SUMMARY
Although the biochemical and genetic basis of lipid metabolism is clear in Arabidopsis, there is limited information concerning the relevant genes in Glycine max (soybean). To address this ...issue, we constructed three‐dimensional genetic networks using six seed oil‐related traits, 52 lipid metabolism‐related metabolites and 54 294 SNPs in 286 soybean accessions in total. As a result, 284 and 279 candidate genes were found to be significantly associated with seed oil‐related traits and metabolites by phenotypic and metabolic genome‐wide association studies and multi‐omics analyses, respectively. Using minimax concave penalty (MCP) and smoothly clipped absolute deviation (SCAD) analyses, six seed oil‐related traits were found to be significantly related to 31 metabolites. Among the above candidate genes, 36 genes were found to be associated with oil synthesis (27 genes), amino acid synthesis (four genes) and the tricarboxylic acid (TCA) cycle (five genes), and four genes (GmFATB1a, GmPDAT, GmPLDα1 and GmDAGAT1) are already known to be related to oil synthesis. Using this information, 133 three‐dimensional genetic networks were constructed, 24 of which are known, e.g. pyruvate–GmPDAT–GmFATA2–oil content. Using these networks, GmPDAT, GmAGT and GmACP4 reveal the genetic relationships between pyruvate and the three major nutrients, and GmPDAT, GmZF351 and GmPgs1 reveal the genetic relationships between amino acids and seed oil content. In addition, GmCds1, along with average temperature in July and the rainfall from June to September, influence seed oil content across years. This study provides a new approach for the construction of three‐dimensional genetic networks and reveals new information for soybean seed oil improvement and the identification of gene function.
Significance Statement
One hundred and thirty‐three three‐dimensional genetic networks among seed oil‐related traits, lipid metabolism‐related metabolites and genes in soybean were constructed for the first time using phenotypic and metabolic genome‐wide association studies and multi‐omics analyses. These networks were used to try to explain the genetic relationships among seed oil‐related traits, oil synthesis‐related carbon metabolites and oil synthesis‐related amino acids.
Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships ...between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD).
Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity.
A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species,
and
, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic
decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats.
Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients.
This study was registered at ClinicalTrials.gov (NCT03010696).
Background and Aim
Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury ...and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality.
Methods
This was a two‐phase double‐blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness.
Results
In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005).
Conclusions
The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).
Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting ...stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery.
Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days.
Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 1.8% of 857 patients) than in the general anesthesia group (43 5.0% of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 49% vs. 288 33%; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 58% vs. 387 45%; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001).
Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.
Salt stress significantly reduces soybean yield. To improve salt tolerance in soybean, it is important to mine the genes associated with salt tolerance traits.
Salt tolerance traits of 286 soybean ...accessions were measured four times between 2009 and 2015. The results were associated with 740,754 single nucleotide polymorphisms (SNPs) to identify quantitative trait nucleotides (QTNs) and QTN-by-environment interactions (QEIs) using three-variance-component multi-locus random-SNP-effect mixed linear model (3VmrMLM). As a result, eight salt tolerance genes (GmCHX1, GsPRX9, Gm5PTase8, GmWRKY, GmCHX20a, GmNHX1, GmSK1, and GmLEA2-1) near 179 significant and 79 suggested QTNs and two salt tolerance genes (GmWRKY49 and GmSK1) near 45 significant and 14 suggested QEIs were associated with salt tolerance index traits in previous studies. Six candidate genes and three gene-by-environment interactions (GEIs) were predicted to be associated with these index traits. Analysis of four salt tolerance related traits under control and salt treatments revealed six genes associated with salt tolerance (GmHDA13, GmPHO1, GmERF5, GmNAC06, GmbZIP132, and GmHsp90s) around 166 QEIs were verified in previous studies. Five candidate GEIs were confirmed to be associated with salt stress by at least one haplotype analysis. The elite molecular modules of seven candidate genes with selection signs were extracted from wild soybean, and these genes could be applied to soybean molecular breeding. Two of these genes, Glyma06g04840 and Glyma07g18150, were confirmed by qRT-PCR and are expected to be key players in responding to salt stress.
Around the QTNs and QEIs identified in this study, 16 known genes, 6 candidate genes, and 8 candidate GEIs were found to be associated with soybean salt tolerance, of which Glyma07g18150 was further confirmed by qRT-PCR.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Purpose
The cytokine activin C is mainly expressed in small‐diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of activin C in ...neuropathic pain remain elusive.
Experimental Approach
Male rats and wild‐type and TRPV1 knockout mice with peripheral nerve injury ‐ sciatic nerve axotomy and spinal nerve ligation in rats; chronic constriction injury (CCI) in mice – provided models of chronic neuropathic pain. Ipsilateral lumbar (L)4–5 DRGs were assayed for activin C expression. Chronic neuropathic pain animals were treated with intrathecal or locally pre‐administered activin C or the vehicle. Nociceptive behaviours and pain‐related markers in L4–5 DRGs and spinal cord were evaluated. TRPV1 channel modulation by activin C was measured.
Key Results
Following peripheral nerve injury, expression of activin βC subunit mRNA and activin C protein was markedly up‐regulated in L4–5 DRGs of animals with axotomy, SNL or CCI. Correction added on 26 November 2020, after first online publication: The preceding sentence has been corrected in this current version. Intrathecal activin C dose‐dependently inhibited neuropathic pain in spinal nerve ligated rats. Local pre‐administration of activin C decreased neuropathic pain, macrophage infiltration into ipsilateral L4–5 DRGs and microglial reaction in L4–5 spinal cords of mice with CCI. In rat DRG neurons, activin C enhanced capsaicin‐induced TRPV1 currents. Pre‐treatment with activin C reduced capsaicin‐evoked acute hyperalgesia and normalized capsaicin‐evoked persistent hypothermia in mice. Finally, the analgesic effect of activin C was abolished in TRPV1 knockout mice with CCI.
Conclusion and Implications
Activin C inhibits neuropathic pain by modulating TRPV1 channels, revealing potential analgesic applications in chronic neuropathic pain therapy.
Background and Aims
Add‐on devices have been widely used in clinical practice. The aim of this meta‐analysis was to compare the adenoma detection rate between Endocuff‐assisted colonoscopy (EAC) and ...cap‐assisted colonoscopy (CAC).
Methods
PubMed, EMBASE, SCOPUS, and Cochrane databases were searched. Outcomes included adenoma detection rate, cecal intubation rate, cecal intubation time, and withdrawal time. Dichotomous data were pooled to obtain the odds ratio or risk ratio. Continuous data were pooled using the mean difference.
Results
Of the 240 articles reviewed, six randomized controlled trials were included, with a total of 1994 patients. In the meta‐analysis, no statistical difference in adenoma detection rate was detected between EAC and CAC (47.0% vs 45.1%; P = 0.33). EAC significantly improved detection rate of diminutive adenomas/polyps compared with CAC (P = 0.01). Cecal intubation was achieved in 96.5% in EAC group and 97.9% in CAC group (P = 0.04). Besides, no statistical difference was found in cecal intubation time (P = 0.86), withdrawal time (P = 0.88), small adenomas/polyps (P = 0.60), or large adenomas/polyps (P = 0.95).
Conclusion
EAC and CAC have their respective merits. EAC significantly improve the detection of diminutive adenomas/polyps. CAC was better in cecal intubation rate.
To preliminary evaluate the application of SaCoVLM™ video laryngeal mask airway in airway management of general anesthesia.
We recruited 100 adult patients (ages 18-78 years, male 19, female 81, ...weight 48-90 kg) with normal predicted airway (Mallampati I ~ II, unrestricted mouth opening, normal head and neck mobility) and ASA I-II who required general anaesthesia. The SaCoVLM™ was inserted after anesthesia induction and connected with the anesthesia machine for ventilation. Our primary outcome was glottic visualization grades. Secondary outcomes included seal pressure, success rate of insertion, intraoperative findings (gastric reflux and contraposition), gastric drainage and 24-h complications after operation.
The laryngeal inlet was exposed in all the patients and shown on the video after SaCoVLM™ insertion. The status of glottic visualization was classified: grade 1 in 55 cases, grade 2 in 23 cases, grade 3 in 14 cases and grade 4 in 8 cases. The first-time success rate of SaCoVLM™ insertion was 95% (95% CI = 0.887 to 0.984), and the total success rate was 96% (95% CI = 0.901 to 0.989). The sealing pressure of SaCoVLM™ was 34.1 ± 6.2 cmH
O and the gastric drainage were smooth. Only a small number of patients developed mild complications after SaCoVLM™ was removed (such as blood stains on SaCoVLM™ and sore throat).
The SaCoVLM™ can visualize partial or whole laryngeal inlets during the surgery, with a high success rate, a high sealing pressure and smooth gastroesophageal drainage. SaCoVLM™ could be a promise new effective supraglottic device to airway management during general anesthesia.
ChiCTR, ChiCTR2000028802 .Registered 4 January 2020.
Background and Aim
The effect of real‐time analysis of needle‐based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed ...to investigate the diagnostic efficacy of real‐time nCLE for gastric SELs and to assess the technical aspects and safety of real‐time nCLE.
Methods
Consecutive patients with gastric SELs ≥ 1 cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS‐nCLE, real‐time nCLE diagnosis was made by an expert endoscopist. The procedure‐relative adverse events were assessed and recorded. One‐month washout period later, nCLE videos were reviewed off‐line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists.
Results
Except for one failing to be punctured, 60 patients completed EUS‐nCLE procedures successfully. Real‐time nCLE had high diagnostic accuracies of ≥ 88.3% for gastric SELs. There were no significant differences between real‐time and off‐line nCLE diagnoses for gastric SELs (P > 0.05). The overall accuracy of real‐time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure‐relative adverse events occurred. In addition, the mean image quality score was 3.6 (1 = poor and 5 = excellent). The interobserver agreement was “almost perfect” for ectopic pancreas and “substantial” for gastrointestinal stromal tumor, leiomyoma, and carcinoma.
Conclusions
Endoscopic ultrasound‐nCLE could provide in vivo real‐time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real‐time nCLE was feasible and had a satisfactory safety profile.
Background:
Microbial dysbiosis is closely associated with visceral hypersensitivity and is involved in the pathogenesis of irritable bowel syndrome (IBS), but the specific strains that play a key ...role have yet to be identified. Previous bioinformatic studies have demonstrated that
Fusobacterium
is a shared microbial feature between IBS patients and maternal separation (MS)-stressed rats. In this study, we assessed the potential role of
Fusobacterium nucleatum
(
F. nucleatum
) in the pathogenesis of IBS.
Methods:
Fecal samples of patients with diarrhea predominant-IBS (IBS-D) and healthy controls were obtained. An MS rat model was established to receive gavage of either
F. nucleatum
or normal saline. Visceral sensitivity was evaluated through colorectal distension test, and fecal microbiota was analyzed by 16S rRNA gene sequencing.
F. nucleatum
-specific IgA levels in fecal supernatants were assessed by western blotting. The antigen reacted with the specific IgA of
F. nucleatum
was identified by mass spectrometry and the construction of a recombinant
Escherichia coli
BL21 (DE3).
Results:
IBS-D patients showed a lower Shannon index and a higher abundance of
Fusobacterium
. The
F. nucleatum
-gavage was shown to exacerbate visceral hypersensitivity in MS rats, with both the
F. nucleatum
-gavage and MS causing a decreased Shannon index and a clear segregation of fecal microbiota. In addition, specific IgA against
F. nucleatum
was detected in fecal supernatants of both the
F. nucleatum
-gavaged rats and the IBS-D patients. The FomA protein, which is a major outer membrane protein of
F. nucleatum
, was confirmed to react with the specific IgA of
F. nucleatum
in fecal supernatants.
Conclusion:
Fusobacterium
increased significantly in IBS-D patients, and
F. nucleatum
was involved in the pathogenesis of IBS by causing microbial dysbiosis and exacerbating visceral hypersensitivity in a colonization-independent manner. Meanwhile,
F. nucleatum
was found to induce an increase in specific secretory IgA through FomA.
PDF
