Dissecting pleiotropic functions of the wheat Green Revolution gene Rht-B1b in plant morphogenesis and yield formation.

The utilization of reduced plant height genes Rht-B1b and Rht-D1b, encoding homeologous DELLA proteins, led to the wheat Green Revolution (GR). However, the specific functions of GR genes in yield determination and the underlying regulatory mechanisms remained unknown. Here, we validated that Rht-B1b, as a representative of GR genes, affects plant architecture and yield component traits. Upregulation of Rht-B1b reduced plant height, leaf size and grain weight, but increased tiller number, tiller angle, spike number per unit area, and grain number per spike. Dynamic investigations showed that Rht-B1b increased spike number by improving tillering initiation rather than outgrowth, and enhanced grain number by promoting floret fertility. Rht-B1b reduced plant height by reducing cell size in the internodes, and reduced grain size or weight by decreasing cell number in the pericarp. Transcriptome analyses uncovered that Rht-B1b regulates many homologs of previously reported key genes for given traits and several putative integrators for different traits. These findings specify the pleiotropic functions of Rht-B1b in improving yield and provide new insights into the regulatory mechanisms underlying plant morphogenesis and yield formation.

Impact of "Green Revolution" gene Rht-B1b on coleoptile length of wheat.

Wheat coleoptile is a sheath-like structure that helps to deliver the first leaf from embryo to the soil surface. Here, a RIL population consisting of 245 lines derived from Zhou 8425B × Chinese Spring cross was genotyped by the high-density Illumina iSelect 90K assay for coleoptile length (CL) QTL mapping. Three QTL for CL were mapped on chromosomes 2BL, 4BS and 4DS. Of them, two major QTL QCL.qau-4BS and QCL.qau-4DS were detected, which could explain 9.1%-22.2% of the phenotypic variances across environments on Rht-B1 and Rht-D1 loci, respectively. Several studies have reported that Rht-B1b may reduce the length of wheat CL but no study has been carried out at molecular level. In order to verify that the Rht-B1 gene is the functional gene for the 4B QTL, an overexpression line Rht-B1b-OE and a CRISPR/SpCas9 line Rht-B1b-KO were studied. The results showed that Rht-B1b overexpression could reduce the CL, while loss-of-function of Rht-B1b would increase the CL relative to that of the null transgenic plants (TNL). To dissect the underlying regulatory mechanism of Rht-B1b on CL, comparative RNA-Seq was conducted between Rht-B1b-OE and TNL. Transcriptome profiles revealed a few key pathways involving the function of Rht-B1b in coleoptile development, including phytohormones, circadian rhythm and starch and sucrose metabolism. Our findings may facilitate wheat breeding for longer coleoptiles to improve seedling early vigor for better penetration through the soil crust in arid regions.

Analysis of the efficacy and safety of iodine-125 seeds implantation in the treatment of patients with inoperable early-stage non-small cell lung cancer.

PURPOSE: To evaluate the efficacy and safety of iodine-125 (125I) seeds implantation for inoperable early-stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: PubMed, Cochrane Library, Embase, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched from inception until April 2020. Data were collected concerning overall survival, short-term efficacy, and complications. Meta-analysis was performed using R software (version 3.6.3). RESULTS: Nine studies involving 308 patients were included. Meta-analysis showed that the 1-, 2-, and 3-year survival rates were 0.98% (95% CI: 0.95-0.99%), 0.83% (95% CI: 0.77-0.89%), and 0.65% (95% CI: 0.55-0.75%), respectively; short-term local control rate (LCR) and effective rates were 0.99% (95% CI: 0.98-1.00%) and 0.92% (95% CI: 0.83-0.98%), respectively; 1-, 2-, and 3-year LCRs were 0.96% (95% CI: 0.83-1.00%), 0.94% (95% CI: 0.85-0.99%), and 0.95% (95% CI: 0.76-1.00%), respectively. Sub-group analysis of the prescribed dose found that when the prescribed dose was > 120 Gy, short-term efficacy and 1-year LCR were increased significantly (p < 0.01). The incidence of bleeding, pneumothorax, and radiation lung injury was 0.14% (95% CI: 0.07-0.21%), 0.19% (95% CI: 0.11-0.28%), and 0.00% (95% CI: 0.00-0.03%), respectively. Two studies involving 106 patients compared 125I seeds combined with chemotherapy versus chemotherapy alone for NSCLC. Results showed that compared with chemotherapy alone, 125I seeds combined with chemotherapy could improve short-term LCR (RR = 1.34, 95% CI: 1.09-1.65%, p = 0.005) and short-term effective rate (RR = 1.49, 95% CI: 1.14-1.96%, p = 0.004). CONCLUSIONS: 125I seeds implantation is safe and effective approach for the treatment of inoperable early-stage NSCLC, but high-quality clinical research is still needed to further confirm the findings.

Dosimetry study of three-dimensional print template for 125I implantation therapy.

BACKGROUND: 125I seed implantation has been found to show good therapeutic effects on tumors. Recent studies showed that three-dimensional (3D) print template-assisted 125I seed implantation can optimize radiation dose distribution. This study aimed to compare the dose distribution differences in 125I seed implantation among 3D print noncoplanar template- (3DPNCT), 3D print coplanar template- (3DPCT) assisted implantation and traditional free-hand implantation. METHODS: We systematically searched the PubMed, EMbase, Cochrane Library, Wan Fang Med Online, China National Knowledge Infrastructure (CNKI) from the earliest to November 2020 without time or language restrictions. And the references of primary literature were also searched. The outcome measures were dosimetry and operation time. This meta-analysis was carried out using Stata 12.0. RESULTS: A total of 16 original articles were selected for inclusion. The differences of D90, D100, V90, and V100 values pre- and post-implantation with traditional free-hand implantation showed statistically significant (p < 0.05). The differences of D90, D100, V100, V150, V200, and D2cc of organs at risk (OAR) values pre- and post-implantation with 3D print template showed no statistically significant (p > 0.05). Compared with traditional free-hand implantation without any templates, 3D print template could improve postoperative D90 (Standard mean difference, SMD = 0.67, 95% confidence interval (CI) = 0.35 to 0.98, p < 0.001), D100 (SMD = 0.82, 95%CI = 0.40 to 1.23, p < 0.001), V90 (SMD = 1.48, 95%CI = 0.95 to 2.00, p < 0.001), V100 (SMD = 1.41, 95%CI = 0.96 to 1.86, p < 0.001), and reduce operation time (SMD = - 0.93, 95%CI = - 1.34 to - 0.51, p < 0.001). In three studies, both 3DPNCT and 3DPCT plans were designed for all patients. The prescribed dose and seed activity were same. Pooled analysis of D90, D100, V100, D2cc of OAR, number of seeds and number of needles showed no significant differences between 3DPNCT and 3DPCT groups (p > 0.05). However, in 3DPNCT group, V150 and V200 were increased (SMD = 0.35, 0.49; 95%CI = 0.04 to 0.67, 0.02 to 0.96; p = 0.028, 0.043); the number of through bone needles was reduced (SMD = - 1.03, 95%CI = - 1.43 to - 0.64, p < 0.001). CONCLUSIONS: Compared with traditional free-hand implantation, 3D print template-assisted 125I seeds implantation can optimize dose distribution and reduce the implantation time at the same time. Compared with 3D print coplanar template, 3D print noncoplanar template can increase the volume of high dose within tumor target and is more safer in the respect of puncture route.

Sublobar resection with intraoperative brachytherapy versus sublobar resection alone for early-stage non-small-cell lung cancer: a meta-analysis.

OBJECTIVES: The purpose of this study was to compare the clinical outcomes for sublobar resection (SR) or SR plus intraoperative brachytherapy (SRB) for clinical stage I non-small-cell lung cancer. METHODS: A systematic search was performed in the EMBASE, PubMed and Cochrane Library databases to identify related studies comparing SR to SRB. Data were collected on local recurrence (LR) as a primary outcome and regional or distant recurrence, overall survival and disease-free survival (DFS) as secondary outcomes. Meta-analysis was carried out using Stata 12.0. RESULTS: A total of 476 patients received SRB, and 617 received SR across 5 studies. Meta-analysis of LR, regional or distant recurrence, overall survival and disease-free survival rates showed no significant difference between SRB and SR groups. However, when biologically effective dose (BED) was >100 Gy, LR rate was lower in the SRB group than in the SR group (Relative risk [RR] = 0.143, 95% confidence interval [CI]: 0.051-0.397) (p < 0.001). When BED was <100 Gy, no significant difference was found in LR rate between SRB and SR groups (SRB versus SR: RR = 1.132, 95%CI: 0.704-1.821) (p = 0.608). CONCLUSIONS: Intraoperative brachytherapy was not associated with reduced risk of regional or distant metastasis or improved outcomes for patients with clinical stage I non-small-cell lung cancer; however, it might reduce the LR rate when BED was >100 Gy.

Clinical efficacy of xenon versus propofol: A systematic review and meta-analysis.

BACKGROUND: Interest in the anesthetic use of xenon, a noble gas, has waxed and waned for decades, and the clinical effects of xenon are still debated. We performed a meta-analysis to compare the clinical efficacy of xenon with that of propofol. METHODS: Electronic searches were performed through December 2017 using various databases, including PubMed, Embase, and the Cochrane Library. We identified thirteen trials that included a total of 817 patients. RESULTS: Patients treated with xenon had a lower bispectral index (BIS) (weighted mean difference (WMD): -6.26, 95% confidence interval (CI): -11.33 to -1.18, P = .02), a higher mean arterial blood pressure (MAP) (WMD: 7.00, 95% CI: 2.32-11.68, P = .003) and a lower heart rate (HR) (WMD: -9.45, 95% CI: -12.28 to -6.63, P < 0.00001) than propofol-treated patients. However, there were no significant differences between the 2 treatment groups in the effects of nondepolarizing muscular relaxants, the duration spent in the postanesthesia care unit (PACU) (WMD: -0.94, 95% CI: -8.79-6.91, P = .81), or the incidence of perioperative complications [assessed using the outcomes of postoperative nausea and vomiting (PONV) (relative risk (RR): 2.01, 95% CI: 0.79-5.11, P = .14), hypotension (RR: 0.62, 95% CI: 0.27 to 1.40, P = .25), hypertension (RR: 1.27, 95% CI: 0.73-2.21, P = .39) and bradycardia (RR: 1.00, 95% CI: 0.36-2.74, P = 1.00)]. CONCLUSION: In this meta-analysis of randomized controlled trials, we found that xenon treatment resulted in a higher MAP, a lower HR, and a smaller BIS index than treatment with propofol.

Tanshinone IIA Attenuates Sevoflurane Neurotoxicity in Neonatal Mice.

BACKGROUND: Sevoflurane is the most widely used inhalational anesthetic in pediatric medicine. Despite this, sevoflurane has been reported to exert potentially neurotoxic effects on the developing brain. Clinical interventions and treatments for these effects are limited. Tanshinone IIA (Tan IIA), extracted from Salvia miltiorrhiza (Danshen), has been documented to alleviate cognitive decline in traditional applications. Therefore, we hypothesized that preadministration of Tan IIA may attenuate sevoflurane-induced neurotoxicity, suggesting that Tan IIA is a new and promising drug capable of counteracting the effects of cognitive dysfunction produced by general anesthetics. METHODS: To test this hypothesis, neonatal C57 mice (P6) were exposed to 3% sevoflurane for 2 hours with or without Tan IIA pretreatment at a dose of 10 mg/kg or 20 mg/kg for 3 consecutive days. Cognitive behavior tests such as open field tests and fear conditioning were performed to evaluate locomotor and cognitive function at P31 and P32. At P8, other separate tests, including TdT mediated dUTP Nick End Labeling (TUNEL) assay, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, and electron microscopy, were performed. The mean differences among groups were compared using 1-way analysis of variance followed by Bonferroni post hoc multiple comparison tests. RESULTS: Repeated exposure to sevoflurane leads to significant cognitive impairment in mice, which may be explained by increased apoptosis, overexpression of neuroinflammatory markers, and changes in synaptic ultrastructure. Interestingly, preadministration of Tan IIA ameliorated these neurocognitive deficits, as shown by increased freezing percentages on the fear conditioning test (sevoflurane+Tan IIA [20 mg/kg] versus sevoflurane, mean difference, 19, 99% confidence interval for difference, 6.4-31, P < .0001, n = 6). The treatment also reduced the percentage of TUNEL-positive nuclei (sevoflurane versus sevoflurane+Tan IIA [20 mg/kg], 2.6, 0.73-4.5, P = .0004, n = 6) and the normalized expression of cleaved caspase-3 (sevoflurane versus sevoflurane+Tan IIA [20 mg/kg], 0.27, 0.02-0.51, P = .0046, n = 5). Moreover, it attenuated the production of the neuroinflammatory mediators interleukin (IL)-1ß and IL-6 (normalized sevoflurane versus sevoflurane+Tan IIA [20 mg/kg]: IL-1ß: 0.75, 0.47-1.0; P < .0001; IL-6: 0.66, 0.35-0.97; P < .0001; n = 10 per group). Finally, based on measurements of postsynaptic density, the treatment preserved synaptic ultrastructure (sevoflurane+Tan IIA [20 mg/kg] versus sevoflurane, 42, 20-66; P < .0001; n = 12 per group). CONCLUSIONS: These results indicate that Tan IIA can alleviate sevoflurane-induced neurobehavioral abnormalities and may decrease neuroapoptosis and neuroinflammation.

Effects of ghrelin on pulmonary NOD2 mRNA expression and NF-κB activation when protects against acute lung injury in rats challenged with cecal ligation and puncture.

BACKGROUND: Many studies have shown that ghrelin can down-regulate inflammatory cytokine expression via the inhibition of NF-κB activity and therefore, its administration to septic patients is considered beneficial. However, our knowledge of ghrelin's effects on the upstream activators of the NF-κB pathway, such as NOD2, is still limited. This study aimed to investigate the possible involvement of the NOD2 signaling pathway in the anti-inflammatory effects of ghrelin. METHODS: Twenty-four male SD rats received cecal ligation and puncture (CLP) or sham operation, followed by infusion of saline or ghrelin. The lungs were harvested 6h after CLP or sham operation and analyzed for lung histopathology, neutrophil infiltration, inflammatory cytokines (TNF-α, and IL-6), NOD2 mRNA expression, and activation of NF-κB. Furthermore, survival was recorded for ten days in additional groups of rats. RESULTS: Compared with sham group, neutrophil infiltration, TNF-α and IL-6 levels, NOD2 mRNA expression, as well as NF-κB activation in lungs from rats undergoing CLP were significantly increased. After the administration of ghrelin, all inflammatory parameters analyzed were lower than those without ghrelin following CLP. In addition, ghrelin improved survival after CLP. CONCLUSION: Our results indicate that in a CLP model of sepsis, the beneficial effects that ghrelin has on inflammatory outcomes are mediated at least in part through inhibition of NOD2 expression upstream of NF-κB.