Regulatory mucosa-associated invariant T cells controlled by ß1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression.

BACKGROUND AND AIMS: The innate-like mucosa-associated invariant T (MAIT) cells are enriched in human liver and have been linked to human HCC. However, their contributions to the progression of HCC are controversial due to the heterogeneity of MAIT cells, and new MAIT cell subsets remain to be explored. APPROACH AND RESULTS: Combining single cell RNA sequencing (scRNA-seq) and flow cytometry analysis, we performed phenotypic and functional studies and found that FOXP3 + CXCR3 + MAIT cells in HCC patients were regulatory MAIT cells (MAITregs) with high immunosuppressive potential. These MAITregs were induced under Treg-inducing condition and predominantly from FOXP3 - CXCR3 + MAIT cells, which displayed mild Treg-related features and represented a pre-MAITreg reservoir. In addition, the induction and function of MAITregs were promoted by ß1 adrenergic receptor signaling in pre-MAITregs and MAITregs, respectively. In HCC patients, high proportion of the intratumoral MAITregs inhibited antitumor immune responses and was associated with poor clinical outcomes. CONCLUSIONS: Together, we reveal an immunosuppressive subset of MAIT cells in HCC patients that contributes to HCC progression, and propose a control through neuroimmune crosstalk.

Immunosuppressed Patients with Clinically Diagnosed Invasive Fungal Infections: The Fungal Species Distribution, Antifungal Sensitivity and Associated Risk Factors in a Tertiary Hospital of Anhui Province.

OBJECTIVE: Since the nosocomial fungal infections increasingly emerge, we extensively investigated the fungal species stratification and antifungal sensitivity profiles, clinical characteristics and associated risk factors of immunosuppressed patients with clinically diagnosed invasive fungal infections (IFIs) in a tertiary hospital of Anhui province. METHODS: In total, 112 subjects with immunosuppressive state were enrolled from a comprehensive tertiary hospital in Central China between July 2019 and December 2021. Eight-one fungal isolates were clinically recovered by fungus-culturing approaches. The identifications were conducted through a mass spectrometry detecting platform. The susceptibilities to antifungals were tested using the broth micro-dilution method, and the possible antifungal azole-resistance mechanism in specific Candida species was availably explored by sequencing. Patient medical profiles were accessed via the digitized retrieval system of hospital, from which clinical outcomes and multiple risk factors for immunosuppressed patients with clinically diagnosed IFIs were explicitly documented for evaluation. RESULTS: Candida species predominated in clinically diagnosed IFIs of immunosuppressed patients (accounting for 88.88%), followed by Trichosporon and Aspergillus species (6.17% and 4.94%, respectively). The source types of specimen were primarily comprised of urine (41.98%), respiratory samples (33.33%) and peripheral blood (9.88%). Frequently isolated Candida and Trichosporon species exhibited a high level of in vitro sensitivity for amphotericin B and 5-fluorocytosine, whereas a substantial portion of Candida species including C. glabrata, C. parapsilosis complex and C. tropicalis, and Trichosporon species showed lowered sensitivity patterns toward itraconazole, fluconazole and voriconazole at different levels. Specifically, gene mutations of ERG11 were identified in azole-resistant C. tropicalis. Distinct risk factors were analyzed to be highly associated with the clinically diagnosed IFI incidence, mainly including hospitalization duration, surgical procedures, immunosuppressive treatments, underlying diseases and other conditions. CONCLUSION: Candida, Trichosporon and Aspergillus species were the top three pathogenic fungal agents causing clinically diagnosed IFIs in immunosuppressed patients. The attenuated sensitivity to azoles in Candida and Trichosporon species needs close surveillance, and ERG11 polymorphism might contribute to azole resistance in specific Candida species. Multiple featured risk factors for immunosuppressed patients developing clinically diagnosed IFIs require further consideration during clinical practice.

Identification of Cortex Eucommiae from different producing areas by FTIR microspectroscopy.

In this paper, FTIR microspectroscopy was used to compare Cortex Eucommiae from Anhui Province (A), Henan Province (B) and Sichuan Province (C) of China. High-resolution spectra were obtained with good reproducibility. From IR spectra, some obvious differences in band frequency could be observed among Cortex Eucommiae A-C. Curve fitting result indicated that polysaccharides' structures and contents were different among Cortex Eucommiae A-C. To distinguish Cortex Eucommiae from different producing areas, the A1245/A1328 ratio might be an exceptionally practical factor. Additionally, FTIR microspectroscopy could identify Cortex Eucommiae A-C with 89.5% accuracy in combination with hierarchical cluster analysis. The results suggest FTIR microspectroscopy is very easy and efficient for distinguishing Cortex Eucommiae from different areas, and also indicate FTIR microspectroscopy may be practical for TCM research.

FTIR spectroscopic comparison of serum from lung cancer patients and healthy persons.

The incidence and mortality of lung cancer remains so high that it is very urgent to develop an effective method for early detection of lung cancer. Serum can reflect physiological and pathological changes of human body, so FTIR spectroscopy was used to compare lung cancer patients' and healthy persons' serum in this study. The A1080/A1170 ratio might be potentially useful for distinguishing lung cancer patients' serum from healthy persons' serum. Moreover, the result of curve fitting indicated that the ratios of α-helix/antiparallel ß-sheet were lower for lung cancer patients' serum than those for healthy persons' serum. These results indicated that IR spectra of serum might be potentially useful for detecting lung cancer.

Distinction of leukemia patients' and healthy persons' serum using FTIR spectroscopy.

In this paper, FTIR spectroscopy was applied to compare the serum from leukemia patients with the serum from healthy persons. IR spectra of leukemia patients' serum were similar with IR spectra of healthy persons' serum, and they were all made up of proteins, lipids and nucleic acids, etc. In order to identify leukemia patients' serum and healthy persons' serum, the H1075/H1542, H1045/H1467, H2959/H2931 ratios were measured. The H2959/H2931 ratio had the highest significant difference among these ratios and might be a useful factor for identifying leukemia patients' serum and healthy persons' serum. Furthermore, from curve fitting, the RNA/DNA (A1115/A1028) ratios were observed to be lower in leukemia patients' serum than those in healthy persons' serum. The results indicated FTIR spectroscopic study of serum might be a useful tool in the field of leukemia research and diagnosis.

Comparison of serum from gastric cancer patients and from healthy persons using FTIR spectroscopy.

Since serum can reflect human beings' physiological and pathological conditions, FTIR spectroscopy was used to compare gastric cancer patients' serum with healthy persons' serum in this study. The H2959/H2931, H1646/H1550, H1314/H1243, H1453/H1400 and H1080/H1550 ratios were calculated, among these ratios, the H2959/H2931 ratio might be a standard for distinguishing gastric cancer patients from healthy persons. Then curve fitting was processed using Gaussian curves in the 1140-1000 cm(-1) region, and the result showed that the RNA/DNA ratios of gastric cancer patients' serum were obviously lower than those of healthy persons' serum. The results suggest that FTIR spectroscopy may be a potentially useful tool for diagnosis of gastric cancer.

Distinction of broken cellular wall Ganoderma lucidum spores and G. lucidum spores using FTIR microspectroscopy.

In this paper, FTIR microspectroscopy was used to identify broken cellular wall Ganoderma lucidum spores and G. lucidum spores. For IR spectra, broken cellular wall G. lucidum spores and G. lucidum spores were mainly different in the regions of 3000-2800, 1660-1600, 1400-1200 and 1100-1000 cm(-1). For curve fitting, the results showed the differences in the protein secondary structures and the polysaccharide structures/content between broken cellular wall G. lucidum spores and G. lucidum spores. Moreover, the value of A1078/A1741 might be a potentially useful factor to distinguish broken cellular wall G. lucidum spores from G. lucidum spores. Additionally, FTIR microspectroscopy could identify broken cellular wall G. lucidum spores and G. lucidum spores accurately when it was combined with hierarchical cluster analysis. The result suggests FTIR microspectroscopy is very simple and efficient for distinction of broken cellular wall G. lucidum spores and G. lucidum spores. The result also indicates FTIR microspectroscopy may be useful for TCM identification.