Does higher demand for medicinal plants lead to more harvest? Evidence from the dual trade of Nardostachy jatamansi and Fritillaria cirrhosa and Tibetan people’s harvesting behavior

IntroductionAs the demand for herbal medicines is surging worldwide, regions of medicinal plants are vulnerable to large-scale and unsustainable exploitation for commercial trade and use. Yet, we still lack the understanding about the relationship between indigenous people harvesting and trade practices of medicinal plants and their influencing factors for possible intervention measures.MethodsHere, we combined qualitative and quantitative methods to survey traders (N = 20) and local harvesters (N = 923) from nine Tibetan townships in Hongyuan county, Sichuan Province, on the eastern Qinghai-Tibetan plateau in China. Specifically, we elucidated the local value chain of medicinal plants trade and harvest of Nardostachy jatamansi and Fritillaria cirrhosa, and explored the factors influencing harvester’s willingness to harvest these plants. Furthermore, we empirically tested the constructs of the COM-B model (Capability, Opportunity, Motivation -Behavior) in predicting the sustainable harvesting behavior of medicinal plants.Results and DiscussionOur results revealed that the trade characteristics of N. jatamansi and F. cirrhosa were contrasting, and the sustainability of the former species was largely dependent on the latter one. Importantly, the traders’ practices were affected by the supply, while the harvesters’ willingness to harvest were mainly influenced by harvest incomes, past harvesting experience, and grassland tenure. Finally, though motivation was not directly affecting harvesting behavior, the harvesters’ ecological worldview indirectly affected their harvesting behavior, particularly through the mediation of the level of compliance of village rules and customs. Overall, our results provided crucial insights for the conservation and sustainable management of the valuable wild medicinal plants

MARVEL: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy: Study Rationale and Design

BACKGROUND Steroids have pleiotropic neuroprotective actions including the regulation of inflammation and apoptosis which may influence the effects of ischemia on neurons, glial cells, and blood vessels. The effect of low‐dose methylprednisolone in patients with acute ischemic stroke in the endovascular therapy era remains unknown. This trial investigates the efficacy and safety of low‐dose methylprednisolone (2 mg/kg IV for 3 days) as adjunctive therapy for patients with acute ischemic stroke undergoing endovascular therapy within 24 hours from symptom onset. METHODS The MARVEL(Methylprednisolone as Adjunctive Therapy for Acute Large Vessel Occlusion: A Randomized Double‐Blind, Placebo‐Controlled Trial in Patients Undergoing Endovascular Therapy) trial is an investigator‐initiated, prospective, randomized, double‐blind, placebo‐controlled multicenter clinical trial. Up to 1672 eligible patients with anterior circulation large‐vessel occlusion stroke presenting within 24 hours from symptom onset are planned to be consecutively randomized to receive methylprednisolone or placebo in a 1:1 ratio across 82 stroke centers in China. RESULTS The primary outcome is the ordinal shift in the modified Rankin scale score at 90 days. Secondary outcomes include 90‐day functional independence (modified Rankin scale score, 0–2). The primary safety end points include mortality rate at 90 days and symptomatic intracerebral hemorrhage within 48 hours of endovascular therapy. CONCLUSION The MARVEL trial will provide evidence of the efficacy and safety of low‐dose methylprednisolone as adjunctive therapy for patients with anterior circulation large‐vessel occlusion stroke undergoing endovascular therapy

Honokiol Crosses BBB and BCSFB, and Inhibits Brain Tumor Growth in Rat 9L Intracerebral Gliosarcoma Model and Human U251 Xenograft Glioma Model

BACKGROUND: Gliosarcoma is one of the most common malignant brain tumors, and anti-angiogenesis is a promising approach for the treatment of gliosarcoma. However, chemotherapy is obstructed by the physical obstacle formed by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Honokiol has been known to possess potent activities in the central nervous system diseases, and anti-angiogenic and anti-tumor properties. Here, we hypothesized that honokiol could cross the BBB and BCSFB for the treatment of gliosarcoma. METHODOLOGIES: We first evaluated the abilities of honokiol to cross the BBB and BCSFB by measuring the penetration of honokiol into brain and blood-cerebrospinal fluid, and compared the honokiol amount taken up by brain with that by other tissues. Then we investigated the effect of honokiol on the growth inhibition of rat 9L gliosarcoma cells and human U251 glioma cells in vitro. Finally we established rat 9L intracerebral gliosarcoma model in Fisher 344 rats and human U251 xenograft glioma model in nude mice to investigate the anti-tumor activity. PRINCIPAL FINDINGS: We showed for the first time that honokiol could effectively cross BBB and BCSFB. The ratios of brain/plasma concentration were respectively 1.29, 2.54, 2.56 and 2.72 at 5, 30, 60 and 120 min. And about 10% of honokiol in plasma crossed BCSFB into cerebrospinal fluid (CSF). In vitro, honokiol produced dose-dependent inhibition of the growth of rat 9L gliosarcoma cells and human U251 glioma cells with IC(50) of 15.61 µg/mL and 16.38 µg/mL, respectively. In vivo, treatment with 20 mg/kg body weight of honokiol (honokiol was given twice per week for 3 weeks by intravenous injection) resulted in significant reduction of tumor volume (112.70±10.16 mm(3)) compared with vehicle group (238.63±19.69 mm(3), P = 0.000), with 52.77% inhibiting rate in rat 9L intracerebral gliosarcoma model, and (1450.83±348.36 mm(3)) compared with vehicle group (2914.17±780.52 mm(3), P = 0.002), with 50.21% inhibiting rate in human U251 xenograft glioma model. Honokiol also significantly improved the survival over vehicle group in the two models (P<0.05). CONCLUSIONS/SIGNIFICANCE: This study provided the first evidence that honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. It suggested a significant strategy for offering a potential new therapy for the treatment of gliosarcoma

Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice

We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our strategy employed Cas9 and guide-sgRNA for the targeted disruption of intronic splicing-regulatory elements. We disrupted intronic splicing silencers (ISSs, including ISS-N1 and ISS + 100) of survival motor neuron (SMN) 2, a key modifier gene of SMA, to enhance exon 7 inclusion and full-length SMN expression in SMA iPSCs. Survival of splicing-corrected iPSC-derived motor neurons was rescued with SMN restoration. Furthermore, co-injection of Cas9 mRNA from Streptococcus pyogenes (SpCas9) or Cas9 from Staphylococcus aureus (SaCas9) alongside their corresponding sgRNAs targeting ISS-N1 into zygotes rescued 56% and 100% of severe SMA transgenic mice (Smn , SMN2 ). The median survival of the resulting mice was extended to >400 days. Collectively, our study provides proof-of-principle for a new strategy to therapeutically intervene in SMA and other RNA-splicing-related diseases. -/- tg/

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

Research on the integration level measurement and optimization path of industrial chain, innovation chain and service chain

The contemporary scientific and technological revolution and industrial transformation are accelerating an overall industrial evolution. The integration of industrial, innovation, and service chains (three-chain) has become an important measure for countries around the world for assessing and enhancing international competitiveness. Based on regional economic theory, industrial policy theory, and synergy theory, this study constructs an evaluation index to measure three-chain integration. A model to measure the degree of synergy among the three chains of the composite system is applied using sample data from Zhenjiang, China from 2012 to 2020. The relevant results are threefold. (1) The three chains of Zhenjiang are at a low level of synergy, which exhibits a downward trend. (2) The industrial chain's degree of synergy is the lowest, and must assume more responsibility for addressing the low three-chain integration level. (3) When examining the integration of any two chains, the integration level of the industrial and innovation chains is the highest. Finally, combined with the research results, optimization paths are proposed to promote three-chain integration. This research contributes to the field by integrating industrial, innovation, and service chains into a comprehensive research framework, constructing a universally applicable evaluation index system to empirically test the level of three-chain integration, and proposing optimal paths to provide scientific methods and decision-making reference to advance three-chain research

Hazard and Management of Emerging Environmental Pollutants in Food of China

The occurrence of emerging environmental pollutants brings new challenges to food safety in China, which needs to be systematically researched. This study focused on the distribution, hazard characteristics, and sources of antibiotics, endocrine disrupting chemicals (EDCs), perfluorinated compounds (PFCs), and microplastics (MPs) in major foods such as vegetables, fruits, grains, meat, aquatic products, eggs, and milk. It was found that fluoroquinolones showed a high detection rate in aquatic products, vegetables, and milk. Fluoroquinolones were mainly derived from the use of agricultural and veterinary drugs. Bisphenol A (one of phenolic EDCs) was frequently detected in canned food and aquatic products, and nonylphenol was mostly detected in aquatic products. Both EDCs were mainly from food packages. PFCs possessed a high detection rate in aquatic products, livestock meat, poultry meat, and eggs. PFCs were mainly from wastewater treatment plants and food packages. MPs showed a very high detection rate in aquatic products, which were mainly imported by contaminated environmental media. Ingestion of environmental emerging pollutants through food may lead to disease risk of human. Thus, it is recommended to monitor more types of emerging environmental pollutants in the scope of food safety, systematically plan the scientific rules of usage of the chemicals, and formulate a multi-departmental joint management and control mechanism to better cope with the issue of food safety caused by emerging environmental pollutants and effectively ensure food safety

A Reliable Method for Identification of Antibiotics by Terahertz Spectroscopy and SVM

Given the extensive use of antibiotics at present, the identification of antibiotics and production quality monitoring are of high importance. However, conventional antibiotic identification methods have a low sensitivity and a long detection time. Here, we propose an identification method that combines terahertz (THz) spectroscopy and chemometric technology. THz time-domain spectroscopy (THz-TDS) was performed for sixteen types of antibiotics, including β-lactam, cephalosporins, macrolides, and tetracyclines. The absorption spectra within the frequency range of 0.2–1.5 THz were calculated. For dimensionality reduction, principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) were implemented, respectively. The data after dimensionality reduction were input into a support vector machine (SVM). The model parameters were optimized through grid search (GS), genetic algorithm (GA), and particle swarm optimization (PSO) methods, and the optimal identification results were obtained after comparison across these methods. Experiments indicate a differentiation of the THz absorption spectra among the sixteen types of antibiotics. After dimensionality reduction, the training time of the model significantly decreased. The use of the t-SNE-PSO-SVM model achieved the highest average accuracy on the prediction set, which was 99.91%. Thus, our study does not only confirm that the t-SNE-PSO-SVM model proves to be a reliable method for antibiotics identification, but also confirms that the combination of THz-TDS and chemometric pattern recognition has great potential for drug detection

Potassium superoxide oxygen generation rate and carbon dioxide absorption rate in coal mine refuge chambers

The effects of the molding pressure of a KO2 oxygen plate and the initial concentration of CO2 on the oxygen generation rate, the oxygen generation efficiency, and the carbon dioxide absorption rate were studied using a YES-300 hydraulic press to alter the pressure when forming the oxygen plate used in a coal mine refuge chamber. In addition, changes in the initial concentration of CO2 used in the closed-box model were made by adjusting the CO2 supply system, and a CD-7 multi-function parameter instrument was employed to monitor and record the changes of O2 and CO2 concentration in the closed-box model. Results indicate that the oxygen generation rate of KO2 oxygen plates, the oxygen generation efficiency, and the carbon dioxide absorption rate decrease when there is an increase in the pressure used to mold the oxygen plates, but those values increase when the initial CO2 concentration increases. When the initial concentration of CO2 in the closed-box model is 3.5% and the forming pressure is 10 kN, the average oxygen generation rate of 15 g KO2 oxygen plate is 11.88 × 10−3 L/min, the oxygen generation efficiency is 80.3%, and the average CO2 absorption rate is 11.0 × 10−3 L/min. Compared with the condition where the initial CO2 concentration is 1.5%, the results show that average oxygen generation rate of oxygen plates increases by 88.9%, the oxygen generation efficiency increases by 88.9%, and the CO2 absorption rate increases by 100%. Keywords: Potassium superoxide, Oxygen generation rate, Oxygen generation efficiency, Carbon dioxide absorption rate, Concentratio