BackgroundHow plants respond to dehydration stress has been extensively researched. However, how plants respond to multiple consecutive stresses is virtually unknown. Pre-exposure to various abiotic stresses (including dehydration) may alter plants’ subsequent responses by improving resistance to future exposures. These observations have led to the concept of ‘stress memory’ implying that during subsequent exposures plants provide responses that are different from those during their first encounter with the stress. Genes that provide altered responses in a subsequent stress define the ‘memory genes’ category; genes responding similarly to each stress form the ‘non-memory’ category.ResultsUsing a genome-wide RNA-Seq approach we determine the transcriptional responses of Arabidopsis plants that have experienced multiple exposures to dehydration stress and compare them with the transcriptional behavior of plants encountering the stress for the first time. The major contribution of this study is the revealed existence of four distinct, previously unknown, transcription memory response patterns of dehydration stress genes in A.thaliana. The biological relevance for each of the four memory types is considered in the context of four overlapping strategies employed by a plant to improve its stress tolerance and/or survival: 1) increased synthesis of protective, damage-repairing, and detoxifying functions; 2) coordinating photosynthesis and growth under repetitive stress; 3) re-adjusting osmotic and ionic equilibrium to maintain homeostasis; and 4) re-adjusting interactions between dehydration and other stress/hormone regulated pathways.ConclusionsThe results reveal the unknown, hitherto, existence of four distinct transcription memory response types in a plant and provide genome-wide characterization of memory and non-memory dehydration stress response genes in A.thaliana. The transcriptional responses during repeated exposures to stress are different from known responses occurring during a single exposure. GO analyses of encoded proteins suggested implications for the cellular/organismal protective, adaptive, and survival functions encoded by the memory genes. The results add a new dimension to our understanding of plants’ responses to dehydration stress and to current models for interactions between different signaling systems when adjusting to repeated spells of water deficits.
SummaryInvestigations into the role of tomato ARF6 and ARF8 reveal that they are critical components in floral and gynoecium development before anthesis.
IMPORTANCE Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH.OBJECTIVE To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. DESIGN, SETTING, AND PARTICIPANTSThe Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified.INTERVENTIONS Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week.RESULTS One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported.CONCLUSIONS AND RELEVANCE Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH.
The PNI is a simple and useful marker not only to identify patients at increased risk for postoperative complications, but also to predict long-term survival after total gastrectomy. The PNI should be included in the routine assessment of advanced gastric cancer patients.
Background: Intestinal microbiota plays an important role in regulating metabolism, physiology, and immune response of the host. L-Tryptophan (Trp) are metabolized by several genera of bacteria. It remains largely unknown whether Trp can regulate the composition and diversity of the intestinal microbiota and contribute to intestinal homeostasis.Methods: A total of 126 weaning piglets were fed a corn- and soybean meal-based diet supplemented with 0, 0.2, or 0.4% Trp for 4 weeks. The intestinal microbiota was measured by using bacterial 16S rRNA gene-based high-throughput sequencing methods. Metabolites of Trp and short-chain fatty acids (SCFAs) in the hindgut were determined by high-performance liquid chromatography and gas chromatography, respectively. The mRNA levels for aromatic hydrocarbon receptor (AhR), tumor necrotic factor-α (TNF-α), interleukin-8 (IL-8), and protein abundances of tight junction proteins were determined.Results: Compared with the control group, Trp supplementation enhanced piglet growth performance and markedly altered the intestinal microbial composition as evidenced by enhanced alpha and beta diversity in the microbiome (P < 0.05). The abundances of Prevotella, Roseburia, and Succinivibrio genera were enriched, but those of Clostridium sensu stricto and Clostridium XI, opportunistic pathogens, were decreased with dietary Trp supplementation. Analysis of metabolic pathways indicated enhanced indole alkaloid biosynthesis and Trp metabolism, which was validated by elevated concentrations of 3-indoleacetic acid and indole in the intestinal contents of Trp-supplemented piglets (P < 0.05). These changes in Trp metabolites were correlated with activation of AhR and cytochrome p4501 A1 (CYP1A1) in cecum and colonic tissues, and with a decrease in the intestinal mucosal IL-8 mRNA level. Moreover, the protein abundances for zonula occluden (ZO)-1 and occludin were upregulated by Trp supplementation in colonic tissues.Conclusion: Dietary Trp supplementation altered intestinal microbial composition and diversity, improved intestinal mucosal barrier function, activated AhR signaling, and downregulated expression of inflammatory cytokines in the large intestine of weaned piglets. These results indicate a crosstalk between dietary Trp and intestine in nutrition, microbial metabolism, and mucosal immunity.
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