Split application of polymer-coated urea combined with common urea improved nitrogen efficiency without sacrificing wheat yield and benefits while saving 20% nitrogen input.

Controlled-release nitrogen fertilizer (CRNF) has been expected to save labor input, reduce environmental pollution, and increase yield in crop production. However, the economic feasibility is still controversial due to its high cost. To clarify the suitable application strategy of CRNF in promoting the yield, nitrogen use efficiency and income on wheat grown in paddy soil, four equal N patterns were designed in 2017-2021 with polymer-coated urea (PCU) and common urea as material, including PCU applied once pre-sowing (M1), PCU applied 60% at pre-sowing and 40% at re-greening (M2), 30% PCU and 30% urea applied at pre-sowing, 20% PCU and 20% urea applied at re-greening (M3), and urea applied at four stage (CK, Basal:tillering:jointing:booting=50%:10%:20%:20%). In addition, M4-M6, which reduced N by 10%, 20% and 30% respectively based on M3, were designed in 2019-2021 to explore their potential for N-saving and efficiency-improving. The results showed that, compared with CK, M1 did not significantly reduce yield, but decreased the average N recovery efficiency (NRE) and benefits by 1.63% and 357.71 CNY ha-1 in the four years, respectively. M2 and M3 promoted tiller-earing, delayed the decrease of leaf area index (LAI) at milk-ripening stage, and increased dry matter accumulation post-anthesis, thereby jointly increasing spike number and grain weight of wheat, which significantly increased yield and NRE compared with CK in 2017-2021. Due to the savings in N fertilizer costs, M3 achieved the highest economic benefits. With the 20% N reduction, M5 increased NRE by 16.95% on average while decreasing yield and net benefit by only 6.39% and 7.40% respectively, compared with M3. Although NRE could continue to increase, but the yield and benefits rapidly decreased after N reduction exceeds 20%. These results demonstrate that twice-split application of PCU combined with urea is conducive to achieving a joint increase in yield, NRE, and benefits. More importantly, it can also significantly improve the NRE without losing yield and benefits while saving 20% N input.

Survival benefit of surgery for second primary esophageal cancer following gastrointestinal cancer: a population-based study.

BACKGROUND: The incidence of second primary malignancy is increasing. However, although there is some information on second primary esophageal cancer (SPEC) itself, there is no study or guideline on the use of surgery for SPEC after gastrointestinal cancer (SPEC-GC). Thus, this study aimed to gather evidence for the benefits of surgery by analyzing a national cohort and determining the prognostic factors and clinical treatment decisions for SPEC-GC. METHODS: Data for patients with SPEC-GC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The prognostic factors of SPEC-GC were investigated by stepwise Cox proportional hazards regression and Kaplan-Meier analyses for overall survival and cancer-specific survival. RESULTS: A total of 8308 patients with SPEC were selected, including 582 patients with SPEC-GC. Multivariate analysis revealed that surgery, year of diagnosis, scope of regional lymph node surgery, tumor differentiation grade, SEER historic stage, and triple therapy were significant predictors of survival outcomes (P < .05). Surgery seemed to improve the prognosis of patients with SPEC-GC significantly compared with no surgery and chemoradiotherapy (P < .001). CONCLUSIONS: Surgery should be considered as the main treatment for SPEC-GC. Surgery, year of diagnosis, scope of regional lymph node surgery, tumor differentiation grade, SEER historic stage, and triple therapy were found to be independent prognostic factors for these patients. These factors should be considered in the clinical diagnosis and treatment of SPEC-GC.

The fate of nitrogen from different sources in a rice-wheat rotation system - A 15N labeling study.

High loss and low nitrogen (N) efficiency in agricultural production is severe. Also, ammonia volatilization and N leaching aggravated environmental pollution. The eutrophication of surface water and the emissions of N2O increased, hence green fertilization management urgently needs to be rationalized. Coordinating N supply from different sources has been shown to reduce environmental pollution. Therefore, this study was dedicated to clarifying the transport of N sources in the rice-wheat rotation system. The stable isotope tracer technology was used to label fertilizer (F), soil (T), and straw (J) with 15N, respectively. The utilization of N by crops (the N ratio in organs), as well as the residual N in soil and loss status, were measured. According to the potential of response to N, all the wheat cultivars were divided into groups with high (HNV) and low efficiency (LNV). The N contribution ratio showed that 43.28%~45.70% of total N accumulation was from T, while 30.11%~41.73% and 13.82%~24.19% came from F and J. The trend in soil N residue (T > F > J) was consistent with the above, while it was the opposite in N loss (T< F< J). The seasonal effectiveness showed that T achieved the highest N utilization efficiency (31.83%~44.69%), followed by F (21.05%~39.18%) and J (11.02%~16.91%). The post-season sustainability showed that T decreased the most in soil N residue (2.08%~12.53%), and F decreased the most in N accumulation (9.64%~18.13%). However, J showed an increase in N recovery rate (2.87%~5.89%). N translocation and distribution showed that N from different sources in grains was significantly higher than that in stems, glumes, and leaves. The ratio of HNV (75.14%~79.62%) was higher than that of LNV (71.90%~74.59%) in grain, while it was the opposite in other organs. Plant N accumulation, soil N supply, and straw N transformation were determined jointly by the three N sources, thus reducing N loss and N2O production. Therefore, the results will highlight the insights for constructing local N and emission reduction models.

Alcohol drinking alters oral microbiota to modulate the progression of alcohol-related liver disease.

Alcohol-related liver disease (ALD) is one of the leading causes of liver-related death worldwide. However, roles of oral microbiota in regulating the progression of ALD remain unknown. Here, we fed mice with control or ethanol diet to establish chronic-plus-binge ALD model. 16S ribosomal DNA sequencing was performed on oral and cecum samples. We demonstrated that alcohol drinking influenced bacterial richness, microbial structure, and composition in oral samples of ethanol-fed mice compared with control mice. Alcohol consumption also remodeled relationships among oral microbes and altered functions of oral microbiota. Furthermore, oral microbiota, such as Streptococcus, Helicobacter, Alloprevotella, and Psychrobacter were closely associated with ALD parameters. Finally, we observed Sutterellaceae_uncultured, Dyella, and Gemmatimonas possibly translocated along with oral-gut axis and positively correlated with the severity of ALD. Altogether, alcohol consumption reprogramed composition and functions of oral microbiota to promote ALD progression, suggesting that oral microbes might become a new target for ALD therapy.

Amlodipine, an anti-hypertensive drug, alleviates non-alcoholic fatty liver disease by modulating gut microbiota.

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) represents a severe public health problem. It often coexists with hypertension in the context of metabolic syndrome. We investigated the effects of amlodipine on NAFLD combined with hypertension and investigated the underlying mechanism/s. EXPERIMENTAL APPROACH: Mice were fed with high-fat diet (HFD) and 0.05% N-nitro-L-arginine methylester sterile water to induce NAFLD with hypertension. Gut microbiota composition and function were assessed by 16S ribosomal DNA and metagenomic sequencing. Untargeted metabolome profiles were applied to identify differential metabolites in mice caecum. KEY RESULTS: Amlodipine besylate and amlodipine aspartate significantly decreased liver injury and hepatic steatosis, and improved lipid metabolism with a concomitant reduction in the expression of lipogenic genes in mice with NAFLD and hypertension. Mechanistically, amlodipine besylate and amlodipine aspartate have potential to restore intestinal barrier integrity and improve antimicrobial defence, along with the elevated abundances of Akkermansia, Bacteroides and Lactobacillus. Noteworthily, the gut microbiota in amlodipine besylate- and amlodipine aspartate-treated mice had higher abundance of functional genes involved in taurine and hypotaurine metabolism. Consistently, the strengthened taurine and hypotaurine metabolism was confirmed by untargeted metabolome analysis. Based on the correlation and causal analysis, the altered gut microbiota composition and the enhancement of taurine and hypotaurine metabolism may synergistically decreased alanine aminotransferase, liver triglycerides, lipogenic genes and plasma cholesterol in HFD-fed hypertensive mice. CONCLUSION AND IMPLICATIONS: Amlodipine besylate and amlodipine aspartate exert multifactorial improvements in NAFLD and hypertension by modulating gut microbiota. They may serve as promising therapeutic agents for treating these diseases.

Aryl Hydrocarbon Receptor Deficiency in Intestinal Epithelial Cells Aggravates Alcohol-Related Liver Disease.

BACKGROUND & AIMS: The ligand-activated transcription factor, aryl hydrocarbon receptor (AHR) can sense xenobiotics, dietary, microbial, and metabolic cues. Roles of Ahr in intestinal epithelial cells (IECs) have been much less elucidated compared with those in intestinal innate immune cells. Here, we explored whether the IEC intrinsic Ahr could modulate the development of alcohol-related liver disease (ALD) via the gut-liver axis. METHODS: Mice with IEC specific Ahr deficiency (AhrΔIEC) were generated and fed with a control or ethanol diet. Alterations of intestinal microbiota and metabolites were investigated by 16S ribosomal RNA sequencing, metagenomics, and untargeted metabolomics. AHR agonists were used to evaluate the therapeutic potentials of intestinal Ahr activation for ALD treatment. RESULTS: AhrΔIEC mice showed more severe liver injury after ethanol feeding than control mice. Ahr deficiency in IECs altered the intestinal metabolite composition, creating an environment that promoted the overgrowth of Helicobacter hepaticus and Helicobacter ganmani in the gut, enhancing their translocation to mesenteric lymph nodes and liver. Among the altered metabolites, isobutyric acid was increased in the cecum of ethanol-fed AhrΔIEC mice relative to control mice. Furthermore, both H.hepaticus and isobutyric acid administration aggravated ethanol-induced liver injury in vivo and in vitro. Supplementation with AHR agonists, 6-formylindolo[3,2-b]carbazole and indole-3-carbinol, protected mice from ALD development by specifically activating intestinal Ahr without affecting liver Ahr function. Alcoholic patients showed lower intestinal AHR expression and higher H.hepaticus levels compared with healthy individuals. CONCLUSIONS: Our results indicate that targeted restoration of IEC intrinsic Ahr function may present as a novel approach for ALD treatment.

GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms.

GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.