Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion

The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Linkage mechanism of public transport subsidy: considering passenger ridership, cost, fare and service quality

Under the long-term implementation of the low fare policy for public transport in China, the phenomenon of unsustainable subsidies is increasingly obvious. We take into account three related stakeholders including the public, operators and government, and comprehensively consider various factors affecting public transport subsidies, and establish a linkage mechanism of the subsidy based on passenger ridership, cost, fare and service quality. We propose a combination forecasting model (CFM) composed of quadratic exponential smoothing model (QESM) and Grey theory model (GM) to forecast passenger ridership. The results show that the CFM improves the forecast accuracy of passenger ridership, the factors considered in the linkage mechanism are more comprehensive, and the results are reasonable. By using this linkage mechanism, the government or operators can establish long-term or mid-term development plans to provide a systematic and theoretical reference, which is conducive to the healthy and stable development of public transport

Improving liming mode for remediation of Cd-contaminated acidic paddy soils: Identifying the optimal soil pH, model and efficacies

Liming has been widely taken to remediate Cd-contaminated acidic paddy soils, whereas liming mode involving in the relevant optimal soil pH, model and efficacies remain unclear. Both soil and field liming experiments were conducted to improve liming mode for precise remediation of Cd-contaminated acidic paddy soils. Soil batch liming experiments indicated soil DTPA-Cd and CaCl2-Cd were piecewise linearly correlated to soil pH with nodes of 6.8–8.0, and decreased respectively by 15.3%37.7% and 80.7%93.8% (P < 0.05) when soil pH raised over the nodes, indicating an appropriate target soil pH 7.0 for liming. Stepwise linear regression revealed that liming ratio (LR, kg ha−1) could be estimated from soil basal pH (pH0) and the interval to the target soil pH (ΔpH), as [LR=exp(1.10 ×ΔpH+0.61 ×pH0-4.98), R2 = 0.97, n = 42, P < 0.01]. The model exhibited high prediction accuracy (95.2%), low mean estimation error (−0.02) and root mean square error (0.20). Field liming experiment indicated liming to target pH decreased respectively soil CaCl2-Cd by 95.2–98.0% and rice grain Cd by 59.8–80.6% (P < 0.01), whereas uninfluenced rice grain yield. Correlation analysis and structural equation models (SEM) demonstrated that great reduction in Cd phytoavailability was mainly attributed to the transformation of soil water-soluble and exchangeable Cd to carbonate-bound Cd and Fe/Mn oxides-bound Cd and reduced Cd in iron plaque as increasing soil pH. However, rice grain Cd of 50% samples met national food safety standards limit of China (0.2 mg kg−1) due to the high soil Cd level (0.8 mg kg−1). In conclusion, liming to target soil pH 7.0 could be considered as a precise and effective remediation mode for Cd-contaminated acidic paddy soils and complementary practices should be implemented for severe pollution. Our results could provide novel insights on precise liming remediation of Cd-contaminated acidic paddy soils

Novel Insights into the circRNA-Modulated Developmental Mechanism of Western Honey Bee Larval Guts

Circular RNAs (circRNAs) are a class of novel non-coding RNAs (ncRNAs) that play essential roles in the development and growth of vertebrates through multiple manners. However, the mechanism by which circRNAs modulate the honey bee gut development is currently poorly understood. Utilizing the transcriptome data we obtained earlier, the highly expressed circRNAs in the Apis mellifera worker 4-, 5-, and 6-day-old larval guts were analyzed, which was followed by an in-depth investigation of the expression pattern of circRNAs during the process of larval guts development and the potential regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 1728 expressed circRNAs were detected in the A. mellifera larval guts. Among the most highly expressed 10 circRNAs, seven (novel_circ_000069, novel_circ_000027, novel_circ_000438, etc.) were shared by the 4-, 5-, and 6-day-old larval guts. In addition, 21 (46) up-regulated and 22 (27) down-regulated circRNAs were, respectively, screened in the Am4 vs. Am5 (Am5 vs. Am6) comparison groups. Additionally, nine DEcircRNAs, such as novel_circ_000340, novel_circ_000758 and novel_circ_001116, were shared by these two comparison groups. These DEcircRNAs were predicted to be transcribed from 14 and 29 parental genes; these were respectively annotated to 15 and 22 GO terms such as biological regulation and catalytic activity as well as 16 and 21 KEGG pathways such as dorsoventral axis formation and apoptosis. Moreover, a complicated competing endogenous RNA (ceRNA) network was observed; novel_circ_000838 in the Am4 vs. Am5 comparison group potentially targeted ame-miR-6000a-3p, further targeting 518 mRNAs engaged in several developmental signaling pathways (e.g., TGF-beta, hedgehog, and wnt signaling pathway) and immune pathways (e.g., phagosome, lysosome, and MAPK signaling pathway). The results demonstrated that the novel_circ_000838-ame-miR-6000a-3p axis may plays a critical regulatory part in the larval gut development and immunity. Furthermore, back-splicing sites of six randomly selected DEcircRNAs were amplified and verified by PCR; an RT-qPCR assay of these six DEcircRNAs confirmed the reliability of the used high-throughput sequencing data. Our findings provide a novel insight into the honey bee gut development and pave a way for illustration of the circRNA-modulated developmental mechanisms underlying the A. mellifera worker larval guts

Contrasting pathways of carbon sequestration in paddy and upland soils

Paddy soils make up the largest anthropogenic wetlands on earth, and are characterized by a prominent potential for organic carbon (C) sequestration. By quantifying the plant- and microbial-derived C in soils across four climate zones, we identified that organic C accrual is achieved via contrasting pathways in paddy and upland soils. Paddies are 39%–127% more efficient in soil organic C (SOC) sequestration than their adjacent upland counterparts, with greater differences in warmer than cooler climates. Upland soils are more replenished by microbial-derived C, whereas paddy soils are enriched with a greater proportion of plant-derived C, because of the retarded microbial decomposition under anaerobic conditions induced by the flooding of paddies. Under both land-use types, the maximal contribution of plant residues to SOC is at intermediate mean annual temperature (15–20°C), neutral soil (pH~7.3), and low clay/sand ratio. By contrast, high temperature (~24°C), low soil pH (~5), and large clay/sand ratio are favorable for strengthening the contribution of microbial necromass. The greater contribution of microbial necromass to SOC in waterlogged paddies in warmer climates is likely due to the fast anabolism from bacteria, whereas fungi are unlikely to be involved as they are aerobic. In the scenario of land-use conversion from paddy to upland, a total of 504 Tg C may be lost as CO2 from paddy soils (0–15 cm) solely in eastern China, with 90% released from the less protected plant-derived C. Hence, preserving paddy systems and other anthropogenic wetlands and increasing their C storage through sustainable management are critical for maintaining global soil C stock and mitigating climate change

Genetic Diversity, Rather than Cultivar Type, Determines Relative Grain Cd Accumulation in Hybrid Rice

Cadmium (Cd) is a toxic element, and rice is known to be a leading source of dietary Cd for people who consume rice as their main caloric resource. Hybrid rice has dominated rice production in southern China and has been adopted worldwide. The characteristics of high yield heterosis of rice hybrids makes the public think intuitively that the hybrid rice accumulates more Cd in grain than do inbred cultivar. A detailed understanding of the genetic basis of grain Cd accumulation in hybrids and developing Cd-safe rice are of the top priorities for hybrid rice breeders at present. In this study, we investigated genetic diversity and grain Cd levels in 617 elite rice hybrids collected from the middle and lower Yangtze River Valley in China and 68 inbred cultivars from around the world. We found that there are large variations in grain Cd accumulation in both the hybrids and their inbred counterparts. However, we found similar grain Cd levels in the rice hybrids to the levels in indica rice inbreds, suggesting that the hybrids do not accumulate more Cd than do the inbred rice cultivars. Further analysis revealed that the high heritability of Cd accumulation in the grain and the single indica population structure increases the risk of Cd over-accumulation in hybrid rice. The genetic effects of Cd-related QTLs, which have been identified in related Cd-QTL mapping studies, were also determined in the hybrid rice population. Four QTLs were identified as being associated with the variation in grain Cd levels; three of these loci exhibited obvious indica-japonica differentiations. Our study will provide a better understanding of grain Cd accumulations in hybrid rice, and pave the way towards effective breeding for high-yielding, low grain-Cd hybrids in the future