Mapping and characterization of rust resistance genes Lr53 and Yr35 introgressed from Aegilops species.

KEY MESSAGE: The rust resistance genes Lr53 and Yr35 were introgressed into bread wheat from Aegilops longissima or Aegilops sharonensis or their S-genome containing species and mapped to the telomeric region of chromosome arm 6BS. Wheat leaf and stripe rusts are damaging fungal diseases of wheat worldwide. Breeding for resistance is a sustainable approach to control these two foliar diseases. In this study, we used SNP analysis, sequence comparisons, and cytogenetic assays to determine that the chromosomal segment carrying Lr53 and Yr35 was originated from Ae.longissima or Ae. sharonensis or their derived species. In seedling tests, Lr53 conferred strong resistance against all five Chinese Pt races tested, and Yr35 showed effectiveness against Pst race CYR34 but susceptibility to race CYR32. Using a large population (3892 recombinant gametes) derived from plants homozygous for the ph1b mutation obtained from the cross 98M71 × CSph1b, both Lr53 and Yr35 were successfully mapped to a 6.03-Mb telomeric region of chromosome arm 6BS in the Chinese Spring reference genome v1.1. Co-segregation between Lr53 and Yr35 was observed within this large mapping population. Within the candidate region, several nucleotide-binding leucine-rich repeat genes and protein kinases were identified as candidate genes. Marker pku6B3127 was completely linked to both genes and accurately predicted the absence or presence of alien segment harboring Lr53 and Yr35 in 87 tetraploid and 149 hexaploid wheat genotypes tested. We developed a line with a smaller alien segment (< 6.03 Mb) to reduce any potential linkage drag and demonstrated that it conferred resistance levels similar to those of the original donor parent 98M71. The newly developed introgression line and closely linked PCR markers will accelerate the deployment of Lr53 and Yr35 in wheat breeding programs.

ANKRD2 expression combined with TNFRSF19 expression for evaluating the prognosis of oral squamous cell carcinoma patients.

Objective: As an important chemotherapy drug, cisplatin has been widely used in the treatment of many cancers. However, many patients, including oral squamous cell carcinoma (OSCC) patients, experience unacceptable outcomes from cisplatin treatment. Thus, we devised a risk model for predicting the sensitivity of OSCC patients to cisplatin treatment, to provide a reference for clinical practice. Methods: CAL-27 and SCC-9 cell lines treated or not with cisplatin and data from The Cancer Genome Atlas (TCGA) were screened for simultaneously and significantly differentially expressed genes. Next, we built a risk model for predicting cisplatin sensitivity in OSCC patients. Reverse transcription-polymerase chain reaction (RT-PCR), pathological samples and clinical data were used to examine the reliability of the model. Results: ANKRD2 and TNFRSF19 were differentially expressed between the OSCC metastasis cell line HSC-3 treated and not treated with cisplatin, as well as between the OSCC cell line SCC-25 and the cell line SCC25-DDP, which has cisplatin chemoresistance. We found that the expression of ANKRD2 and TNFRSF19 had a significant influence on the prognosis of OSCC patients. The risk model that combined ANKRD2 and TNFRSF19 to predict sensitivity to cisplatin in OSCC patients was confirmed by analysing the pathological samples and follow-up information of clinical patients. Conclusions: The expression of ANKRD2 and TNFRSF19 is associated with cisplatin sensitivity and prognosis in patients with OSCC. The survival outcome of patients with oral squamous cell carcinoma (OSCC) was found to be significantly worse in those with high expression of ANKRD2 combined with low expression of TNFRSF19. ANKRD2 and TNFRSF19 may be targets for cisplatin sensitivity prediction in OSCC patients. These findings may provide novel strategies for overcoming cisplatin resistance.

AURKB promotes immunogenicity and immune infiltration in clear cell renal cell carcinoma.

BACKGROUND: Chromatin regulators (CRs) are capable of causing epigenetic alterations, which are significant features of cancer. However, the function of CRs in controlling Clear Cell Renal Cell Carcinoma (ccRCC) is not well understood. This research aims to discover a CRs prognostic signature in ccRCC and to elucidate the roles of CRs-related genes in tumor microenvironment (TME). METHODS: Expression profiles and relevant clinical annotations were retrieved from the Cancer Genome Atlas (TCGA) and UCSC Xena platform for progression-free survival (PFS) data. The R package "limma" was used to identify differentially expressed CRs. A predictive model based on five CRs was developed using LASSO-Cox analysis. The model's predictive power and applicability were validated using K-M curves, ROC curves, nomograms, comparisons with other models, stratified survival analyses, and validation with the ICGC cohort. GO and GSEA analyses were performed to investigate mechanisms differentiating low and high riskScore groups. Immunogenicity was assessed using Tumor Mutational Burden (TMB), immune cell infiltrations were inferred, and immunotherapy was evaluated using immunophenogram analysis and the expression patterns of human leukocyte antigen (HLA) and checkpoint genes. Differentially expressed CRs (DECRs) between low and high riskScore groups were identified using log2|FC|> 1 and FDR < 0.05. AURKB, one of the high-risk DECRs and a component of our prognostic model, was selected for further analysis. RESULTS: We constructed a 5 CRs signature, which demonstrated a strong capacity to predict survival and greater applicability in ccRCC. Elevated immunogenicity and immune infiltration in the high riskScore group were associated with poor prognosis. Immunotherapy was more effective in the high riskScore group, and certain chemotherapy medications, including cisplatin, docetaxel, bleomycin, and axitinib, had lower IC50 values. Our research shows that AURKB is critical for the immunogenicity and immune infiltration of the high riskScore group. CONCLUSION: Our study produced a reliable prognostic prediction model using only 5 CRs. We found that AURKB promotes immunogenicity and immune infiltration. This research provides crucial support for the development of prognostic biomarkers and treatment strategies for ccRCC.

Ultralow-cost piezoelectric sensor constructed by thermal compression bonding for long-term biomechanical signal monitoring in chronic mental disorders.

Wearable bioelectronic devices, which circumvent issues related to the large size and high cost of clinical equipment, have emerged as powerful tools for the auxiliary diagnosis and long-term monitoring of chronic psychiatric diseases. Current devices often integrate multiple intricate and expensive devices to ensure accurate diagnosis. However, their high cost and complexity hinder widespread clinical application and long-term user compliance. Herein, we developed an ultralow-cost poly(vinylidene fluoride)/zinc oxide nanofiber film-based piezoelectric sensor in a thermal compression bonding process. Our piezoelectric sensor exhibits remarkable sensitivity (13.4 mV N-1), rapid response (8 ms), and exceptional stability over 2000 compression/release cycles, all at a negligibly low fabrication cost. We demonstrate that pulse wave, blink, and speech signals can be acquired by the sensor, proposing a single biomechanical modality to monitor multiple physiological traits associated with bipolar disorder. This ultralow-cost and mass-producible piezoelectric sensor paves the way for extensive long-term monitoring and immediate feedback for bipolar disorder management.

Mulberry and Hippophae-based solid beverage attenuate hyperlipidemia and hepatic steatosis via adipose tissue-liver axis.

Dyslipidemia and hepatic steatosis are the characteristics of the initial stage of nonalcohol fatty liver disease (NAFLD), which can be reversed by lifestyle intervention, including dietary supplementation. However, such commercial dietary supplements with solid scientific evidence and in particular clear mechanistic elucidation are scarce. Here, the health benefits of MHP, a commercial mulberry and Hippophae-based solid beverage, were evaluated in NAFLD rat model and the underlying molecular mechanisms were investigated. Histopathologic examination of liver and white adipose tissue found that MHP supplementation reduced hepatic lipid accumulation and adipocyte hypertrophy. Serum biochemical results confirmed that MHP effectively ameliorated dyslipidemia and decreased circulation-free fatty acid level. RNA-Seq-based transcriptomic analysis showed that MHP-regulated genes are involved in the inhibition of lipolysis of adipose tissue and thus may contribute to the reduction of hepatic ectopic lipid deposition. Furthermore, MHP upregulated ACSL1-CPT1a-CPT2 pathway, a canonical pathway that regulated mitochondrial fatty acid metabolism, and promoted liver and adipose tissue fatty acid ß-oxidation. These results suggest that adipose tissue-liver crosstalk may play a key role in maintaining glucose and lipid metabolic hemostasis. In addition, MHP can also ameliorate chronic inflammation through regulating the secretion of adipokines. Our study demonstrates that MHP is able to improve dyslipidemia and hepatic steatosis through crosstalk between adipose tissue and liver and also presents transcriptomic evidence to support the underlying mechanisms of action, providing solid evidence for its health claims.

Mulberry and Hippophae-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling.

Obesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.