Blended controlled-release nitrogen fertilizer increases rice post-anthesis nitrogen accumulation, translocation and nitrogen-use efficiency.

One-time application of blended controlled-release nitrogen fertilizer (CRN) has the potential to solve the difficulty of top-dressing fertilizer in the cultivation of rice and reduce the cost of CRN fertilizer application. However, its effects on rice dry matter and nitrogen (N) accumulation and translocation, yield and N-use efficiency (NUE) remain uncertain. Field experiments were carried out at three sites (Mingguang, Chaohu, and Guichi) in the Yangtze River Delta in China to compare the effects of the conventional split applications of urea and the blended CRN and on post-anthesis dry matter and N accumulation and translocation, yield, and NUE in rice at 0, 60, 120, 180, and 240 kg N ha-1. The results showed that at the equal N application rates, compared under the conventional N fertilizer treatment, the blended CRN application significantly increased the rice yield by an average of 0.9-6.9%, mainly due to increase the number of spikelets per panicle. The highest yield achieved with blended CRN treatment occurred at 200 kg N ha-1, with an NUE of 45.9%. Moreover, in comparison to the conventional N fertilizer, the blended CRN treatment increased pre-anthesis N translocation (Pre-NT) by 1.0-19.8%, and the contribution of pre-NT to grain N by 0.2-8.7%, and NUE by 3.2-28.4%. Meanwhile, the blended CRN treatment reduced labor costs by 1800 Yuan ha-1 and enhanced the economic gains by 21.5-68.8%. Therefore, one-time application of blended CRN ≤ 200 kg N ha-1 application rate improved rice yield, NUE, and economic profit compared to equivalent rates of split applied conventional N fertilizers.

Black Phosphorus Nanosheets Protect Neurons by Degrading Aggregative α-syn and Clearing ROS in Parkinson's Disease.

Although evidence indicates that the abnormal accumulation of α-synuclein (α-syn) in dopamine neurons of the substantia nigra is the main pathological feature of Parkinson's disease (PD), no compounds that have both α-syn antiaggregation and α-syn degradation functions have been successful in treating the disease in the clinic. Here, it is shown that black phosphorus nanosheets (BPNSs) interact directly with α-syn fibrils to trigger their disaggregation for PD treatment. Moreover, BPNSs have a specific affinity for α-syn through van der Waals forces. And BPNSs are found to activate autophagy to maintain α-syn homeostasis, improve mitochondrial dysfunction, reduce reactive oxygen species levels, and rescue neuronal death and synaptic loss in PC12 cells. It is also observed that BPNSs penetrate the blood-brain barrier and protect against dopamine neuron loss, alleviating behavioral disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model and hA53T α-syn transgenic mice. Together, the study reveals that BPNSs have the potential as a novel integrated nanomedicine for clinical diagnosis and treatment of neurological diseases.

Effect of homemade peanut oil consumption during pregnancy on low birth weight and preterm birth outcomes: a cohort study in Southwestern China.

BACKGROUND: Homemade peanut oil is widely consumed in rural areas of Southwestern China, which is easily contaminated by aflatoxins (AFs) and associated with adverse birth outcomes. OBJECTIVE: To identify the effect of exposure to homemade peanut oil consumption on low birth weight (LBW), preterm birth (PB) and other associated factors. METHODS: A prospective cohort study was conducted among pregnant women in Guangxi province, Southwestern China. Information of all eligible women on homemade peanut oil consumption and potential factors associated with LBW and PB was collected, and all were followed up until delivery. The effect of homemade peanut oil exposure was analyzed using multiple logistic regression models using the directed acyclic graph (DAG) approach. RESULTS: Of 1611 pregnant women, 1316 (81.7%) had consumed homemade peanut oil, and the rates of LBW and PB were 9.7% and 10.0%, respectively. Increased risks of LBW and PB in women with homemade peanut oil consumption were found with aORs of 1.9 (95% CI 1.1-3.2) and 1.8 (95% CI 1.1-3.0), respectively. Women with a history of PB or LBW were 3-5 times more likely to have higher rates of LBW or PB compared with those without this type of history. The odds of PB were approximately double in those taking medicine during pregnancy. Advanced maternal age, lack of physical exercise during pregnancy, passive smoking, or pregnancy complications were also more likely to have a higher risk of LBW. CONCLUSIONS: Homemade peanut oil consumption was a potential risk factor for both LBW and PB, of which health authorities who are responsible for food safety of the country should pay more attention to providing recommendation for oil consumption during pregnancy.

Main findings: Homemade peanut oil consumption was associated with increased risk of low birth weight and preterm birth, in addition to advanced age, adverse obstetric histories, and health risk behaviors during pregnancy in a county in Southwestern China.Added knowledge: This study identifies the direct and total effects of homemade peanut oil consumption on low birth weight and preterm birth and explains the factors associated with low birth weight and preterm birth in a county in Southwestern China.Global health impact for policy and action: Evidence of associated risk factors for low birth weight and preterm birth should be informed to the community, and precautionary policies for the protection of aflatoxin exposure during pregnancy are needed.

Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear. This study aimed to determine the mechanism of ALA in regulating ferroptosis in PD models. Results showed that ALA could ameliorate motor deficits in PD models and regulate iron metabolism by upregulating ferroportin (FPN) and ferritin heavy chain 1 (FTH1) and downregulating iron importer divalent metal transporter 1 (DMT1). Moreover, ALA decreased the accumulation of reactive oxygen species (ROS) and lipid peroxidation, rescued mitochondrial damage, and prevented ferroptosis effectively by inhibiting the downregulation of glutathione peroxidase 4 (GPX4) and cysteine/glutamate transporter (xCT) in PD. Mechanistic study indicated that the activation of SIRT1/NRF2 pathway was involved in the upregulation effect of GPX4 and FTH1. Thus, ALA ameliorates motor deficits in PD models by regulating iron metabolism and mitigating ferroptosis through the SIRT1/NRF2 signaling pathway.

The optimum economic nitrogen rate of blended controlled-release nitrogen fertilizer for rice in the Chanoyu watershed in the Yangtze River Delta, China.

Introduction: The application of controlled-release nitrogen fertilizer (CRN) has become an important production method to achieve high crop yield and ecological safety. However, the rate of urea-blended CRN for rice is usually determined by conventional urea, and the actual rate is still unclear. Methods: A five-year field experiment was carried out in the Chaohu watershed in the Yangtze River Delta to study rice yield, N fertilizer utilization efficiency (NUE), ammonia (NH3) volatilization and economic benefit under the four urea-blended CRN treatments with a 4:3:3 ratio applied at one time (60, 120, 180, 240 kg/hm2, CRN60, CRN120, CRN180, CRN240), four conventional N fertilizer treatments (N60, N120, N180, N240) and a control without N fertilizer (N0). Results and Discussion: The results showed that the N released from the blended CRNs could well satisfy the N demand of rice growth. Similar to the conventional N fertilizer treatments, a quadratic equation was used to model the relationship between rice yield and N rate under the blended CRN treatments. The blended CRN treatments increased rice yield by 0.9-8.2% and NUE by 6.9-14.8%, respectively, compared with the conventional N fertilizer treatments at the same N application rate. The increase in NUE in response to applied blended CRN was related to the reduction in NH3 volatilization. Based on the quadratic equation, the five-year average NUE under the blended CRN treatment was 42.0% when rice yield reached the maximum, which was 28.9% higher than that under the conventional N fertilizer treatment. Among all treatments, CRN180 had the highest yield and net benefit in 2019. Considering the yield output, environmental loss, labor and fertilizer costs, the optimum economic N rate under the blended CRN treatment in the Chaohu watershed was 180-214 kg/hm2, compared with 212-278 kg/hm2 under the conventional N fertilizer treatment. The findings suggest that blended CRN improved rice yield, NUE and economic income while decreasing NH3 volatilization and negative environmental outcomes.

Effects of Partial Replacement of Nitrogen Fertilizer with Organic Fertilizer on Rice Growth, Nitrogen Utilization Efficiency and Soil Properties in the Yangtze River Basin.

Cake fertilizer and dairy manure were used as experimental materials to carry out a 9-year (2012-2020) field experiment in the main rice production areas in the Yangtze River basin. Different fertilization modes were used (no fertilization, CK; chemical fertilizer application alone, HY; reduced fertilization with chemical fertilizer application, RF; cake fertilizer replacement of nitrogen fertilizer, CFR; and dairy manure replacement of nitrogen fertilizer, DMR). Changes in the total rice yield, yield components, absorption of nitrogen, soil pH, organic matter, total nitrogen, and soil bulk density under different fertilization treatments were analyzed. The results show that organic fertilizer replacement leads to a stable and high rice yield. The 9-year average rice yields of the CFR and DMR treatments were 60.0% and 61.5% higher than that of CK. The nitrogen uptake of the CFR and DMR treatments was also higher than that of the other treatments. The nitrogen recovery efficiency in the current season could be increased by 16.37-22.89%, and after 9 years of testing, the soil total nitrogen contents of CFR and DMR increased by 0.23-0.85 g·kg-1 compared to the other treatments. The available P and K contents of DMR increased by 30.17 mg·kg-1 and 22.02 mg·kg-1 compared with HY, respectively. The soil bulk density was reduced by 0.08 g·cm-3. Generally, the effects of dairy manure replacement were better than those of cake fertilizer. This is an important method that can be used to fertilize the soil and foster sustainable soil utilization in the rice-growing area of the Yangtze River Basin, as a long-term partial replacement for chemical nitrogen fertilizer.

Successful Retreatment with Crizotinib After Crizotinib-Induced Liver Failure in ALK-Positive Advanced Lung Adenocarcinoma: A Case Report.

Patients with non-small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements are treated with crizotinib. However, treatment with crizotinib is often discontinued owing to hepatotoxicity. Herein, we report a case of crizotinib-induced liver failure that was successfully treated. A 70-year-old woman complained of a cough with blood in her sputum and presented to our hospital in September 2020. Imaging examination revealed a mass in the middle and lower lobes of the right lung invading the right pulmonary artery and metastases to the right hilar lymph nodes and pleura. A stage IVa (cT4N1M1a) lung adenocarcinoma with ALK fusion was diagnosed. The patient received crizotinib, an ALK tyrosine kinase inhibitor and achieved partial remission. However, she suffered from acute liver failure, which led to the cessation of treatment. The patient was started on a liver protection treatment, and the liver function subsequently recovered. One year later, crizotinib was readministered at a half-dose because of disease progression, and the patient achieved stable disease without hepatotoxicity for 9 months. Therefore, the patient benefited from crizotinib without hepatotoxicity one year after acute liver failure caused by crizotinib.

Circular RNA hsa_circ_0057452 facilitates keloid progression by targeting the microRNA-1225-3p/AF4/FMR2 family member 4 axis.

The circular RNA, hsa_circ_0057452, is highly expressed in keloids, but its specific mechanism of action remains unknown. The levels of hsa_circ_0057452, microRNA (miR)-1225-3p, and AF4/FMR2 family member 4 (AFF4) in keloid tissues and keloid fibroblasts (KFs) were determined using quantitative reverse transcription-polymerase chain reaction. Changes in KFs viability, proliferation, apoptosis, and migration were investigated using the cell counting kit-8, bromodeoxyuridine, flow cytometry, and Transwell assays. Luciferase, RNA immunoprecipitation, and RNA pull-down assays were performed to identify the binding relationship among hsa_circ_0057452, miR-1225-3p, and AFF4. We found that hsa_circ_0057452 and AFF4 expression levels were upregulated, whereas miR-1225-3p expression levels were downregulated in keloids. Knockdown of hsa_circ_0057452 or AFF4 suppressed the viability, proliferation, and migration of KFs and induced apoptosis, whereas hsa_circ_0057452 overexpression and miR-1225-3p knockdown showed the opposite trend. Furthermore, hsa_circ_0057452 affected the biological behavior of KFs by releasing AFF4 via sponging of miR-1225-3p. Therefore, our results show that hsa_circ_0057452 promotes keloid progression by targeting miR-1225-3p and regulating AFF4 levels.

Atrial fibrillation driver identification through regional mutual information networks: a modeling perspective.

PURPOSE: Effective identification of electrical drivers within remodeled tissue is a key for improving ablation treatment for atrial fibrillation. We have developed a mutual information, graph-based approach to identify and propose fault tolerance metric of local efficiency as a distinguishing feature of rotational activation and remodeled atrial tissue. METHODS: Voltage data were extracted from atrial tissue simulations (2D Karma, 3D physiological, and the Multiscale Cardiac Simulation Framework (MSCSF)) using multi-spline open and parallel regional mapping catheter geometries. Graphs were generated based on varied mutual information thresholds between electrode pairs and the local efficiency for each graph was calculated. RESULTS: High-resolution mapping catheter geometries can distinguish between rotational and irregular activation patterns using the derivative of local efficiency as a function of increasing mutual information threshold. The derivative is decreased for rotational activation patterns comparing to irregular activations in both a simplified 2D model (0.0017 ± 1 × 10-4 vs. 0.0032 ± 1 × 10-4, p < 0.01) and a more realistic 3D model (0.00092 ± 5 × 10-5 vs. 0.0014 ± 4 × 10-5, p < 0.01). Average local efficiency derivative can also distinguish between degrees of remodeling. Simulations using the MSCSF model, with 10 vs. 90% remodeling, display distinct derivatives in the grid design parallel spline catheter configuration (0.0015 ± 5 × 10-5 vs. 0.0019 ± 6 × 10-5, p < 0.01) and the flower shaped open spline configuration (0.0011 ± 5 × 10-5 vs. 0.0016 ± 4 × 10-5, p < 0.01). CONCLUSION: A decreased derivative of local efficiency characterizes rotational activation and varies with atrial remodeling. This suggests a distinct communication pattern in cardiac rotational activation detectable via high-resolution regional mapping and could enable identification of electrical drivers for targeted ablation.

A Survey of Chinese Pig Farms and Human Healthcare Isolates Reveals Separate Human and Animal Methicillin-Resistant Staphylococcus aureus Populations.

There has been increasing concern that the overuse of antibiotics in livestock farming is contributing to the burden of antimicrobial resistance in people. Farmed animals in Europe and North America, particularly pigs, provide a reservoir for livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA ST398 lineage) found in people. This study is designed to investigate the contribution of MRSA from Chinese pig farms to human infection. A collection of 483 MRSA are isolated from 55 farms and 4 hospitals in central China, a high pig farming density area. CC9 MRSA accounts for 97.2% of all farm isolates, but is not present in hospital isolates. ST398 isolates are found on farms and hospitals, but none of them formed part of the "LA-MRSA ST398 lineage" present in Europe and North America. The hospital ST398 MRSA isolate form a clade that is clearly separate from the farm ST398 isolates. Despite the presence of high levels of MRSA found on Chinese pig farms, the authors find no evidence of them spilling over to the human population. Nevertheless, the ST398 MRSA obtained from hospitals appear to be part of a widely distributed lineage in China. The new animal-adapted ST398 lineage that has emerged in China is of concern.

Internet behaviors and associated factor among Chinese primary school students / 中国学校卫生

Objective@#To analyze Internet behaviors of children and adolescents and their influencing factors, and to provide scientific basis for health education guidance and prevention measures.@*Methods@#A stratified cluster sampling method was used. From January to June 2019, 30 955 primary school students in 16 provinces (municipalities), from eastern, central, and western economic zones of China were selected to conduct a questionnaire survey, regarding general demographics, diet and exercise, tobacco, alcohol and sleep, Internet and electronics usage, etc.@*Results@#Among them, 43.1% of students had never been online with girls (44.7%) higher than boys (41.8%)(χ2=21.04, P<0.01); 1.3% of students reported online time for more than 4 hours a day, boys were significantly higher than girls(χ2=15.87, P<0.01); Internet addiction was detected in 2.4% of elementary school students, with boys (3.0%) higher than girls(1.7%)(χ2=331.77, P<0.01), and the trend increases with grade. With sixth grade (3.3%) were significantly higher than children from the first grade (0.8%) and other grades(χ2=163.96, P<0.01). Children’s tendency to Internet addiction was 11.9%, of which boys were 13.0% and girls were 10.6%, boys were significantly higher than girls(χ2=117.66, P<0.01). Pearson correlation analysis revealed that, after controlling gender age, boarding school, family relationship, single parents and regrouped families, smoking, drinking sugary drinks, eating fried foods, and left-behind were positively related to Intenet addiction(r=0.06, 0.07, 0.27, 0.44, 0.07, 0.11, 0.09, P<0.01), while medium and high intensity sports, effective physical education, health education in school, AIDS education and parental restrictions on TV and computer games, were negatively associated with internet addiction(r=-0.74, -0.65, -0.04, -0.05, -0.63, P<0.01).@*Conclusion@#The internet addiction of Chinese primary school students is common and increases by year. High-intensity, high-density sports, effective physical education, and health education could help prevent Internet addiction among children.

[Alpha-lipoic acid inhibits the expression of α-synuclein in PC12 cells induced by 6-hydroxydopamine and its mechanism].

Objective To investigate the effects of α-lipoic acid (α-LA) on the expression of α-synuclein(α-syn)in cellular models of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) and its mechanism. Methods PC12 cells were induced by 6-OHDA to establish the cellular models of PD, which was treated with α-LA. Cell viability was detected using MTT assay. The contents of intracellular iron and malondialdehyde (MDA) were detected by colorimetry.The level of intracellular reactive oxygen species (ROS) was detected by 2, 7-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Western blot analysis was performed to detect the level of α-syn protein. Results Compared with the normal control group, the cell viability of the model group was significantly decreased, the contents of intracellular iron and MDA and the level of ROS were significantly increased, and the expression level of α-syn was significantly increased; compared with the model group, the cell viability of the α-LA treat group was significantly increased, the contents of intracellular iron and MDA and the level of ROS were significantly decreased, and the expression level of α-syn was significantly decreased. Conclusion α-LA can inhibit the overexpression of α-syn and attenuate the damage of PC12 cells induced by 6-OHDA, which may be related to the decrease of contents of intracellular iron and oxidative stress level by α-LA.

miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks.

miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR occurs through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase because GSK3B promotes degradation of both CDC25A and cyclin D1, but CDC25A and cyclin D1 have an opposite effect on HRR. A negative correlation of expression levels between miR-21 and GSK3ß exists in a subset of human tumors. Our results not only elucidate miR-21-mediated radioresistance, but also provide potential new targets for improving radiotherapy.

Novel Podophyllotoxin Derivatives as Partial PPARγ Agonists and their Effects on Insulin Resistance and Type 2 Diabetes.

Peroxisome proliferator-activated receptor γ (PPARγ) is recognized as a key regulator of insulin resistance. In this study, we searched for novel PPARγ agonists in a library of structurally diverse organic compounds and determined that podophyllotoxin exhibits partial agonist activity toward PPARγ. Eight novel podophyllotoxin-like derivatives were synthesized and assayed for toxicity and functional activity toward PPARγ to reduce the possible systemic toxic effects of podophyllotoxin and to maintain partial agonist activity toward PPARγ. Cell-based transactivation assays showed that compounds (E)-3-(hydroxy(3,4,5-trimethoxyphenyl)methyl)-4-(4(trifluoromethyl)styryl)dihydrofuran-2(3H)-one (3a) and (E)-4-(3-acetylstyryl)-3-(hydroxyl (3,4,5-trimethoxyphenyl)methyl)dihydrofuran-2(3H)-one (3f) exhibited partial agonist activity. An experiment using human hepatocarcinoma cells (HepG2) that were induced to become an insulin-resistant model showed that compounds 3a and 3f improved insulin sensitivity and glucose consumption. In addition, compounds 3a and 3f significantly improved hyperglycemia and insulin resistance in high-fat diet-fed streptozotocin (HFD-STZ)-induced type 2 diabetic rats at a dose of 15 mg/kg/day administered orally for 45 days, without significant weight gain. Cell toxicity testing also showed that compounds 3a and 3f exhibited weaker toxicity than pioglitazone. These findings suggested that compounds 3a and 3f improved insulin resistance in vivo and in vitro and that the compounds exhibited potential for the treatment of type 2 diabetes mellitus.

Complex dynamics in an alcoholism model with the impact of Twitter.

A novel alcoholism model which involves impact of Twitter is formulated. It is shown that the model has multiple equilibria. Stability of all the equilibria are obtained in terms of the basic reproductive number R0. Using the center manifold theory, the occurrence of backward and forward bifurcation for a certain defined range of R0 are established. Furthermore, the existence of Hopf bifurcation is also established by regarding the transmission coefficient ß as the bifurcation parameter. Numerical simulations and sensitivity analysis on a few parameters are also carried out. Our results show that Twitter can serve as a good indicator of alcoholism model and affect the spread of the drinking.

Lessons learned using different mouse models during space radiation-induced lung tumorigenesis experiments.

Unlike terrestrial ionizing radiation, space radiation, especially galactic cosmic rays (GCR), contains high energy charged (HZE) particles with high linear energy transfer (LET). Due to a lack of epidemiologic data for high-LET radiation exposure, it is highly uncertain how high the carcinogenesis risk is for astronauts following exposure to space radiation during space missions. Therefore, using mouse models is necessary to evaluate the risk of space radiation-induced tumorigenesis; however, which mouse model is better for these studies remains uncertain. Since lung tumorigenesis is the leading cause of cancer death among both men and women, and low-LET radiation exposure increases human lung carcinogenesis, evaluating space radiation-induced lung tumorigenesis is critical to enable safe Mars missions. Here, by comparing lung tumorigenesis obtained from different mouse strains, as well as miR-21 in lung tissue/tumors and serum, we believe that wild type mice with a low spontaneous tumorigenesis background are ideal for evaluating the risk of space radiation-induced lung tumorigenesis, and circulating miR-21 from such mice model might be used as a biomarker for predicting the risk.

GPRC5A suppresses protein synthesis at the endoplasmic reticulum to prevent radiation-induced lung tumorigenesis.

GPRC5A functions as a lung tumour suppressor to prevent spontaneous and environmentally induced lung carcinogenesis; however, the underlying mechanism remains unclear. Here we reveal that GPRC5A at the endoplasmic reticulum (ER) membrane suppresses synthesis of the secreted or membrane-bound proteins including a number of oncogenes, the most important one being Egfr. The ER-located GPRC5A disturbs the assembly of the eIF4F-mediated translation initiation complex on the mRNA cap through directly binding to the eIF4F complex with its two middle extracellular loops. Particularly, suppression of EGFR by GPRC5A contributes significantly to preventing ionizing radiation (IR)-induced lung tumorigenesis. Thus, GPRC5A deletion enhances IR-promoted EGFR expression through an increased translation rate, thereby significantly increasing lung tumour incidence in Gprc5a(-/-) mice. Our findings indicate that under-expressed GPRC5A during lung tumorigenesis enhances any transcriptional stimulation through an active translational status, which can be used to control oncogene expression and potentially the resulting related disease.