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.

Influences of Propofol, Ciprofol and Remimazolam on Dreaming During Anesthesia for Gastrointestinal Endoscopy: A Randomized Double-Blind Parallel-Design Trial.

Purpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy. Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected. Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups. Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.

Intermittent melena and refractory anemia due to jejunal cavernous lymphangioma: A case report.

BACKGROUND: Lymphangiomas in the gastrointestinal tract are extremely rare in adults. As a benign lesion, small intestine lymphangiomas often remain asymptomatic and pose challenges for definitive diagnosis. However, lymphangiomas can give rise to complications such as abdominal pain, bleeding, volvulus, and intussusception. Here, we report a case of jejunal cavernous lymphangioma that presented with intermittent melena and refractory anemia in a male adult. CASE SUMMARY: A 66-year-old man presented with intermittent melena, fatigue and refractory anemia nine months prior. Esophagogastroduodenoscopy and colonoscopy were performed many times and revealed no apparent bleeding. Conservative management, including transfusion, hemostasis, gastric acid secretion inhibition and symptomatic treatment, was performed, but the lesions tended to recur shortly after surgery. Ultimately, the patient underwent capsule endoscopy, which revealed a more than 10 cm lesion accompanied by active bleeding. After single-balloon enteroscopy and biopsy, a diagnosis of jejunal cavernous lymphangioma was confirmed, and the patient underwent surgical resection. No complications or recurrences were observed postoperatively. CONCLUSION: Jejunal cavernous lymphangioma should be considered a cause of obscure gastrointestinal bleeding. Capsule endoscopy and single-balloon enteroscopy can facilitate diagnosis. Surgical resection is an effective management method.

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).

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.

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.

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.

Exercise-induced Musclin determines the fate of fibro-adipogenic progenitors to control muscle homeostasis.

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.

Diverse ansamycin derivatives from the marine-derived Streptomyces sp. ZYX-F-97 and their antibacterial activities.

Four new ansamycin derivatives, named 1,19-epithio-geldanamycin A (1), 17-demethoxylherbimycin H (2), herbimycin M (3), and seco-geldanamycin B (4), together with eight known ansamycin analogues (5-12) were isolated from the solid fermentation of marine-derived actinomycete Streptomyces sp. ZYX-F-97. The structures of new compounds were elucidated by extensive spectroscopic analysis as well as nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) calculations. All the compounds were assayed for their antibacterial activity. Among them, compounds 4, 8, and 12 exhibited remarkable inhibition against Listeria monocytogenes with minimum inhibitory concentrations (MIC) values ranging from 8 µg·mL-1 to 64 µg·mL-1, and displayed moderate inhibition against methicillin-resistant Staphylococcus aureus (MRSA) with MIC value of 64 µg·mL-1. Compounds 4, 8, 9, and 12 showed moderate inhibition activities against both Staphylococcus aureus and Bacillus subtilis with MIC values ranging from 32 µg·mL-1 to 128 µg·mL-1.

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.

Lanostane triterpenoids from the fruiting bodies of Ganoderma amboinense.

Lanostane-type triterpenoids are the main characteristic constituents in Ganoderma mushrooms. Phytochemical analysis on the ethanol extract of the fruiting bodies of Ganoderma amboinense led to isolation and identification of twelve previously undescribed lanostane triterpenoids (1-12). Their chemical structures were determined by HR-ESI-MS, IR, and NMR spectroscopic analysis, NMR calculation, as well as X-ray crystallography. All isolates were evaluated for the α-glucosidase inhibitory and anti-inflammatory activities. Compounds 1, 5, 6, and 11 showed significant α-glucosidase inhibitory activity with IC50 values ranging from 33.5 µM to 96.0 µM. Moreover, compound 12 showed anti-inflammatory activity with IC50 value of 21.7 ± 2.1 µM.

[Multicellular coupling fermentation for 3'-sialyllactose conversion using N-acetyl-glucosamine and lactose].

Sialyllactose is one of the most abundant sialylated oligosaccharides in human milk oligosaccharides (HMOs), which plays an important role in the healthy development of infants and young children. However, its efficient and cheap production technology is still lacking presently. This study developed a two-step process employing multiple-strains for the production of sialyllactose. In the first step, two engineered strains, E. coli JM109(DE3)/ pET28a-BT0453 and JM109(DE3)/pET28a-nanA, were constructed to synthesize the intermediate N-acetylneuraminic acid. When the ratio of the biomass of the two engineered strains was 1:1 and the reaction time was 32 hours, the maximum yield of N-acetylneuraminic acid was 20.4 g/L. In the second step, E. coli JM109(DE3)/ pET28a-neuA, JM109(DE3)/ pET28a-nst and Baker's yeast were added to the above fermentation broth to synthesize 3'-sialyllactose (3'-SL). Using optimal conditions including 200 mmol/L N-acetyl-glucosamine and lactose, 150 g/L Baker's yeast, 20 mmol/L Mg2+, the maximum yield of 3'-SL in the fermentation broth reached 55.04 g/L after 24 hours of fermentation and the conversion rate of the substrate N-acetyl-glucosamine was 43.47%. This research provides an alternative technical route for economical production of 3'-SL.

Diverse indole-diterpenoids with protein tyrosine phosphatase 1B inhibitory activities from the marine coral-derived fungus Aspergillus sp. ZF-104.

Eight previously undescribed indole-diterpenoids named penerpenes O-V (1-8), together with seven known analogues (9-14), were isolated from the marine soft coral-derived fungus Aspergillus sp. ZF-104. Their structures including the absolute configurations of these compounds were assigned on the basis of spectroscopic data and ECD analysis along with quantum ECD and NMR calculations. Compounds 4 and 5 bear rare indolin-2-one units in their structures and 6 bears a reconstructed novel skeleton in which the indole ring and the terpenoid substructure are cleaved before they are reconnected through the nitrogen atom. Compounds 1, 2, 7, and 10 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory activities comparable to that of the positive control NaVO3.

Lanostane triterpenoids with anti-proliferative and PTP1B/α-glucosidase inhibitory activities from the fruiting bodies of Ganoderma calidophilum.

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H-S (1-12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 µM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC50 values of 30.2 ± 0.13 µM and 120.6 ± 0.14 µM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations.

[Application of hairpin shaped incision combined with cover-lifting flap in plastic surgery of huge fat pad on nape and back].

Objective: To explore the effectiveness of hairpin shaped incision combined with cover-lifting flap in plastic surgery of huge fat pad on nape and back. Methods: Between March 2019 and March 2023, 10 patients with huge fat pad on the nape and back were treated. There was 1 male and 9 females with an average age of 52 years (range, 39-57 years). All patients had soft tissue bulge on the nape and back. Preoperative MRI showed the subcutaneous fat thickening. The length of the longitudinal axis of the fat pad ranged from 10.0 to 25.0 cm (mean, 14.1 cm), the length of the transverse axis ranged from 6.0 to 15.0 cm (mean, 10.8 cm); the thickness of the fat pad ranged from 2.5 to 5.1 cm (mean, 3.9 cm). Under general anesthesia, the patient was placed in a prone position and a hairpin shaped incision was made. The flap was lifted to remove the fat pad according to the marked area. The dressing was changed every 2 days after operation. Results: The operation time was 35-110 minutes (mean, 72 minutes). The intraoperative blood loss was 35-80 mL (mean, 49.5 mL). The drainage tube was removed at 2-5 days after operation (mean, 3.4 days). All incisions healed by first intention without incision dehiscence, infection, subcutaneous bruising, hematoma, or other related complications. All patients were followed up 2-24 months (mean, 12 months). All patients had a good shape of the nape and back and no noticeable scar on the incision. According to the Vancouver Scar Scale evaluation criteria, the incision scar score was 3-5 (mean, 3.7) at 2 months after operation. Patients had good neck movement with no recurrence. Conclusion: For the huge fat pad on the nape and back, the plastic surgery using hairpin shaped incision and cover-lifting flap has the advantages of fully exposing the fat pad, concealed incision, simple operation, and natural shape of the nape and back after operation.

Asperphenalenones Isolated from the Biocontrol Agent Clonostachys rosea and Their Antimicrobial Activities.

Clonostachys rosea is a fungus widely distributed on Earth and has a high capacity to adapt to complex environments in soil, plants, or sea. It is an endophyte that can be used as a potential biocontrol agent to protect plants from pathogenic fungi, nematodes, and insects. However, the spectrum of secondary metabolites produced by C. rosea has only scarcely been studied. In the present study, eight new phenalenones, asperphenalenones F-M (1-8), together with two known derivatives, asperphenalenones E and B (9 and 10), were isolated from the axenic rice culture of this fungus. The structures of the new compounds were elucidated by nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism, and gas chromatography-mass spectrometry analyses. Asperphenalenones J-M (5-8) are unusual phenalenone adducts that are conjugated to diterpenoid glycosides. Asperphenalenones F and H showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus, with minimal inhibitory concentrations of 12.5 and 25 µM, respectively. Asperphenalenone B exhibited low antiviral activity against the human immunodeficiency virus replication. Furthermore, asperphenalenones F and H exhibited low cytotoxicity against Jurkat cells, while all other compounds were devoid of cytotoxicity.

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).

[Effectiveness of fascial tissue flaps and skin flaps with layered sutures for repair of wounds after excision of sacrococcygeal pilonidal sinus].

Objective: To investigate the feasibility and effectiveness of fascial tissue flaps and skin flaps with layered sutures for repairing wounds after excision of sacrococcygeal pilonidal sinus. Methods: Between March 2019 and August 2022, 9 patients with sacrococcygeal pilonidal sinus were admitted, including 7 males and 2 females with an average age of 29.4 years (range, 17-53 years). The disease duration ranged from 1 to 36 months, with a median of 6 months. There were 7 cases with obesity and dense hair, 3 cases with infection, and 2 cases with positive bacterial culture of sinus secretion. The wound area after excision ranged from 3 cm×3 cm to 8 cm×4 cm, with a depth of 3-5 cm, reaching the perianal or caudal bone; there were 2 cases with perianal abscess formation and 1 case with caudal bone inflammatory edema. Enlarged resection was performed during operation, and the fascial tissue flap and skin flap were designed and excised at both left and right sides of the buttock, ranging from 3.0 cm×1.5 cm to 8.0 cm×2.0 cm. A cross drainage tube was placed at the bottom of the wound, and the fascial tissue flap and skin flap were advanced and sutured in three layers, namely, 8-string sutures in the fascial layer, barbed wire reduction sutures in the dermis, and interrupted skin sutures. Results: All 9 patients were followed up 3-36 months, with an average of 12 months. All incisions healed by first intention, and no complication such as incisional dehiscence or infection in the operative area occurred. There was no recurrence of sinus tracts, the shape of gluteal sulcus was satisfactory, both sides of buttocks were symmetrical, local incision scar was concealed, and the shape disruption was minimal. Conclusion: Fascial tissue flaps and skin flaps with layered sutures for repairing wounds after excision of sacrococcygeal pilonidal sinus can effectively fill the cavity and reduce the incidence of poor incision healing, with the advantages of small trauma and simple operation.

Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K+CD8+ T cells in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell-dominated destruction of exocrine glands. Currently, CD8+ T cells are thought to be involved in the pathogenesis of pSS. However, the single-cell immune profiling of pSS and molecular signatures of pathogenic CD8+ T cells have not been well elucidated. Our multiomics investigation showed that both T cells and B cells, especially CD8+ T cells, were undergoing significant clonal expansion in pSS patients. TCR clonality analysis revealed that peripheral blood granzyme K+ (GZMK+) CXCR6+CD8+ T cells had higher a proportion of clones shared with CD69+CD103-CD8+ tissue-resident memory T (Trm) cells in labial glands in pSS. CD69+CD103-CD8+ Trm cells featured by high expression of GZMK were more active and cytotoxic in pSS compared with their CD103+ counterparts. Peripheral blood GZMK+CXCR6+CD8+ T cells with higher CD122 expression were increased and harbored a gene signature similar to Trm cells in pSS. Consistently, IL-15 was significantly elevated in pSS plasma and showed the capacity to promote differentiation of CD8+ T cells into GZMK+CXCR6+CD8+ T cells in a STAT5-dependent manner. In summary, we depicted the immune profile of pSS and further conducted comprehensive bioinformatics analysis and in vitro experimental investigations to characterize the pathogenic role and differentiation trajectory of CD8+ Trm cells in pSS.

Two new alkaloids from the endophytic fungus Schizophyllum sp. HM230 isolated from Vincetoxicum mongolicum Maxim.

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M (1) and N (2), along with three known ones (3-5). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1-4 showed middle cytotoxicity against MCF-7 cells with IC50 values range of 68.1 ∼ 87.32 µM. Compounds 1-5 displayed obvious antioxidant activity with the IC50 values range of 0.86 ∼ 5.78 mg/mL.