An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure.

The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher the immune dynamics during human LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B cells, and dysfunctional CD8+ T cells increase during tumor initiation/invasion and form a tertiary lymphoid structure (TLS) inside the tumor. This TLS starts with an aggregation of CD4+ T cells and the generation of CXCL13-expressing Tfh-like cells, followed by an accumulation of B cells, and then forms a CD4+ T and B cell aggregate. TLS and its associated cells are correlated with better patient survival. Inhibiting TLS formation by Tfh or B cell depletion promotes tumor growth in mouse models. The anti-tumoral effect of the Tfh-dependent TLS is mediated through interleukin-21 (IL-21)-IL-21 receptor signaling. Our study establishes an anti-tumoral role of the Tfh-dependent TLS in the development of LUAD.

An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development.

Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA sequencing map of the dynamics of human macrophage specification from PCW 4-26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart. They are the major immune population in the early epidermis, exhibit a polarized distribution along the dorsal-lateral-ventral axis, and interact with neural crest cells, modulating their differentiation along the melanocyte lineage. Through spatial and differentiation trajectory analysis, we also showed that proangiogenic macrophages are perivascular across fetal organs and likely yolk-sac-derived as microglia. Our study provides a comprehensive map of the heterogeneity and developmental dynamics of human macrophages and unravels their diverse functions during development.

Functional properties and antioxidant activity of gelatine and hydrolysate from deer antler base.

Gelatine was extracted from deer antler base by the hot water method and hydrolyzed with trypsin. A comparison of the properties of gelatine before and after enzymatic hydrolysis showed a decline in the surface hydrophobicity, enhanced thermal stability, broadening of the particle size distribution, a zeta potential shift to a lower pH, reduced foaming and emulsifying properties, and enhanced antioxidant activity. Hydrolysis increased the gelatine antioxidant activity in DPPH and FRAP assays. These results indicate that the functional properties of deer antler base gelatine may be affected by trypsin modification.

Clinical course and treatment efficacy of COVID-19 near Hubei Province, China: A multicentre, retrospective study.

Currently, COVID-19 has been reported in nearly all countries globally. To date, little is known about the viral shedding duration, clinical course and treatment efficacy of COVID-19 near Hubei Province, China. This multicentre, retrospective study was performed in 12 hospitals in Henan and Shaanxi Provinces from 20 January to 8 February 2020. Clinical outcomes were followed up until 26 March 2020. The viral shedding duration, full clinical course and treatment efficacy were analysed in different subgroups of patients. A total of 149 COVID-19 patients were enrolled. The median age was 42 years, and 61.1% (91) were males. Of them, 133 (89.3%) had fever, 131 of 144 (91%) had pneumonia, 27 (18.1%) required intensive care unit (ICU) management, 3 (2%) were pregnant, and 3 (2%) died. Two premature newborns were negative for SARS-CoV-2. In total, the median SARS-CoV-2 shedding period and clinical course were 12 (IQR: 9-17; mean: 13.4, 95% CI: 12.5, 14.2) and 20 (IQR: 16-24; mean: 21.2, 95% CI: 20.1, 22.3) days, respectively, and ICU patients had longer median viral shedding periods (21 [17-24] versus 11 [9-15]) and clinical courses (30 [22-33] vs. 19 [15.8-22]) than non-ICU patients (both p < .0001). SARS-CoV-2 clearances occurred at least 2 days before fatality in 3 non-survivors. Current treatment with any anti-viral agent or combination did not present the benefit of shortening viral shedding period and clinical course (all p > .05) in real-life settings. In conclusion, the viral shedding duration and clinical course in Henan and Shaanxi Provinces were shorter than those in Hubei Province, and current anti-viral therapies were ineffective for shortening viral shedding duration and clinical course in real-world settings. These findings expand our knowledge of the SARS-CoV-2 infection and may be helpful for management of the epidemic outbreak of COVID-19 worldwide. Further studies concerning effective anti-viral agents and vaccines are urgently needed.

Effect of Convalescent Plasma Therapy on Viral Shedding and Survival in Patients With Coronavirus Disease 2019.

Currently, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported in almost all countries globally. No effective therapy has been documented for COVID-19, and the role of convalescent plasma therapy is unknown. In the current study, 6 patients with COVID-19 and respiratory failure received convalescent plasma a median of 21.5 days after viral shedding was first detected, all tested negative for SARS-CoV-2 RNA within 3 days after infusion, and 5 eventually died. In conclusion, convalescent plasma treatment can end SARS-CoV-2 shedding but cannot reduce the mortality rate in critically ill patients with end-stage COVID-19, and treatment should be initiated earlier.

Effects of different substrates on low-temperature storage of fresh ginseng.

BACKGROUND: Fresh ginseng was buried in three types of sand with different moisture contents and three types of soil and then stored at 2 °C to determine the effects of these storage substrates on fresh ginseng. RESULTS: At a storage time of 200 days, ginseng stored in underforest soil softened the most slowly and had a significantly greater firmness compared to the other samples (P < 0.05). The amount of most ginsenosides changed after storage for most of the substrates. Samples stored in ginseng soil and biological fertilizer had the highest concentration of total saponin and ginseng polysaccharides, respectively. Fresh ginseng stored in medium-water content sand had a significantly lower polyphenol oxidase activity (P < 0.05). A significant difference was observed in the total concentration of nucleosides and nucleobases between the ginseng samples stored with and without substrates (P < 0.05). CONCLUSION: The data obtained in the present study suggest that the use of storage substrates is an optimal method for extending the shelf life of fresh ginseng without detrimental effects on its components. © 2019 Society of Chemical Industry.

Quantification of Furosine (Nε-(2-Furoylmethyl)-l-lysine) in Different Parts of Velvet Antler with Various Processing Methods and Factors Affecting Its Formation.

Furosine (Nε-(2-furoylmethyl)-l-lysine) is formed during the early stages of the Maillard reaction from a lysine Amadori compound and is frequently used as a marker of reaction progress. Furosine is toxic, with significant effects on animal livers, kidneys, and other organs. However, reports on the formation of furosine in processed velvet antler are scarce. In this study, we have quantified the furosine content in processed velvet antler by using UPLC-MS/MS. The furosine contents of velvet antler after freeze-drying, boiling, and processing without and with blood were 148.51⁻193.93, 168.10⁻241.22, 60.29⁻80.33, and 115.18⁻138.99 mg/kg protein, respectively. The factors affecting furosine formation in processed velvet antler, including reducing sugars, proteins, amino acids, and process temperature, are discussed herein. Proteins, amino acids, and reducing sugars are substrates for the Maillard reaction and most significantly influence the furosine content in the processed velvet antler. High temperatures induce the production of furosine in boiled velvet antler but not in the freeze-dried samples, whereas more furosine is produced in velvet antler processed with blood, which is rich in proteins, amino acids, and reducing sugars, than in the samples processed without blood. Finally, wax slices rich in proteins, amino acids, and reducing sugars produced more furosine than the other parts of the velvet antler. These data provide a reference for guiding the production of low-furosine velvet antler and can be used to estimate the consumer intake of furosine from processed velvet antler.