Miracle-dz/UniFAR-FTUs huggingface dataset:
PdGNC confers drought tolerance by mediating stomatal closure resulted from NO and H2 O2 production via the direct regulation of PdHXK1 expression in Populus.

Drought is one of the primary abiotic stress, seriously implicate plant growth and productivity. Stomata play a crucial role in regulating drought tolerance. However, the molecular mechanism on stomatal movement-mediated drought tolerance remains unclear. Using genetic, molecular and biochemical techniques, we identified that the PdGNC directly activated the promoter of PdHXK1 by binding the GATC element, a hexokinase (HXK) synthesis key gene. Here, PdGNC, a member of the GATA transcription factor family, was greatly induced by ABA and dehydration. Overexpressing PdGNC in poplar (Populus clone 717) resulted in reduced stomatal aperture with greater water use efficiency (WUE) and increased water deficit tolerance. By contrast, CRISPR/Cas9-mediated poplar mutant gnc exhibited increased stomatal aperture and water loss with reducing drought resistance. PdGNC activates PdHXK1 (a hexokinase synthesis key gene), resulting in a remarkable increase in hexokinase activity in poplars subjected to water deficit. Furthermore, hexokinase promoted nitric oxide (NO) and hydrogen peroxide (H2 O2 ) production in guard cells, which ultimately reduced stomatal aperture and increased drought resistance. Together, PdGNC confers drought stress tolerance by reducing stomatal aperture caused by NO and H2 O2 production via the direct regulation of PdHXK1 expression in poplars.
Rare Variants in the DNA Repair Pathway and the Risk of Colorectal Cancer

Background: Inherited susceptibility is an important contributor to colorectal cancer risk, and rare variants in key genes or pathways could account in part for the missing proportion of colorectal cancer heritability. Methods: We conducted an exome-wide association study including 2,327 cases and 2,966 controls of European ancestry from three large epidemiologic studies. Single variant associations were tested using logistic regression models, adjusting for appropriate study-specific covariates. In addition, we examined the aggregate effects of rare coding variation at the gene and pathway levels using Bayesian model uncertainty techniques. Results: In an exome-wide gene-level analysis, we identified ST6GALNAC2 as the top associated gene based on the Bayesian risk index (BRI) method [summary Bayes factor (BF)BRI = 2604.23]. A rare coding variant in this gene, rs139401613, was the top associated variant (P = 1.01 × 10–6) in an exome-wide single variant analysis. Pathway-level association analyses based on the integrative BRI (iBRI) method found extreme evidence of association with the DNA repair pathway (BFiBRI = 17852.4), specifically with the nonhomologous end joining (BFiBRI = 437.95) and nucleotide excision repair (BFiBRI = 36.96) subpathways. The iBRI method also identified RPA2, PRKDC, ERCC5, and ERCC8 as the top associated DNA repair genes (summary BFiBRI ≥ 10), with rs28988897, rs8178232, rs141369732, and rs201642761 being the most likely associated variants in these genes, respectively. Conclusions: We identified novel variants and genes associated with colorectal cancer risk and provided additional evidence for a role of DNA repair in colorectal cancer tumorigenesis. Impact: This study provides new insights into the genetic predisposition to colorectal cancer, which has potential for translation into improved risk prediction.
Remote Hemodynamic‐Guided Therapy of Patients With Recurrent Heart Failure Following Cardiac Resynchronization Therapy

Background Patients with recurring heart failure (HF) following cardiac resynchronization therapy fare poorly. Their management is undecided. We tested remote hemodynamic‐guided pharmacotherapy. Methods and Results We evaluated cardiac resynchronization therapy subjects included in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Class III Heart Failure Patients) trial, which randomized patients with persistent New York Heart Association Class III symptoms and ≥1 HF hospitalization in the previous 12 months to remotely managed pulmonary artery (PA) pressure‐guided management (treatment) or usual HF care (control). Diuretics and/or vasodilators were adjusted conventionally in control and included remote PA pressure information in treatment. Annualized HF hospitalization rates, changes in PA pressures over time (analyzed by area under the curve), changes in medications, and quality of life (Minnesota Living with Heart Failure Questionnaire scores) were assessed. Patients who had cardiac resynchronization therapy (n=190, median implant duration 755 days) at enrollment had poor hemodynamic function (cardiac index 2.00±0.59 L/min per m2), high comorbidity burden (67% had secondary pulmonary hypertension, 61% had estimated glomerular filtration rate <60 mL/min per 1.73 m2), and poor Minnesota Living with Heart Failure Questionnaire scores (57±24). During 18 months randomized follow‐up, HF hospitalizations were 30% lower in treatment (n=91, 62 events, 0.46 events/patient‐year) versus control patients (n=99, 93 events, 0.68 events/patient‐year) (hazard ratio, 0.70; 95% CI, 0.51–0.96; P=0.028). Treatment patients had more medication up‐/down‐titrations (847 versus 346 in control, P<0.001), mean PA pressure reduction (area under the curve −413.2±123.5 versus 60.1±88.0 in control, P=0.002), and quality of life improvement (Minnesota Living with Heart Failure Questionnaire decreased −13.5±23 versus −4.9±24.8 in control, P=0.006). Conclusions Remote hemodynamic‐guided adjustment of medical therapies decreased PA pressures and the burden of HF symptoms and hospitalizations in patients with recurring Class III HF and hospitalizations, beyond the effect of cardiac resynchronization therapy. Registration URL: https://www.clinicaltrials. gov; Unique identifier: NCT00531661.
Quantitative Measurement of Plasma Free Metanephrines by a Simple and Cost-Effective Microextraction Packed Sorbent with Porous Graphitic Carbon and Liquid Chromatography-Tandem Mass Spectrometry

Plasma free metanephrines are widely used for the diagnosis of pheochromocytoma and paraganglioma (PPGL), yet quantifying metanephrines using a simple and cost-effective approach may be challenging due to preanalytical and analytical constraints. In this study, we established and validated a new method for quantitative measurement of plasma free metanephrines based on microextraction by packed sorbent (MEPS) with porous graphitic carbon (PGC) and liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The elution step was fully compatible with HILIC mode without evaporation and reconstitution. The analytes were well resolved, and potential interferences (54 substances) were investigated. This method was linear from 24.7–2717 pg/mL for metanephrine (MN) and 24.5–4010 pg/mL for normetanephrine (NMN) with a coefficient of determination (R2) higher than 0.994. The limit of MN and NMN detection were 12.4 pg/mL and 12.3 pg/mL, respectively. The intra- and interassay impressions were ≤12.8% for spiked quality controls and ≤13.6% for commercial quality controls; the method recoveries ranged within 88.0–109.0%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.848 ± 0.047 for MN and 0.979 ± 0.021 for NMN. Validation that was performed by comparing clinical specimens with various biochemical results showed that plasma free metanephrines in a seated position had comparable sensitivity and lower specificity to urinary free metanephrines, which could be compensated by combining other biochemical tests. The newly developed MEPS method resulted as a time-saving, reliable, and cost-effective microextraction technique that can be applied for a successful screening of PPGL.
Divergent and Linear Solid‐Phase Synthesis of PNA Containing Thiazole Orange as Artificial Base

Fluorescent nucleobase surrogates provide nucleic acids with interesting properties. We have recently introduced thiazole orange as base surrogate into PNA and found that the so-called FIT (Forced Intercalation of Thiazole orange) PNA probes signal hybridization by enhancements of fluorescence. Common approaches of modifying nucleobases or introducing nucleobase surrogates draw upon the usage of monomer building blocks that have been synthesized in solution phase. The need to prefabricate a base-modified building block can hold up progress if several base modifications or base surrogates are to be evaluated. Herein, a method for divergent solid-phase synthesis is presented that serves the purpose to facilitate the screening for base surrogates that fluoresce upon hybridization. An Fmoc/Aloc-protected submonomer allowed the application of commonly used Fmoc-based solid-phase synthesis protocols while removal of the fully orthogonal Aloc group enabled the on-resin introduction of base surrogates after the linear chain assembly had been completed. The divergent solid-phase synthesis strategy is automatable, gives overall yields matching those of linear solid-phase synthesis and, most importantly, provides rapid access to any kind of base-modified PNA. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Prevalence of Xanthomonas euvesicatoria (formally X. perforans) associated with bacterial spot severity in Capsicum annuum crops in South Central Chihuahua, Mexico

Background Xanthomonas spp. causes bacterial spot disease, which reduces quality and yield of pepper crops in Mexico. Identification of phytopathogen species is necessary to implement more effective control strategies. Objective The aim of this study was to isolate and identify infecting Xanthomonas species in South Central Chihuahua pepper-producing areas. Methods Diseased plants were collected from 30 cultivation lots and bacteria were isolated from damaged tissues. Potential causative agents were isolated, identified, and characterized by biochemical and molecular analysis. Pathogenicity tests from each isolate were then performed on 30-d-old pepper seedlings, exposing five leaves to 10 µL of 1 × 108 CFU/mL bacterial suspensions of each isolate, using sterile distilled water as a control. Disease severity was determined after 10 d by calculating leaf damage percentage. Furthermore, we evaluated the susceptibility of the highest bacterial spot severity-causing isolates (13 isolates) to copper sulphate (CuS), copper gluconate (CuG), copper oxychloride + oxytetracycline hydrochloride (Cu + Ox), gentamicin + oxytetracycline hydrochloride (Gen + Ox), and gentamicin sulphate (GenS). Copper-resistance genes (copLAB) were detected by PCR analysis among isolates. Results Thirty-seven foliage isolates were identified as Xanthomonas euvesicatoria (14%), which were associated with bacterial spot disease in jalapeño pepper. Tested Xanthomonas isolates were resistant to Cu-based compounds, but susceptible to Cu + Ox. All isolates were susceptible to Gen + Ox and GenS. CopLAB genes were detected in all but one strain. Conclusions X. euvesicatoria (formally X. perforans) may be considered as an emerging pathogen of bacterial spot pepper in Mexico. Among disease management strategies, alternatives to copper should be taken into consideration.
Complete mitochondrial genome of a predominant parasitoid, Necremnus tutae (Hymenoptera: Eulophidae) of the South American tomato leafminer Tuta absoluta (Lepidoptera: Gelechiidae)

Abstract The complete mitochondrial genome of a predominant parasitoid, Necremnus tutae (Hymenoptera: Eulophidae) (GenBank accession number MT916846) is 15,252 bp in length, and contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes, and an A + T-rich region. The overall base composition is 38.86% for A, 7.14% for C, 8.57% for G, and 45.43% for T, with a high AT bias of 84.29%. ATA, ATT, ATG were initiation codons and TAA and T were termination codons. All the 22 tRNAs displayed a typical cloverleaf secondary structure, except for trnS1 and trnR which lacked the dihydrouracil (DHU) arm. Phylogenetic analyses were performed using 13 PCGs showed that N. tutae is closely related to Tenthredo tienmushana, which in accordance with the traditional classification.
Clinical outcomes of proximal gastrectomy for gastric cancer: A comparison between the double-flap technique and jejunal interposition

Background The optimal reconstruction method after proximal gastrectomy (PG) has been debatable. Recent reports have shown that the double-flap technique (DFT) provides good outcomes in terms of postoperative nutritional status and quality of life. However, no study has compared the clinical outcomes of the DFT with other reconstruction methods. Here, we evaluated and compared the clinical outcomes between the DFT and jejunal interposition (JI) after PG for gastric cancer. Materials and methods The medical records of 34 consecutive patients who had undergone PG for upper third gastric cancer between January 2011 and October 2016 were reviewed retrospectively. The main factors investigated were surgical outcomes, postoperative nutritional status, symptoms, and endoscopic findings 1 year after surgery. Results Thirty-four patients were enrolled (DFT, 14; JI, 20). The operation time was similar between the two techniques (228 and 246 minutes for DFT and JI, respectively, P = 0.377), as were the rates of anastomotic complications (7% and 0% for DFT and JI, respectively, P = 0.412). Body weight loss was significantly lower in the DFT group than in the JI group (-8.1% vs -16.1%, P = 0.001). Total protein and albumin levels were higher in the DFT group than in the JI group (0% vs -2.9%, P = 0.053, and -0.3% vs -6.1%, P = 0.077, respectively). One patient in the DFT group and no patients in the JI group experienced reflux esophagitis (≥ grade B) (P = 0.393). Anastomotic strictures were not observed as postoperative complications in either group. Conclusions Surgical outcomes revealed that the DFT was safe and feasible, similar to JI. In terms of controlling postoperative body weight loss, the DFT is a better reconstruction technique than JI after PG.
Prediction of Recurrence in Patients with Stage III Colon Cancer Using Conventional Clinicopathological Factors and Peripheral Blood Test Data: A New Analysis with Artificial Intelligence

Background: Survival rate may be predicted by tumor-node-metastasis staging systems in colon cancer. In clinical practice, about 20 to 30 clinicopathological factors and blood test data have been used. Various predictive factors for recurrence have been advocated; however, the interactions are complex and remain to be established. We used artificial intelligence (AI) to examine predictive factors related to recurrence. Methods: The study group comprised 217 patients who underwent curative surgery for stage III colon cancer. Using a self-organizing map (SOM), an AI-based method, patients with only 23 clinicopathological factors, patients with 23 clinicopathological factors and 34 of preoperative blood test data (pre-data), and those with 23 clinicopathological factors and 31 of postoperative blood test data (post-data) were classified into several clusters with various rates of recurrence. Results: When only clinicopathological factors were used, the percentage of T4b disease, the percentage of N2 disease, and the number of metastatic lymph nodes were significantly higher in a cluster with a higher rate of recurrence. When clinicopathological factors and pre-data were used, three described pathological factors and the serum C-reactive protein (CRP) levels were significantly higher and the serum total protein (TP) levels, serum albumin levels, and the percentage of lymphocytes were significantly lower in a cluster with a higher rate of recurrence. When clinicopathological factors and post-data were used, three described pathological factors, serum CRP levels, and serum carcinoembryonic antigen levels were significantly higher and serum TP levels, serum albumin levels, and the percentage of lymphocytes were significantly lower in a cluster with a higher rate of recurrence. Conclusions: This AI-based analysis extracted several risk factors for recurrence from more than 50 pathological and blood test factors before and after surgery separately. This analysis may predict the risk of recurrence of a new patient by confirming which clusters this patient belongs to.
Differential Pathogenesis between Andes Virus Strains CHI-7913 and Chile-9717869 in Syrian Hamsters

Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS; also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease. ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory disease caused by orthohantaviruses in the Americas with a fatality rate as high as 35%. In South America, Andes orthohantavirus (Hantaviridae, Orthohantavirus; ANDV) is a major cause of HCPS, particularly in Chile and Argentina, where thousands of cases have been reported since the virus was discovered. Two strains of ANDV that are classically used for experimental studies of the virus are Chile-9717869, isolated from the natural reservoir, the long-tailed pygmy rice rat, and CHI-7913, an isolate from a lethal human case of HCPS. An important animal model for studying pathogenesis of HCPS is the lethal Syrian golden hamster model of ANDV infection. In this model, ANDV strain Chile-9717869 is uniformly lethal and has been used extensively for pathogenesis, vaccination, and therapeutic studies. Here, we show that the CHI-7913 strain, despite having high sequence similarity with Chile-9717869, does not cause lethal disease in Syrian hamsters. CHI-7913, while being able to infect hamsters and replicate to moderate levels, showed a reduced ability to replicate within the tissues compared with Chile-9717869. Hamsters infected with CHI-7913 had reduced expression of cytokines interleukin-4 (IL-4), IL-6, and gamma interferon compared with Chile-9717869-infected animals, suggesting potentially limited immune-mediated pathology. These results demonstrate that certain ANDV strains may not be lethal in the classical Syrian hamster model of infection, and further exploration into the differences between lethal and nonlethal strains should provide important insights into molecular determinants of pathogenic hantavirus infection. IMPORTANCE Andes orthohantavirus (ANDV) is a New World hantavirus that is a major cause of hantavirus cardiopulmonary syndrome (HCPS; also referred to as hantavirus pulmonary syndrome) in South America, particularly in Chile and Argentina. ANDV is one of the few hantaviruses for which there is a reliable animal model, the Syrian hamster model, which recapitulates important aspects of human disease. Here, we infected hamsters with a human isolate of ANDV, CHI-7913, to assess its pathogenicity compared with the classical lethal Chile-9717869 strain. CHI-7913 had 22 amino acid differences from Chile-9717869, did not cause lethal disease in hamsters, and showed reduced ability to replicate in vivo. Our data indicate potentially important molecular signatures for the pathogenesis of ANDV infection in hamsters and may lead to insights into what drives the pathogenesis of certain hantaviruses in humans.
Comparison of Physiological Parameters During On-Water and Ergometer Kayaking and Their Relationship to Performance in Sprint Kayak Competitions.

PURPOSE (1) To compare various physiological indicators of performance during a 5 × 1500-m incremental kayak test performed on an ergometer and on-water and (2) to analyze the relationships between these indicators and the actual competition performance of elite sprint kayakers, aiming to provide information to coaches for evaluating and planning training on-water. METHODS A total of 14 male and female German elite sprint kayakers performed an incremental test both on an ergometer and on-water. The tissue saturation index of the musculus (m.) biceps brachii, oxygen consumption, ratings of perceived exertion, and levels of blood lactate were measured and compared with actual racing times. In addition, power output was monitored during ergometer testing only. RESULTS Oxygen consumption during the fourth (P = .02; d = 0.32) and final (fifth; P < .001; d = 0.32) steps of incremental testing was higher on-water than on the ergometer. The tissue saturation index of the m. biceps brachii was approximately 21% higher at the end of the ergometer test (P = .002; d = 1.14). During the second (P = .01; d = 0.78), third (P = .005; d = 0.93), and fourth stages (P = .005; d = 1.02), the ratings of perceived exertion for ergometer kayaking was higher. During the final step, power output was most closely correlated to 200- (r = .88), 500- (r = .93), and 1000-m (r = .86) racing times (all Ps < .01). CONCLUSIONS During high-intensity kayaking on an ergometer or on-water, the oxygen consumption and tissue saturation index of the m. biceps brachii differ. Furthermore, at moderate to submaximal intensities, the ratings of perceived exertion were higher for ergometer than for on-water kayaking. Finally, of all parameters assessed, the power output during ergometer kayaking exhibited the strongest correlation with actual racing performance.
Exosomes in Breast Cancer – Mechanisms of Action and Clinical Potential

Extracellular vesicles (EV) are a heterogeneous group of cell-derived membrane vesicles comprising apoptotic bodies, microvesicles, and small EVs also called as exosomes. Exosomes when initially identified were considered as a waste product but the advancement in research techniques have provided insight into the important roles of exosomes in cell–cell communication, various biological processes and diseases, including cancer. As an important component of EVs, exosomes contain various biomolecules such as miRNAs, lipids, and proteins that largely reflect the characteristics of their parent cells. Notably, cancer cells generate and secrete many more exosomes than normal cells. A growing body of evidence suggests that exosomes, as mediators of intercellular cross-talk, play a role in tumorigenesis, cancer cell invasion, angiogenesis, tumor microenvironment (TME) formation, and cancer metastasis. As we gain more insights into the association between exosomes and cancer, the potential of exosomes for clinical use is becoming more intriguing. This review is focused on the role of exosomes in breast cancer, in terms of breast cancer biology, mechanism of action, potential as biomarkers, and therapeutic opportunities.