scRNA-seq revealed the special TCR ß & α V(D)J allelic inclusion rearrangement and the high proportion dual (or more) TCR-expressing cells.

Allelic exclusion, one lymphocyte expresses one antigen receptor, is a fundamental mechanism of immunological self-tolerance and highly specific immune responses to pathogens. However, the phenomenon of V(D)J allelic inclusion (incomplete allelic exclusion or allelic escape) rearrangement and dual TCR T cells have been discovered by multiple laboratories. Despite continuous new discoveries, the proportion and underlying mechanism of dual TCR has been puzzling immunologists. In this study, we observed the presence of single T cells expressing multiple TCR chains in all samples, with the proportion of 15%, 10%, and 20% in the human thymus, human peripheral blood, and mouse lymphoid organs, respectively. The proportion of T cells possessing multiple T-cell receptors (TCR) varied significantly in different physiological states and developmental stages. By analyzing RSS category, RSS direction, and V(D)J gene position at TR locus of T cells which contain multiple TCR chains, we creatively found that one of TCR ß (or TCR α) should originate from the transcription of V(D)J combination in T-cell receptor excision circle (TREC) formed after the twice successful rearrangement in the same chromosome. Moreover, human V30 (or mouse V31) gene may participate in reverse recombination and transcription to prevent allelic exclusion. In general, high proportion of T cells with multiple TCR at the transcriptome level was first made public, and we proposed a novel mechanism of secondary (or more) TCR rearrangement on a single chromosome. Our findings also indicated that the single-cell sequencing data should be classified according to the single, multiple, and abnormal TCR when analyzing the T-cell repertoire.

New insights into the germline genes and CDR3 repertoire of the TCRß chain in Chiroptera.

Introduction: Bats are recognized as natural reservoirs for many viruses, and their unique immune system enables them to coexist with these viruses without frequently exhibiting disease symptoms. However, the current understanding of the bat adaptive immune system is limited due to the lack of a database or tool capable of processing T-cell receptor (TCR) sequences for bats. Methods: We performed germline gene annotation in three bat species using homologous genes and RSSs (Recombinational Signal Sequences) scanning method. Then we used the conserved C gene to construct the TCRß chain receptor library of the Intermediate Horseshoe Bat. Bats' TCRß data will be analyzed using MiXCR and constructed reference library. Results: Regarding the annotation results, we found that the Pale Spear-nosed Bat has 37 members in the TRBV12 family, which is more than the total number of TRBV genes in the Greater Horseshoe Bat. The average number of unique TCRß chain receptor sequences in each Intermediate Horseshoe Bat sample reached 24,904. Discussion: The distinct variations in the distribution of TRBV genes among the three types of bats could have a direct impact on the diversity of the TCR repertoire, as evidenced by the presence of conserved amino acids that indicate the T-cell recognition of antigens in bats is MHC-restricted. The bats' TCRß repertoire is formed through the rearrangement of the V-D-J-C genes, with D-J/V-D deletions and insertions resulting in high diversity.

Activated SOX9+ renal epithelial cells promote kidney repair through secreting factors.

A broad spectrum of lethal kidney diseases involves the irreversible destruction of the tubular structures, leading to renal function loss. Following injury, a spectrum of tissue-resident epithelial stem/progenitor cells are known to be activated and then differentiate into mature renal cells to replace the damaged renal epithelium. Here, however, we reported an alternative way that tissue-resident cells could be activated to secrete multiple factors to promote organ repair. At single-cell resolution, we showed that the resident SOX9+ renal epithelial cells (RECs) could expand in the acutely injured kidney of both mouse and human. Compared to other cells, the SOX9+ RECs overexpressed much more secretion related genes, whose functions were linked to kidney repair pathways. We also obtained long-term, feeder-free cultured SOX9+ RECs from human urine and analysed their secretory profile at both transcriptional and proteomic levels. Engraftment of cultured human SOX9+ RECs or injection of its conditional medium facilitated the regeneration of renal tubular and glomerular epithelium, probably through stimulating endogenous REC self-activation and mediating crosstalk with other renal cells. We also identified S100A9 as one of the key factors in the SOX9+ REC secretome. Altogether, the abilities to extensively propagate SOX9+ RECs in culture whilst concomitantly maintaining their intrinsic secretory capacity suggest their future application in cell-free therapies and regeneration medicine.

The Effect of Strict Lockdown on Omicron SARS-CoV-2 Variant Transmission in Shanghai.

Omicron, the current SARS-CoV-2 variant of concern, is much more contagious than other previous variants. Whether strict lockdown could effectively curb the transmission of Omicron is largely unknown. In this retrospective study, we compared the strictness of government lockdown policies in Shanghai and other countries. Based on the daily Omicron case number from 1 March 2022 to 30 April 2022, the effective reproductive numbers in this Shanghai Omicron wave were calculated to confirm the impact of strict lockdown on Omicron transmission. Pearson correlation was conducted to illustrate the determining factor of strict lockdown outcomes in the 16 different districts of Shanghai. After a very strict citywide lockdown since April 1st, the average daily effective reproductive number reduced significantly, indicating that strict lockdown could slow down the spreading of Omicron. Omicron control is more challenging in districts with higher population mobility and lockdown is more likely to decrease the number of asymptomatic carriers than the symptomatic cases. All these findings indicate that the strict lockdown could curb the transmission of Omicron effectively, especially for the asymptomatic spread, and suggest that differentiated COVID-19 prevention and control measures should be adopted according to the population density and demographic composition of each community.

Case report: Fully endoscopic microvascular decompression for glossopharyngeal neuralgia.

With the advances in endoscopic technology, endoscopy is widely used in many neurosurgical procedures, such as microvascular decompression, which is an effective method to treat glossopharyngeal neuralgia, trigeminal neuralgia, and facial spasm. The purpose of this study was to determine the efficacy of fully endoscopic microvascular decompression in the treatment of glossopharyngeal neuralgia. We managed a patient with glossopharyngeal neuralgia in our department, whose main clinical manifestation was recurrent left ear and facial pain for 3 years. The patient underwent a fully endoscopic microvascular decompression. The pain in the left ear and face was significantly relieved postoperatively, and there was no recurrence at the 6-month follow-up evaluation. We describe a case of glossopharyngeal neuralgia that was successfully treated by fully endoscopic microvascular decompression, which showed that endoscopy has advantages in microvascular decompression, and fully endoscopic microvascular decompression is an effective method for glossopharyngeal neuralgia.