Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

T cell receptor ß repertoires in patients with COVID-19 reveal disease severity signatures.

Background: The immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity. Methods: In this study, we employed high-throughput T cell receptor (TCR) ß repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes. Results: We observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression. Conclusions: Our study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR ß repertoires in monitoring disease development and indicating disease severity.

Spontaneous acute epidural hematoma secondary to skull and dural metastasis of hepatocellular carcinoma: A case report.

BACKGROUND: The skull and dura are uncommon sites for the metastasis of hepatocellular carcinoma (HCC). Spontaneous acute epidural hematoma (AEDH) is also very rare. We report here a spontaneous AEDH secondary to skull and dural metastasis of HCC. This case is extremely rare. CASE SUMMARY: A 48-year-old male patient with a history of HCC developed unconsciousness spontaneously. Head computed tomography showed "a huge AEDH in the left parietal and occipital region with osteolytic destruction of the left parietal bone. Emergent operation was performed to evacuate the hematoma and resect the lesion. Pathological study revealed that the lesion was the metastases from HCC. The patient died of lung infection, anemia, and liver failure 3 wk after operation. CONCLUSION: Spontaneous AEDH caused by hepatocellular carcinoma (HCC) dural and skull metastases is extremely rare, the outcome is poor. So, early diagnosis is important. If the level of AFP does not decrease with the shrinkage of intrahepatic lesions after treatment, it is necessary to be alert to the existence of extrahepatic metastases. Since most of the patients had scalp and bone masses, physicians should pay attention to the patient's head palpation. Once a patient with the history of HCC had sudden neurological dysfunction, the possibility of spontaneous AEDH caused by the skull and dura mater metastases should be considered. Since hemorrhage is common in the skull HCC metastases, for patients with spontaneous AEDH accompanied by skull osteolytic lesions, it is also necessary to be alert to the possibility of HCC. For AEDH secondary to HCC metastases, early diagnosis and timely treatment are critical to improve the patients' outcomes.

Desiccation and cold storage of Galleria mellonella cadavers and effects on in vivo production of Steinernema carpocapsae.

BACKGROUND: Direct application of insect cadavers infected with entomopathogenic nematodes (EPN) can successfully control target pest insects. Little is known about the effects of environmental factors (desiccation and temperature) on the production process for infective juveniles (IJ) in insects. RESULTS: We examined the effects of desiccation time and cold storage (6.7 °C) on IJ production of the nematode Steinernema carpocapsae in Galleria mellonella cadavers at 30.8 and 57% humidity. Under desiccation, the IJ yield in cadavers increased gradually and reached a maximum on day 5. IJ yield gradually declined from day 6 onwards and was almost zero by day 15. In general, cold storage at 6.7 °C caused negative effects on IJ production in desiccated cadavers. Approximately 56 h post infection was the time at which nematodes were most sensitive to low temperatures during development in cadavers. Five-day desiccated cadavers generated higher mortality and more rapid death of Galleria mellonella larvae than using newly (day 0) desiccated cadavers. CONCLUSION: This study describe methods of optimizing rearing techniques such as desiccation and cold storage to promote the mass production and application of EPN- infected host cadavers for the field control of insect pests.