Secondly, we used the GEPIA2 and Kaplan-Meier plotter to conduct Survival prognosis analysis. Additionally, cBioPortal web was utilized to analyze the genetic alteration of DLGAP5, after which we selected hepatocellular carcinoma (HCC) cell lines to define the function of DLGAP5. Last but not least, we performed immune infiltration analysis and DLGAP5-related gene enrichment analysis. RESULTS: DLGAP5 is highly expressed in most type of cancers, and there is a significant correlation between the expression of DLGAP5 and the prognosis of cancer patients. We have observed that DLGAP5 promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cell lines. We also found that DLGAP5 expression was related with the CD8+ T-cell infiltration status in kidney renal clear cell carcinoma, uveal melanoma, and thymoma, and cancer-associated fibroblast infiltration was observed in breast invasive carcinoma, kidney renal papillary cell carcinoma and testicular germ cell tumors. In addition, enrichment analysis revealed that cell cycle- and oocyte meiosis-associated functions were involved in the functional mechanism of DLGAP5. CONCLUSIONS: Taken together, our unpresented pan-cancer analysis of DLGAP5 provides a relatively integrative understanding of the oncogenic role of DLGAP5 in various tumors. DLGAP5 may prompt HCC cellular proliferation, invasion and metastasis. All of these provides solid basement and will promote more advanced understanding the role of DLGAP5 in tumorigenesis and development from the perspective of clinical tumor samples and cells.

Triterpenoids and meroterpenoids with α-glucosidase inhibitory activities from the fruiting bodies of Ganoderma australe.

Macrofungi Ganoderma is a valuable medicinal fungus resource for human health and longevity in China. In this study, ten undescribed compounds including seven lostane-type triterpenoids, ganodaustralic acids A âˆ¼ G (1-7), one pair of meroterpenoid enantiomers, (-)-6'-O-ethyllingzhiol (8) and (+)-6'-O-ethyllingzhiol (9), and one polyhydroxylated sterol, 3-O-acetyl-fomentarol C (10), together with eight known compounds (11-18), were isolated from the fruiting bodies of Ganoderma australe. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and electronic circular dichroism (ECD) calculations. Compounds 4, 8, 9, and 12 showed significant α-glucosidase inhibitory activities with IC50 values in the range of 4.1-11.7 µM, which were superior to that of positive control acarbose (213 µM). Only compound 7 exhibited weak cytotoxicity against SGC-7901 cells.

Cytotoxic Indole-Diterpenoids from the Marine-Derived Fungus Penicillium sp. KFD28.

Four new indole-diterpenoids, named penerpenes K-N (1-4), along with twelve known ones (5-16), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds (4, 9, and 15) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 µM. Moreover, six compounds (5, 7, 10, 12, 14, and 15) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

Asperpenes D and E from the fungus Aspergillus sp. SCS-KFD66 isolated from a bivalve mollusk, Sanguinolaria chinensis.

Two new compounds named asperpenes D (1) and E (2) were isolated from the marine-derived fungus Aspergillus sp. SCS-KFD66. Their structures were determined on the basis of spectroscopic methods. Compound 2 represents the first natural product bearing a 2-substituted-5-oxo-4-phenyl-2,5-dihydrofuran-3-carboxylic acid skeleton. All the compounds were tested for enzyme inhibitory activity against AChE and α-glucosidase and DPPH radical scavenging activity, respectively. [Formula: see text].

Two new indole-diterpenoids from the marine-derived fungus Penicillium sp. KFD28.

Two new compounds named epipaxilline (1) and penerpene J (2) were isolated from the marine-derived fungus Penicillium sp. KFD28. Their structures including absolute configurations were determined on the basis of spectroscopic methods and ECD analysis. Compounds 1 and 2 showed inhibitory activities against PTP1B with IC50 values of 31.5 and 9.5 µM, respectively, and compound 2 also showed inhibitory activities against TCPTP with IC50 value of 14.7 µM.

[Study on chemical constituents from fruiting bodies of Ganoderma calidophilum].

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11ß-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC_(50) values of 26.55, 11.35, 23.23, 18.66 µmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC_(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 µmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC_(50) value of 42.50 µmol·L~(-1).

Polyketides with quorum sensing inhibitory activity from the marine-derived fungus Aspergillus sp. ZF-79.

Seven compounds were isolated from a marine-derived fungus Aspergillus sp. ZF-79, including three new polyketides (1-3), named asperochrins D-F, along with four known compounds 4-7. Their structures were determined on the basis of spectroscopic methods. All the compounds were tested for quorum sensing inhibitory (QSI) activity. Compounds 1, 3, 4, 5, and 6 exhibited QSI activity against Chromobacterium violaceum CV026 with MIC values of 50, 100, 50, 50, and 6.25 µM, respectively.

Napthrene Compounds from Mycelial Fermentation Products of Marasmius berteroi.

The metabolites of the genus Marasmius are diverse, showing good research prospects for finding new bioactive molecules. In order to explore the active metabolites of the fungi Marasmius berteroi, the deep chemical investigation on the bioactive compounds from its cultures was undertaken, which led to the isolation of three new naphthalene compounds dipolynaphthalenes A-B (1,2) and naphthone C (3), as well as 12 known compounds (4-15). Compounds 1, 2, and 4 are dimeric naphthalene compounds. Their structures were elucidated by MS, 1D and 2D NMR spectroscopic data, as well as ECD calculations. Compounds 2-4 and 7 exhibited acetylcholinesterase (AChE) inhibitory activities at the concentration of 50 µg/mL with inhibition ratios of 42.74%, 44.63%, 39.50% and 51.49%, respectively. Compounds 5 and 7,8 showed weak inhibitory activities towards two tumor cell lines, with IC50 of 0.10, 0.076 and 0.058 mM (K562) and 0.13, 0.18, and 0.15 mM (SGC-7901), respectively.