Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops.

The Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.

Prevalence and Genetic Analysis of ß-Thalassemia in the Dali Bai Autonomous Prefecture of the Yunnan Province, China.

Background: ß-Thalassemia is the most common monogenetic hemolytic hemoglobin-associated disease in the south of China; the distribution of genetic mutations associated with this condition varies according to geographic regions. This study investigated the prevalence and distribution of ß-thalassemia-associated mutations across different ethnic groups in the Dali Bai Autonomous Prefecture of the Yunnan Province, China. Methods: This cross-sectional study included 4723 participants (15-45 years old) who volunteered for thalassaemia screening from the Dali Bai Autonomous Prefecture from May 2017 to October 2020. Cellulose acetate membrane electrophoresis was used to screen for ß-thalassemia carriers. Genotypic analyses was performed using polymerase chain reaction-based reverse dot blotting and DNA sequencing. Results: The overall prevalence of ß-thalassemia in the study population was 2.01%. The genotypic analyses showed the presence of four types of mutations in the ß-globin gene: CD26 (GAG→AAG), CD56 (GGC→GAC), IVS-II-81 (C→T), and CD121 (GAA→CAA). In contrast to previous studies from other regions of Yunnan Province, our results showed that the prevalence of CD26 mutations was significantly higher than that of the other mutations. Conclusion: Our data suggests that the Dali Autonomous Prefecture is an area with a high prevalence of ß-thalassemia. Moreover, CD26 was the only ß-thalassemia mutation that we have detected. Moreover, the vast majority of the ß-thalassemia mutations observed were CD26.

Prognostic Value of Combined Lactate Dehydrogenase, C-Reactive Protein, Cancer Antigen 153 and Cancer Antigen 125 in Metastatic Breast Cancer.

BACKGROUND: Breast cancer (BC), especially metastatic BC, is one of the most lethal diseases in women. CA 125 and CA 15-3 are commonly used indicators for diagnosis and prognosis of BC. Some serological indicators, such as lactate dehydrogenase (LDH) and C-reactive protein (CRP), can also be used to assess the prognosis and progression in BC. METHODS: Univariate Cox regression analysis and LASSO regression analysis were performed to identify prognostic factors and build prognostic models. We distributed the patients into 2 groups based on the median risk score, analyzed prognosis by Kaplan-Meier curve, and screened independent prognostic factors by multivariate Cox regression analysis. RESULT: We identified 4 indicators-LDH, CRP, CA 15-3, and CA 125-related to the prognosis in BC and established a prognostic model. The high LDH group showed worse overall survival (OS) than low LDH group (P = .017; hazard ratio (HR), 1.528; 95% confidence interval (CI), 1.055-2.215). The high CRP group showed worse OS than low CRP group (P = .004; HR, 1.666; 95% CI, 1.143-2.429). The high CA153 group showed worse OS than low CA 15-3 group (P=.011; HR, 1.563; 95% CI, 1.075-2.274). The high CA 125 group showed worse OS than low CA 125 group (P = .021; HR, 1.499; 95% CI, 1.031-2.181). The area under the curve for risk score was .824, Ki-67 was .628, age was .511, and grade was .545. Risk score was found to be an independent prognostic factor using multivariate Cox regression analysis. CONCLUSION: We successfully established an optimization model by combining 4 prognosis-related indicators to assess the prognosis in patients with metastatic BC.

Long Non-coding RNA RP11-395G23.3 Acts as a Competing Endogenous RNA of miR-124-3p to Regulate ROR1 in Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies with poor prognosis. However, the underlying mechanisms of ATC remain to be elucidated. Recently, increasing studies have focused on competitive endogenous RNA (ceRNA) to discover valuable biomarkers for the diagnosis of ATC. The present study identified 705 differentially expressed mRNAs and 47 differentially expressed lncRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. Additionally, an lncRNA/miRNA/mRNA network was constructed which included 1103 regulatory relations. The upregulation of RP11-395G23.3 in ATC cells was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In the loss of function assays, results suggested silencing of RP11-395G23.3 inhibited cell proliferation and induced cell apoptosis. Mechanically, RP11-395G23.3 could increase ROR1 via sponging miR-124-3p as a ceRNA. Moreover, ROR1 expression was decreased with the downregulation of RP11-395G23.3, but was rescued by the co-transfection of the miR-124-3p inhibitor in ATC cells. Our research suggested that the RP11-395G23.3/miR-124-3p/ROR1 axis potentially acted as a potential target for the diagnosis of ATC.

Effect of Warm Acupuncture Combined with Bone Marrow Mesenchymal Stem Cells Transplantation on Cartilage Tissue in Rabbit Knee Osteoarthritis.

The current study was designed to investigate the effect and underlying mechanism of warm acupuncture combined with bone marrow mesenchymal stem cells (BMSC) transplantation on cartilage tissue injury in rabbit knee osteoarthritis (KOA). In the study, 50 rabbits were randomly divided into 5 groups: blank group, KOA group, warm acupuncture group, BMSCs group, and warm acupuncture combined with BMSCs group. After warm acupuncture combined with BMSCs, the Modified Lequesne MG knee joint assessment scale was used to evaluate the degree of knee joint behavior, the Taiping Peng method generally observed the histomorphology changes of KOA rabbit cartilage, and hematoxylin-eosin staining, safranin O green staining, and toluidine blue staining were conducted to evaluate the extent of cartilage tissue pathology. Furthermore, transmission electron microscopy and TUNEL staining were used to observe cell apoptosis, and immunohistochemistry and qPCR analysis were used to detect the expression of apoptosis-related proteins and mRNA. Results showed that administration of warm acupuncture combined with BMSCs recovered the joint function and significantly decreased Lequesne MG score. The degree of cartilage tissue pathological damage has been improved, cartilage ultrastructure degeneration has recovered, peripheral blood vessels have mild edema, blood supply has gradually recovered, and even small amounts of red blood cells have appeared. In addition, warm acupuncture combined with BMSCs treatment suppressed chondrocyte apoptosis in rabbits with knee osteoarthritis by reduced TUNEL-positive chondrocytes and simultaneously reversed the mRNA expression of Bax, Bcl-2, and Caspase-3. These results indicate that warm acupuncture combined with BMSCs transplantation has a potential protective effect on rabbit KOA, which may be mediated by inhibiting chondrocyte apoptosis.

Assessing the prognostic value of stemness-related genes in breast cancer patients.

Breast cancer (BC) is currently one of the deadliest tumors worldwide. Cancer stem cells (CSCs) are a small group of tumor cells with self-renewal and differentiation abilities and high treatment resistance. One of the reasons for treatment failures is the inability to completely eliminate tumor stem cells. By using the edgeR package, we identified stemness-related differentially expressed genes in GSE69280. Via Lasso-penalized Cox regression analysis and univariate Cox regression analysis, survival genes were screened out to construct a prognostic model. Via nomograms and ROC curves, we verified the accuracy of the prognostic model. We selected 4 genes (PSMB9, CXCL13, NPR3, and CDKN2C) to establish a prognostic model from TCGA data and a validation model from GSE24450 data. We found that the low-risk score group had better OS than the high-risk score group, whether using TCGA or GSE24450 data. A prognostic model including four stemness-related genes was constructed in our study to determine targets of breast cancer stem cells (BCSCs) and improve the treatment effect.

Evaluation of a novel ultra-sensitive nanoparticle probe-based assay for ricin detection.

A gold nanoparticle (GNP) probe-based assay (GNPA) modified from the bio-barcode assay (BCA) was developed for ultrasensitive detection of ricin, a potential biothreat agent. In the GNPA, a chain of ricin was captured by a GNP probe coated with polyclonal antibodies and single-stranded signal DNA. A magnetic microparticle (MMP) probe coated with ricin A chain monoclonal antibody was then added to form an immuno-complex. After being magnetically separated, the immuno-complex containing the single-stranded signal DNA was characterized by PCR and real-time PCR. A detection limit of 10(-2) fg/ml was determined for the ricin A chain; this is eight orders of magnitude more sensitive than that achieved with an ELISA and two orders more sensitive than that obtained with the BCA. The coefficients of variation (CV) of the intra- and inter-assay values ranged from 3.82-6.46%. The results here show that this novel assay is an ultrasensitive method for detection of ricin proteins and may be suitable for the ultrasensitive detection of other proteins.

[Effects of supraorbital keyhole approach upon the clipping of distal basilar artery aneurysms].

OBJECTIVE: To explore the feasibility and efficacy of supraorbital keyhole approach (SOKA) for the clipping of distal basilar artery (BA) aneurysms. METHODS: A total of 12 patients with distal BA aneurysms were treated with SOKA. All patients had subarachnoid hemorrhage (SAH). They underwent surgeries for an average of 7.6 days post-SAH (n = 2, within 24 hours; n = 7, 3 - 14 days; n = 2, 2 week later). Aneurysms were located on BA (n = 10), posterior cerebral artery (PCA) 1-2 segment (n = 1) and PCA 2 segment (n = 1). One-stage operations were performed in 2 cases with BA bifurcation aneurysm accompanied with anterior cerebral artery (ACA) 1 segment aneurysm and multiple middle cerebral artery (MCA) aneurysms respectively. Anterior and posterior clinoid process was drilled off in 2 patients respectively to increase the room for maneuver. Posterior communicating artery was cut in one case to expand the working space. Once a balloon catheter was put into BA, proximal artery control was implemented if immature aneurysm rupture occurred. RESULTS: All distal BA aneurysms were completely clipped; 3 accompanied aneurysms were clipped together through single supraorbital keyhole approach. One aneurysm ruptured intra-operatively and was clipped successfully with temporary parent arterial occlusion. No conscious disturbance and dyskinesia occurred post-operatively for all patients. CONCLUSION: During the procedure of SOKA, anterior and posterior clinoidectomy may be applied to increase the working space. Distal BA aneurysms located less than 15 mm higher over anterior skull base can be effectively treated via SOKA.

[Preliminary application of keyhole approach for the treatment of posterior circulation aneurysms].

OBJECTIVE: To evaluate the feasibility and efficacy of minimally invasive keyhole approach for the treatment of posterior circulation aneurysms. METHODS: Twelve posterior circulation aneurysms were treated via the keyhole approach. Aneurysms were located in basilar artery (BA) in 6 patients (1 in BA bifurcation, 3 in BA-SCA [superior cerebellar artery], 1 in BA-PCA [posterior cerebral artery], 1 in PCA-BA-SCA), in PCA in 5 patients (1 in PCA1-2 segment, 2 PCA2 segment and 2 PCA2-3 segment) and in PICA [posterior inferior cerebellar artery] in 1 patient. The supraorbital keyhole approach was performed in 6 BA and 2 PCA1-2 segment aneurysms, the subtemporal approach in 3 PCA2-3 segment aneurysms and the lateral suboccipital keyhole approach in one PICA aneurysm. RESULTS: Among those 12 posterior circulation aneurysms, 9 aneurysms were completely clipped, 2 thrombotic PCA2-3 segment giant aneurysms trapped with thrombectomy, one gourd-shaped aneurysm in PICA incompletely clipped with no recurrent hemorrhage in during a 6-month follow-up. No intraoperative rupture of aneurysms occurred in any operation. All patients were discharged without neurological deficits. CONCLUSION: Anterior or posterior clinoid process may be drilled off under the keyhole approach to increase the manipulating space while clipping the posterior circulation aneurysms. Controlling the proximal parent artery by balloon catheter increases the operative safety. Neuronavigation is helpful in rapidly locating the distal PCA aneurysm. The individualized keyhole approaches can be applied feasible and effectively for the treatment of posterior circulation aneurysms.