Minimal residual disease profiling predicts pathological complete response in esophageal squamous cell carcinoma.

Accurate presurgical prediction of pathological complete response (pCR) can guide treatment decisions, potentially avoiding unnecessary surgeries and improving the quality of life for cancer patients. We developed a minimal residual disease (MRD) profiling approach with enhanced sensitivity and specificity for detecting minimal tumor DNA from cell-free DNA (cfDNA). The approach was validated in two independent esophageal squamous cell carcinoma (ESCC) cohorts. In a cohort undergoing neoadjuvant, surgical, and adjuvant therapy (NAT cohort), presurgical MRD status precisely predicted pCR. All MRD-negative cases (10/10) were confirmed as pCR by pathological evaluation on the resected tissues. In contrast, MRD-positive cases included all the 27 non-pCR cases and only one pCR case (10/10 vs 1/28, P < 0.0001, Fisher's exact test). In a definitive radiotherapy cohort (dRT cohort), post-dRT MRD status was closely correlated with patient prognosis. All MRD-negative patients (25/25) remained progression-free during the follow-up period, while 23 of the 26 MRD-positive patients experienced disease progression (25/25 vs 3/26, P < 0.0001, Fisher's exact test; progression-free survival, P < 0.0001, log-rank test). The MRD profiling approach effectively predicted the ESCC patients who would achieve pCR with surgery and those likely to remain progression-free without surgery. This suggests that the cancer cells in these MRD-negative patients have been effectively eliminated and they could be suitable candidates for a watch-and-wait strategy, potentially avoiding unnecessary surgery.

Origin, loss, and regain of self-incompatibility in angiosperms.

The self-incompatibility (SI) system with the broadest taxonomic distribution in angiosperms is based on multiple S-locus F-box genes (SLFs) tightly linked to an S-RNase termed type-1. Multiple SLFs collaborate to detoxify nonself S-RNases while being unable to detoxify self S-RNases. However, it is unclear how such a system evolved, because in an ancestral system with a single SLF, many nonself S-RNases would not be detoxified, giving low cross-fertilization rates. In addition, how the system has been maintained in the face of whole-genome duplications (WGDs) or lost in other lineages remains unclear. Here we show that SLFs from a broad range of species can detoxify S-RNases from Petunia with a high detoxification probability, suggestive of an ancestral feature enabling cross-fertilization and subsequently modified as additional SLFs evolved. We further show, based on its genomic signatures, that type-1 was likely maintained in many lineages, despite WGD, through deletion of duplicate S-loci. In other lineages, SI was lost either through S-locus deletions or by retaining duplications. Two deletion lineages regained SI through type-2 (Brassicaceae) or type-4 (Primulaceae), and one duplication lineage through type-3 (Papaveraceae) mechanisms. Thus, our results reveal a highly dynamic process behind the origin, maintenance, loss, and regain of SI.

Inferring Chinese surnames with Y-STR profiles.

Co-ancestry of human surnames and Y-chromosomes in most human populations and social groups suggests the possibility of inferring one from the other. However, such an intuitive perspective remains to be formally explored. In the present study, we develop two computational methods, based on cosine distance (dcos) and coalescence distance (dcoal) respectively, to infer surnames from Y-STR profiles. We also survey Y-STR variations at 15 loci for 19,009 individuals of Shandong Province in China. For a total of 266 surnames included in the data set, our methods can pinpoint to a single surname with an average accuracy of 65%, and with an average accuracy higher than 80% when providing >4 candidate surnames. We also demonstrate that increasing the sample size of surnames and the number of STR loci improves the accuracy of surname inference. Our results indicate that the 15 non-duplicated Y-STR loci contain information from which surname can be reliably inferred for Chinese populations, showing a promising application in forensics.

Deferoxamine ameliorates hepatosteatosis via several mechanisms in ob/ob mice.

Hepatic iron accumulation may be responsible for the pathology of nonalcoholic fatty liver disease (NAFLD), which is both increasingly prevalent in conjunction with obesity and associated with comorbidities. The efficacy of iron reduction therapies, such as phlebotomy or dietary iron restriction, has been demonstrated in patient and animal models, including models of diabetes and obesity; however, the effects on and exact mechanisms responsible for iron depletion in NAFLD have not been clearly elucidated. Our study investigated the role of iron depletion by deferoxamine (DFO) treatment of ob/ob mice with hepatic steatosis. We found that DFO reduced hepatic iron deposition and regulated intracellular iron concentration in a homeostatic process following 15 days of treatment. Compared with vehicle treatment, DFO significantly improved hepatic steatosis by upregulating proteins related to lipid metabolism. Meanwhile, the reduction of free radical formation and proinflammatory cytokines, as well as the increase of hypoxia-inducible factor-1α pathway proteins and Bcl2/Bax ratio, further indicated that DFO was effective for liver protection and hepatic adaptation. These findings show that the intraperitoneal delivery of DFO provides a potential means of both preventing the progression of NAFLD and accelerating healing of hepatic steatosis, with the potential for rapid clinical application.