An ancestral NB-LRR with duplicated 3'UTRs confers stripe rust resistance in wheat and barley.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a global threat to wheat production. Aegilops tauschii, one of the wheat progenitors, carries the YrAS2388 locus for resistance to Pst on chromosome 4DS. We reveal that YrAS2388 encodes a typical nucleotide oligomerization domain-like receptor (NLR). The Pst-resistant allele YrAS2388R has duplicated 3' untranslated regions and is characterized by alternative splicing in the nucleotide-binding domain. Mutation of the YrAS2388R allele disrupts its resistance to Pst in synthetic hexaploid wheat; transgenic plants with YrAS2388R show resistance to eleven Pst races in common wheat and one race of P. striiformis f. sp. hordei in barley. The YrAS2388R allele occurs only in Ae. tauschii and the Ae. tauschii-derived synthetic wheat; it is absent in 100% (n = 461) of common wheat lines tested. The cloning of YrAS2388R will facilitate breeding for stripe rust resistance in wheat and other Triticeae species

Single-cell ligand–receptor profiling reveals an immunotherapy-responsive subtype and prognostic signature in triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is an aggressive form of cancer that lacks specific targeted therapies. Although ligand–receptor (LR) interactions play a crucial role in intercellular communication and contribute to tumor heterogeneity, their molecular details and potential as prognostic or predictive markers in TNBC have not been thoroughly investigated.MethodsWe analyzed single-cell RNA sequencing data to categorize TNBC into 12 subgroups and 10 distinct cell types. From this dataset, we identified LR pairs that exhibited significant intercellular crosstalk and evaluated their prognostic relevance in a METABRIC TNBC cohort (n = 298). Through consensus clustering of these LR pairs, two molecular subtypes were defined. Key LR genes were then selected using Lasso regression and stepwise multivariate analysis to build an LR-based prognostic scoring system (LR.score), which was validated using both the METABRIC and GSE58812 datasets (n = 107). Additionally, we performed siRNA-mediated knockdown of the CXCL9/CXCR3 axis in MDA-MB-231 cells, confirming the knockdown via RT-qPCR and Western blot. The functional impact was assessed through proliferation, colony formation, and wound healing assays.ResultsOne subtype (Clust1) demonstrated strong immune cell infiltration, higher immune scores, and enrichment in pathways such as epithelial–mesenchymal transition, angiogenesis, and KRAS signaling—indicative of a basal-like, immune-active phenotype. Among the LR pairs, the CXCL9–CXCR3 axis was identified as a key factor in immune cell recruitment and anti-tumor responses. Functionally, silencing the CXCL9/CXCR3 axis significantly diminished the proliferation, colony formation, and migratory capabilities of MDA-MB-231 cells. Moreover, a higher LR.score was correlated with poorer overall survival (HR = 1.69, 95% CI = 1.12–2.56, P < 0.05) and reduced response to immune checkpoint inhibitors (ICIs), while patients with lower LR.score showed increased sensitivity to ICIs, particularly in anti–PD-L1 cohorts.ConclusionThe LR.score serves as an independent prognostic factor and a reliable predictor of immunotherapy response in TNBC. Targeting crucial LR interactions, especially the CXCL9–CXCR3 axis, may enhance immunotherapeutic efficacy and refine prognostic evaluations, paving the way for improved treatment strategies in TNBC

Case Report: Two cases of advanced primary cardiac angiosarcoma treated with anlotinib and a retrospective analysis of the literature

Primary cardiac angiosarcoma is a rare malignant soft-tissue sarcoma derived from vascular endothelial cells or lymphatic endothelial cells, with a high malignancy, poor prognosis, and a lack of effective medical therapy. This article reports on two patients with primary cardiac angiosarcoma who received first-line treatment with multi-targeted anti-angiogenic agent, anlotinib monotherapy. The treatment rapidly controlled pleural and pericardial effusion, significantly reduced the tumor, improved symptoms, and showed satisfactory recent efficacy. This indicates that anlotinib offers a new first-line treatment option for advanced primary cardiac angiosarcoma

Mendelian randomization shows causal effects of birth weight and childhood body mass index on the risk of frailty

BackgroundThe association between birth weight and childhood body mass index (BMI) and frailty has been extensively studied, but it is currently unclear whether this relationship is causal.MethodsWe utilized a two-sample Mendelian randomization (MR) methodology to investigate the causal effects of birth weight and childhood BMI on the risk of frailty. Instrumental variables (p < 5E-08) strongly associated with own birth weight (N = 298,142 infants), offspring birth weight (N = 210,267 mothers), and childhood BMI (N = 39,620) were identified from large-scale genomic data from genome-wide association studies (GWAS). The frailty status was assessed using the frailty index, which was derived from comprehensive geriatric assessments of older adults within the UK Biobank and the TwinGene database (N = 175,226).ResultsGenetically predicted one standard deviation (SD) increase in own birth weight, but not offspring birth weight (maternal-specific), was linked to a decreased frailty index (β per SD increase = −0.068, 95%CI = −0.106 to −0.030, p = 3.92E-04). Conversely, genetically predicted one SD increase in childhood BMI was associated with an elevated frailty index (β per SD increase = 0.080, 95%CI = 0.046 to 0.114, p = 3.43E-06) with good statistical power (99.8%). The findings remained consistent across sensitivity analyses and showed no horizontal pleiotropy (p > 0.05).ConclusionThis MR study provides evidence supporting a causal relationship between lower birth weight, higher childhood BMI, and an increased risk of frailty

Clinical characteristics of severe influenza as a risk factor for febrile seizures in children: a retrospective analysis

ObjectiveTo retrospectively analyze the clinical characteristics and independent risk factors of severe influenza combined with febrile seizures, and to provide more basis for early clinical intervention.MethodsA total of 161 children with severe influenza were collected as study subjects and divided into convulsive (FC) group (40 cases) and non-convulsive (NFC) group (121 cases) according to whether they had febrile seizures. The demographic characteristics and clinical data of the two groups were analyzed. Multivariate logistic regression was used to analyze the risk factors of severe influenza combined with febrile seizures. The predictive efficacy was evaluated by receiver operating characteristic (ROC) curve analysis.Results(1) Multiple logistic regression analysis revealed that C-reactive protein (CRP) levels, Serum interleukin 6 (IL-6) levels, Days from onset of Flu symptoms to hospitalization, cerebrospinal fluid protein (CSF-TP) levels and the influenza virus type A (FluA) infection rate were found to be independent risk factors for severe influenza combined with febrile seizures in children. (2) ROC curve analysis showed that the cut-off value of CRP, Serum IL-6, Days from onset of Flu symptoms to hospitalization and CSF-TP were 7.57 mg/L, 9.84 pg/ml, 4.5 days and 194.8 mg/L, respectively.ConclusionChildren with severe influenza with CRP ≥ 7.57 mg/L, Serum IL-6 ≥ 9.84 pg/ml, Days from onset of Flu symptoms to hospitalization ≤4.5 days, CSF-TP ≥ 194.8 mg/L and FluA had a significantly increased risk of febrile seizures. It is useful for clinicians to determine the risk of severe influenza combined with febrile seizures, to adjust the early treatment plan, and to reduce the incidence of critically ill patients

Evaluation of the Antioxidative, Antibacterial, and Anti-Inflammatory Effects of the Aloe

Little work is done to develop Aloe vera (AV) using probiotics. To explore the potential benefits, the antioxidant effects and the antibacterial effects on foodborne pathogens of Aloe fermentation supernatant were evaluated in vitro. Our results indicated that the Aloe fermentation supernatant fermented by Lactobacillus plantarum HM218749.1 had very strong scavenging capacities of the DPPH (86%), O2•- (85%), OH• (76%), and Fe2+ chelation (82%) and reducing powers (242.5 mg/L), and the inhibition zones for Salmonella typhimurium, Salmonella enteritidis, Shigella flexneri, Escherichia coli, Listeria monocytogenes, S. dysenteriae 301, Staphylococcus aureus Cowan1, and Propionibacterium acnes were 16, 15, 19, 20, 21, 20, and 27 mm. Moreover, the low concentration of Aloe fermentation supernatant had significantly reduced the production of IL-1β, TNF-α, and IL-6 in both mRNA and protein levels (P<0.01). Therefore, the Aloe fermentation supernatant can be used as functional beverage or cosmetic ingredients to guard human intestinal health, delaying senescence, and prevent chronic diseases

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

Background/Aims: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. Materials: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. Results: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P&#x3c; 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P&#x3c; 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P&#x3c; 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. Conclusion: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer

Necrotizing pneumonia and purulent meningitis caused by bloodstream infection of CA-MRSA in a child: A rare case report

Case presentationWe report the case of a girl aged 2 years and 10 months who had fever for 2 days, vomiting, poor mental status for 1 day, and one episode of convulsions.Symptoms and signsThe patient experienced a rapid onset of symptoms with fever, vomiting, and convulsions. Upon physical examination on admission, she presented with the following: temperature 38.6°C; pulse 185 beats/min; respiration 49 beats/min; blood pressure 89/51 mmHg; drowsiness; piebald skin all over her body; rice-grain-sized pustular rashes scattered on the front chest and both lower limbs, protruding from the surface of the skin; bilateral pupils that were equal in size and a circle with a diameter of about 3.0 mm, and slow light reflex; cyanotic lips; shortness of breath; positive for the three-concave sign; a small amount of phlegm that could be heard in both lungs; capillary refill time of 5 s; cold extremities; and a positive Babinski sign.Diagnostic methodA chest computed tomography scan showed multiple nodular and flake-like high-density shadows of varying sizes in each lobe in bilateral lungs, and a cavity with blurred edges could be seen in some nodules. A cranial magnetic resonance imaging examination demonstrated that the hyperintensity of diffusion-weighted imaging could be observed on the left cerebellar hemisphere and left parietal blade. Blood cultures, sputum, cerebrospinal fluid, and bronchoalveolar lavage fluid (BALF) by fiberoptic bronchoscopy all indicated the growth of methicillin-resistant Staphylococcus aureus (MRSA).Treatment methodsAfter admission, the child was given meropenem combined with vancomycin, cefoperazone sulbactam combined with rifamycin, linezolid (oral) for anti-infection successively, and other adjuvant therapies.Clinical outcomesThe patient recovered clinically and was discharged from our hospital.Recommended readersNeurology; Respiratory Medicine; Infectious Diseases Department