Search

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest. Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained. Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered.

Space nuclear reactors are becoming popular in deep space exploration owing to their advantages of high-power density and stability. Following the fourth-generation nuclear reactor technology, a conceptual design of the dual drum-controlled space molten salt reactor (D2-SMSR) is proposed. The reactor concept uses molten salt as fuel and heat pipes for cooling. A new reactivity control strategy that combines control drums and safety drums was adopted. Critical physical characteristics such as neutron energy spectrum, neutron flux distribution, power distribution and burnup depth were calculated. Flow and heat transfer characteristics such as natural convection, velocity and temperature distribution of the D2-SMSR under low gravity conditions were analyzed. The reactivity control effect of the dual-drums strategy was evaluated. Results showed that the D2-SMSR with a fast spectrum could operate for 10 years at the full power of 40 kWth. The D2-SMSR has a high heat transfer coefficient between molten salt and heat pipe, which means that the core has a good heat-exchange performance. The new reactivity control strategy can achieve shutdown with one safety drum or three control drums, ensuring high-security standards. The present study can provide a theoretical reference for the design of space nuclear reactors.

ABSTRACT: Inosine monophosphate (IMP) plays a significant role in meat taste, yet the molecular mechanisms controlling IMP deposition in muscle tissues still require elucidation. The present study systematically and comprehensively explores the molecular network governing IMP deposition in different regions of Jingyuan chicken muscle. Two muscle groups, the breast and leg, were examined as test materials. Using nontargeted metabolomic sequencing, we screened and identified 20 metabolites that regulate IMP-specific deposition. We maintained regular author and institution formatting, used clear, objective, and value-neutral language, and avoided biased or emotional language. We followed a consistent footnote style and formatting features and used precise word choice with technical terms where appropriate. Out of these, 5 were identified as significant contributors to the regulation of IMP deposition. We explained technical term abbreviations when first used and ensured a logical flow of information with causal connections between statements. The results indicate that PGM1, a key enzyme involved in synthesis, is higher in the breast muscle compared to the leg muscle, which may provide an explanation for the increased deposition of IMP in the breast muscle. We aimed for a clear structure with logical progression, avoided filler words, and ensured grammatical correctness. The activity of key enzymes (PKM2, AK1, AMPD1) involved in this process was higher in the breast muscle than in the leg muscle. In the case of IMP degradation metabolism, the activity of its participating enzyme (PurH) was lower in the breast muscle than in the leg muscle. These findings suggest that the increased deposition of IMP in Jingyuan chickens' breast muscle may result from elevated metabolism and reduced catabolism of key metabolites. In summary, a metaomic strategy was utilized to assess the molecular network regulation mechanism of IMP-specific deposition in various segments of Jingyuan chicken. These findings provide insight into genetic improvement and molecular breeding of meat quality traits for top-notch broilers.

Obstructive sleep apnea (OSA), a frequently under-diagnosed sleep disorder, may lead to future poor health, performance, and wellbeing. Increased OSA prevalence has been reported in individuals who have had a head injury.We systematically searched EMBASE, PSYCINFO, WEB OF SCIENCE, COCHRANE and PUBMED to 18th June 2022. OSA prevalence and demographic data was extracted according to PRISMA guidelines from 14 eligible studies with 6,116 participants, with study quality assessed using the modified Downs and Black Score.Meta-analysis of proportions yielded a pooled OSA prevalence of 30.0% (95% confidence interval (CI), 24.0–36.0%) with significant heterogeneity between studies (I2 = 94.4%, p

Summary: Background: Exercise is advised for young adults with elevated blood pressure, but no trials have investigated efficacy at this age. We aimed to determine whether aerobic exercise, self-monitoring and motivational coaching lowers blood pressure in this group. Methods: The study was a single-centre, open, two-arm, parallel superiority randomized clinical trial with open community-based recruitment of physically-inactive 18–35 year old adults with awake 24 h blood pressure 115/75mmHg-159/99 mmHg and BMI37 weeks) to the intervention group, who received 16-weeks aerobic exercise training (three aerobic training sessions per week of 60 min per session at 60–80% peak heart rate, physical activity self-monitoring with encouragement to do 10,000 steps per day and motivational coaching to maintain physical activity upon completion of the intervention. The control group were sign-posted to educational materials on hypertension and recommended lifestyle behaviours. Investigators performing statistical analyses were blinded to group allocation. The primary outcome was 24 h awake ambulatory blood pressure (systolic and diastolic) change from baseline to 16-weeks on an intention-to-treat basis. Clinicaltrials.gov registered on March 30, 2016 (NCT02723552). Findings: Enrolment occurred between 30/06/2016-26/10/2018. Amongst the 203 randomized young adults (n = 102 in the intervention group; n = 101 in the control group), 178 (88%; n = 76 intervention group, n = 84 control group) completed 16-week follow-up and 160 (79%; n = 68 intervention group, n = 69 control group) completed 52-weeks follow-up. There were no group differences in awake systolic (0·0 mmHg [95%CI, -2·9 to 2·8]; P = 0·98) or awake diastolic ambulatory blood pressure (0·6 mmHg [95%CI, -1·4. to 2·6]; P = 0·58). Aerobic training increased peak oxygen uptake (2·8 ml/kg/min [95%CI, 1·6 to 4·0]) and peak wattage (14·2watts [95%CI, 7·6 to 20·9]) at 16-weeks. There were no intervention effects at 52-weeks follow-up. Intepretation: These results do not support the exclusive use of moderate to high intensity aerobic exercise training for blood pressure control in young adults. Funding: Wellcome Trust, British Heart Foundation, National Institute for Health Research, Oxford Biomedical Research Centre.

Pig farmers' willingness to recover production under the COVID-19 pandemic shock is significant to recover live pigs' supply in China in 2020. Increasing farmers' willingness to recover pig production contributes to enhance pig supply, stabilize the pig and pork market, and to improve pig farmers' income. This research studies the determinants of pig farmers' willingness to recover production under COVID-19 pandemic shock by applying survey data of 201 farmers in Huai'an City and Lin'an City and a logit regression model. The estimation results show that a farmer's risk perception, the duration time of a farmer's feed supply under COVID-19 pandemic shock, whether or not being a cooperative member, and a farmer's knowledge on government's policy designed to encourage pig production, a farmer's education level and production experience are the key determinants to a farmer's willingness to recover pig production. Thus, it's important for policymakers to solve the problems for farmers to get access to feed during the pandemic, to encourage the development of cooperatives, as well as to issue and advocate policies to encourage pig production. The study contributes to the scant literature by providing fresh empirical evidences on determinants of farmers' willingness to recover pig production. It has significance to farmers and governments to enhance farmers' willingness to recover production, which contributes to secure pig supply in China after the COVID-19 pandemic.

The quality and integrity of available dam data are critical for broad efforts to produce fine-scale assessments of their basin cycle, water quality, and other environmental and ecological effects. This study proposes a dam identification method in broad areas, object identification based on remote sensing images, and geographical analysis. First, we extracted dam candidate regions from broad surface water raster data at a spatial resolution of 30 m. Second, we trained and adjusted the multi-target recognition models using the dam sample from Google images, scanning dam candidate regions and extracting highly confidential dam positions. Moreover, we analyzed the location characteristics of the dams and used three geographical constraints to reduce background region overestimation further. The proposed framework was tested across an area of 13 265 km2 (Aomori, Kanagawa, and Okinawa) and yielded promising results, which reduced the candidate areas to 13.43% of the total water area. We validate the framework results using the available high-resolution historical image series available on Google Earth. The framework recalled 112 dams at a rate of 91.06%, with a precision rate of 80%. We simultaneously identified 39 dams that were not recorded in the known datasets. Our results reveal that the overall framework is reliable for automatic and rapid dam detection with a foundation of open geographic products. The framework proposed in this paper is the new attempt to combine deep learning target detection technology and spatial analysis with dam identification in broad areas.

Background: Newly-developed suction-based airway clearance devices potentially provide a novel way to improve outcome in patients with foreign body airway obstruction. We conducted a randomised controlled crossover manikin trial to compare the efficacy and usability of two of these devices with abdominal thrusts. Methods: We randomised participants from a UK medical school to one of six groups which determined the order in which participants attempted the three techniques (abdominal thrusts; LifeVac, Nesconset, New York, USA; Dechoker, Concord North Carolina, USA). Randomisation was performed using an online randomisation system. Following brief training, participants sought to remove a foreign body airway obstruction from a manikin using the allocated technique. The primary outcome was successful removal of the foreign body. Usability was assessed in a questionnaire following the three simulations. Results: We randomised and analysed data from 90 participants (58% male; 86% aged 18−29 years). Compared with abdominal thrusts, successful foreign body airway obstruction removal was achieved more frequently in manikins in the LifeVac group (odds ratio 47.32, 95% CI 5.75–389.40) but not in the Dechoker group (odds ratio 1.22, 95% CI 0.60–2.47). The usability of LifeVac and abdominal thrusts were generally evaluated more positively than the Dechoker. Conclusion: In this manikin study, we found that, compared with abdominal thrusts, the success rate for foreign body airway obstruction removal was higher in the LifeVac group but not in the Dechoker group.

Farmers' production behaviour is a key to ensuring the safety and quality of their final products, and cooperatives play an important role in shaping that behaviour. This paper aims to explore the determinants of pig farmers' safe production behaviour, giving special focus from the perspective of cooperatives' services. This study adopted cross sectional survey data from 27 pig cooperatives and their 540 farmers in China to test the influence of cooperatives' services on farmers' safe production behaviour. The hypotheses were tested using a logit regression model. The findings indicated that although the number of services is not a key determinant of farmers' safe production behaviour, service quality matters. When a cooperative is strongly capable of involving more farmers in certain services, and provides certain services in more frequency, member farmers behave more safely. The results also show that veterinarian and pig-selling services play an important role in ensuring farmers' safe production behaviour. For this study, the quality of cooperatives' services is implied to have a positive impact on farmers' safe production behaviour. Leaders/managers of cooperatives must try to improve the quality of their services instead of merely attempting to provide a large number of services. For government officials and policy makers, designing policies that encourage cooperatives to improve their service quality is important. This research contributes to the scant literature on how cooperative services could help farmers engage in safer production behaviour, which would improve the safety of pork products in the future.

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) signaling is transient and spatially confined in live cells. How this pattern of signaling regulates transmitter release and hormone secretion has not been addressed. We devised an optogenetic approach to control PI(4,5)P2 levels in time and space in insulin-secreting cells. Combining this approach with total internal reflection fluorescence microscopy, we examined individual vesicle-trafficking steps. Unlike long-term PI(4,5)P2 perturbations, rapid and cell-wide PI(4,5)P2 reduction in the plasma membrane (PM) strongly inhibits secretion and intracellular Ca2+ concentration ([Ca2+]i) responses, but not sytaxin1a clustering. Interestingly, local PI(4,5)P2 reduction selectively at vesicle docking sites causes remarkable vesicle undocking from the PM without affecting [Ca2+]i. These results highlight a key role of local PI(4,5)P2 in vesicle tethering and docking, coordinated with its role in priming and fusion. Thus, different spatiotemporal PI(4,5)P2 signaling regulates distinct steps of vesicle trafficking, and vesicle docking may be a key target of local PI(4,5)P2 signaling in vivo.

The dorsomedial prefrontal cortex (dmPFC) plays a crucial role in social cognitive functions, including perspective-taking. Although perspective-taking has been linked to self-control, the mechanism by which the dmPFC might facilitate self-control remains unclear. Using the multimodal neuroimaging dataset from the Human Connectome Project (Study 1, N =978 adults), we established a reliable association between the dmPFC and self-control, as measured by discounting rate—the tendency to prefer smaller, immediate rewards over larger, delayed ones. Experiments (Study 2, N = 36 adults) involving high-definition transcranial direct current stimulation showed that anodal stimulation of the dmPFC reduces the discounting of delayed rewards and decreases the congruency effect in egocentric but not allocentric perspective in the visual perspective-taking tasks. These findings suggest that the dmPFC promotes self-control by inhibiting the egocentric perspective, offering new insights into the neural underpinnings of self-control and perspective-taking, and opening new avenues for interventions targeting disorders characterized by impaired self-regulation.

Introduction: Breast cancer is the most common cancer among women. The surgical treatment of breast cancer has transitioned progressively from radical mastectomy to breast-conserving surgery. In this meta-analysis, we are aiming to compare oncoplastic breast-conserving surgery (OS) with conventional breast-conserving surgery (BCS) in terms of efficacy and safety. Methods: We searched Medline, Web of Science, Embase, Cochrane databases, Clinicaltrial.gov, and CNKI until April 30, 2024. Data from cohort studies and randomized controlled trials (RCTs) were included. Outcomes included primary outcomes (re-excision, local recurrence, positive surgical margin, mastectomy), secondary outcomes and safety outcomes. The Cochrane Risk of Bias Assessment Tool and Newcastle-Ottawa Scale were used to evaluate the quality of outcomes. Results: Our study included 52 studies containing 46,835 patients. Primary outcomes comprise re-excision, local recurrence, positive surgical margin, and mastectomy, there were significant differences favoring OS over BCS (RR 0.68 [0.56, 0.82], RR 0.62 [0.47, 0.82], RR 0.76 [0.59, 0.98], RR 0.66 [0.44, 0.98] respectively), indicating superior efficacy of OS. Additionally, OS demonstrated significant aesthetic benefits (RR 1.17 [1.03, 1.33] and RR 1.34 [1.18, 1.52]). While total complications were significantly fewer in the OS group (RR 0.70 [0.53, 0.94]), the differences in specific complications were not significant. Furthermore, subgroup analyses were conducted based on nationality, sample size, quality, and type. Conclusion: OS demonstrates either superior or at least comparable outcomes across various aspects when compared to BCS.

Background: In the realm of Chinese medicine, quality control and pharmacodynamics are crucial to ensure the consistency in scaled-up process from the laboratory to commercial operations. This study aims to analyse bioactivity consistency between laboratory observations and commercial processes. Method: The preparation of BPAid (5: 2: 9: 1 for Uncaria rhynchophylla (UR): Pueraria thomsonii (PT): Panax notoginseng (PN): Alisma orientale (AO) was divided into three methods: laboratory-scale maceration (BPAidM), industrial-scale flash extract method (BPAidFE), decoction method (BPAidD). The vasodilatory and antihypertensive effects of the extracts were examined through ex vivo and in vivo studies. The chemical fingerprint of each extract was analysed using tri-step FTIR spectroscopy, and UPLC-MS/MS was used for standard marker quantification. Results: BPAidM exhibited the highest vasodilatory effect, followed by BPAidFE, and BPAidD with EC50 values of 11.25 ± 2.30 mg/mL, 39.23 ± 12.55 mg/mL, 24.33 ± 6.26 mg/mL, and 198.71 ± 127.21 mg/mL: RMAX values of 106.53 ± 7.95%, 82.92 ± 5.22%, 76.35 ± 4.51%, and 60.62 ± 5.7%, respectively. In in vivo antihypertensive studies, all extracts significantly reduced the blood pressure of Spontaneously Hypertensive rats (SHRs). The tri-step FTIR revealed the presence of phenolic compounds, esters, and saccharides in BPAid extracts. BPAidM contained the highest total standard marker in the UPLC-MS/MS quantification, followed by BPAidFE, and BPAidD. Conclusion: Ultimately, the flash extract technique is recommended to produce BPAid to meet the global demand.

Given the scarcity of water resources and the ever-growing demand, effective water flow management becomes crucial. The Lake Urmia Basin, a critical region in Iran, faces severe water scarcity exacerbated by climatic changes, land use alterations, over-extraction of groundwater, and mismanagement. This study evaluates the water resource balance by integrating carrying capacity and water footprint models to assess sustainable water management practices. Utilizing the InVEST model, water provisioning ecosystem services have been estimated as the supply, while the ecological footprint method quantifies water demand across various sectors. Three scenarios are evaluated: continuation of the current situation, an ideal scenario with substantial reductions in water consumption and pollution, and implementation of operational programs. The findings reveal significant water deficits in certain sub-basins, highlighting the need for a fundamental revision of resource allocation based on each region’s ecological capacity. Lake Urmia, the central nucleus of the basin, has experienced a significant size reduction, approximately 10 % of its original size, from the early 1990s to 2018, due to climatic changes, land use alterations, over-extraction of groundwater, and mismanagement. The environmental deficit in some sub-basins raises serious concerns, even in the best scenario where ecological footprint reduction is considered. These results underscore the effectiveness of ecosystem-based comprehensive capacity analysis for sustainable watershed development. This research offers a unified spatial system for quantifying ecological footprints and land resilience, providing critical insights into addressing water scarcity and supporting holistic regional planning.

Avoiding the upward-bending hook is a highly pressing and challenging task in the field of similar aluminum alloys friction stir lap welding (FSLW). To enhance formation quality and then obtain the welded lap joint with high tensile shear load, a novel impacting flow FSLW (IF-FSLW) process based on the X-shape reverse-threaded pin was proposed in this study. Three welding tools with different tool geometry parameters were developed to analyze how the locations of the materials accumulated zone (MAZ) influenced the joint formation and the joint loading capacity, and 7B04 aluminum alloys were chosen as research subject. Results showed that the horizontally-impacting and vertically-impacting effects of MAZ on and above the original lap interface made the hook respectively present the forky structure at the end and the downward-bending morphology, and the horizontally-impacting effect of MAZ made the stir zone (SZ) have a protruding morphology near the MAZ. Under the tensile fracture mode, the IF-FSLW joint under configuration A had a greatly heightened tensile shear load under the combined actions of the downward-bending hook and the enlarged SZ. The tensile shear load of IF-FSLW joint reached 8.62 kN/mm under the reasonable combination of tool geometry parameters and welding process parameters. The IF-FSLW process by the X-shape reverse-threaded pin provides an effective way to obtain a superb-strength lap joint of aluminum alloys.

Based on engineered cell/exosome technology and various skin-related animal models, exosomal microRNA (miRNA)-based therapies derived from natural exosomes have shown good therapeutic effects on nine skin diseases, including full-thickness skin defects, diabetic ulcers, skin burns, hypertrophic scars, psoriasis, systemic sclerosis, atopic dermatitis, skin aging, and hair loss. Comparative experimental research showed that the therapeutic effect of miRNA-overexpressing exosomes was better than that of their natural exosomes. Using a dual-luciferase reporter assay, the targets of all therapeutic miRNAs in skin cells have been screened and confirmed. For these nine types of skin diseases, a total of 11 animal models and 21 exosomal miRNA-based therapies have been developed. This review provides a detailed description of the animal models, miRNA therapies, disease evaluation indicators, and treatment results of exosomal miRNA therapies, with the aim of providing a reference and guidance for future clinical trials. There is currently no literature on the merits or drawbacks of miRNA therapies compared with standard treatments.

Background/Purpose: Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies worldwide. While several environmental risk factors for cSCC are well established, there is conflicting evidence on cigarette smoking (and its potential causal effect) and cSCC risk. Furthermore, it is unclear if these potential associations represent causal, modifiable risk factors for cSCC development. This study aims to assess the nature of the associations between cigarette smoking traits (smoking initiation, amount smoked, and lifetime smoking exposure) and cSCC risk using two-sample Mendelian randomization analyses. Methods: Genetic instruments, based on common genetic variants associated with cigarette smoking traits (P

This study investigated the low-cycle fatigue (LCF) behavior of Twinning induced plasticity (TWIP) steel based on the twin bridge shear specimen and cyclic shear loading condition. The cyclic shear experiments were conducted with different strain amplitudes, and we compared their softening and hardening behaviors, cyclic stress-strain curves, and fatigue life. Through studying the crack morphology and the damage mechanism of shear specimens the role of cyclic shear stress on the damage evolution of TWIP under cyclic shear conditions was shown. The results indicate that the cyclic hardening and softening capacities of TWIP steel are highly affected by the strain amplitude. With increasing the load amplitude, the hardening rate increases, and its fatigue life is negatively correlated with the strain amplitude. Meanwhile, the hardening rate is positively correlated with the strain amplitude, and the softening rate is negatively correlated. The magnitude of strain amplitude affects the ratio of cyclic softening and cyclic hardening periods. Through analyzing the obtained microstructure characteristics, it is found that there is a high density of dislocations around the crack zone which causes the final failure of TWIP.

Background: The Chinese herbal compound Lian-Gui-Ning-Xin-Tang (LGNXT), composed of 9 herbs, has a significant antiarrhythmic effect. Previous studies have confirmed that preventing intracellular Ca2+ overload and maintaining intracellular Ca2+ homeostasis may be the important antiarrhythmic mechanisms of LGNXT. Recent studies are focused on elucidating the mechanisms and pharmacodynamic substances of LGNXT. Purpose: 1) To investigate the antiarrhythmic mechanisms of LGNXT; 2) to explore the association of pharmacodynamics (PD) and pharmacokinetics (PK) of the potential pharmacodynamic substances in LGNXT to further verify the mechanisms of action. Methods: First, pharmacodynamic studies were conducted to determine the effect of LGNXT in arrhythmia at the electrophysiological, molecular, and tissue levels, and the “effect–time” relationship of LGNXT was further proposed. Next, an HPLC-MS/MS method was established to identify the “dose–time” relationship of the 9 potential compounds. Combining the “effect–time” and “dose–time” curves, the active ingredients closely related to the inhibition of inflammation, oxidative stress, and energy metabolism were identified to further verify the mechanisms and pharmacodynamic substances of LGNXT. Results: Pretreatment with LGNXT could delay the occurrence of arrhythmias and reduce their duration and severity. LGNXT exerted antiarrhythmic effects by inhibiting MDA, LPO, IL-6, and cAMP; restoring Cx43 coupling function; and upregulating SOD, Ca2+-ATPase, and Na+-K+-ATPase levels. PK-PD association showed that nobiletin, methylophiopogonanone A, trigonelline, cinnamic acid, liquiritin, dehydropolisic acid, berberine, and puerarin were the main pharmacodynamic substances responsible for inhibiting the inflammatory response in arrhythmia. Methylophiopogonanone A, dehydropalingic acid, nobiletin, trigonelline, berberine, and puerarin in LGNXT exerted antiarrhythmic effects by inhibiting oxidative stress. Dehydropalingic acid, berberine, cinnamic acid, liquiritin, puerarin, trigonelline, methylophiopogonanone A, nobiletin, and tetrahydropalmatine exerted antiarrhythmic effects by inhibiting the energy-metabolism process. Conclusions: LGNXT had a positive intervention effect on arrhythmias, especially ventricular tachyarrhythmias, which could inhibit inflammation, oxidative stress, and energy metabolism; positively stabilize the structure, and remodify the function of myocardial cell membranes. Additionally, the PD–PK association study revealed that methylophiopogonanone A, berberine, trigonelline, liquiritin, puerarin, tetrahydropalmatine, nobiletin, dehydropachymic acid, and cinnamic acid directly targeted inflammation, oxidative stress, and energy metabolism, which could be considered the pharmacodynamic substances of LGNXT. Thus, the antiarrhythmic mechanisms of LGNXT were further elucidated.

This paper focuses on identifying voltage sag-sensitive loads within unknown load type or when the load is already in operation. To achieve this, a new method of sensitive load identification based on power quality monitoring data is proposed. Firstly, the active power RMS monitoring data is used as the base data. The Hodrick-Prescott filtering and sliding mean segmentation are used to divide the period of the voltage sag event. Next, based on the division result, the differences of steady-state power quality monitoring data before and after each event are calculated as the dataset. The dynamic K-means is used to divide various load action areas. Finally, the voltage tolerance curves of each action area are fitted and compared with the preset curves, then according to the constituted rules in this paper, the type of sensitive load contained by user is recognized. The feasibility and accuracy of the proposed method are verified by analyzing the simulation examples and actual power quality monitoring data.© 2017 Elsevier Inc. All rights reserved.

Chitosan is a biocompatible, non-toxic and renewable natural basic polysaccharide that can be cross-linked and reacted with Ce(IV) to form a physiologically active chitosan-Ce(IV) complex. To investigate this novel complex and its potential to hydrolyze phosphate ester bonds, chitosan-cerium complex microspheres resin (CS-CCMR) was prepared from chitosan and ceric ammonium nitrate by reversed-phase suspension cross-linking polymerization. CS-CCMR was characterized, its ability to hydrolyze disodium p-nitrobenzene phosphate (PNPP2Na) and organophosphorus pesticides was investigated, and the hydrolytic mechanism was explored. CS-CCMR was composed of dark yellow microspheres with smooth surfaces and dense pores. It was found that CS-CCMR contained 4.507 mg/g Ce(IV), indicating that coordination polymerization between Ce(IV) and chitosan was successful. The presence of Ce(IV) in CS-CCMR was confirmed by multiple analytical methods and it was found that coordination of Ce(IV) by chitosan was mediated by the nitrogen atom of the amino group and the oxygen atom of the hydroxyl group of chitosan. It was shown that CS-CCMR efficiently hydrolyzed the phosphate ester bonds of PNPP2Na and five organophosphorus pesticides. Hydrolysis of PNPP2Na is potentially accomplished by charge neutralization and nucleophilic substitution. The mechanism of parathion degradation by CS-CCMR involves modification of the nitro group to give aminoparathion, followed by cleavage of the P–O bond to generate diazinphos. Consequently, the novel chitosan-Ce(IV) complex exhibits great efficiency for hydrolysis of phosphate ester bonds and CS-CCMR is expected to be developed as an agent to reduce the possibility of contamination of fruit and vegetable drinks by organophosphorus pesticides.

The prevalence of calcific aortic valve disease (CAVD) remains substantial while there is currently no medical therapy available. Forkhead box O1 (FOXO1) is known to be involved in the pathogenesis of cardiovascular diseases, including vascular calcification and atherosclerosis; however, its specific role in calcific aortic valve disease remains to be elucidated. In this study, we identified FOXO1 significantly down-regulated in the aortic valve interstitial cells (VICs) of calcified aortic valves by investigating clinical specimens and GEO database analysis. FOXO1 silencing or inhibition promoted VICs osteogenic differentiation in vitro and aortic valve calcification in Apoe−/− mice, respectively. We identified that FOXO1 facilitated the ubiquitination and degradation of RUNX2, which process was mainly mediated by SMAD-specific E3 ubiquitin ligase 2 (SMURF2). Our discoveries unveil a heretofore unacknowledged mechanism involving the FOXO1/SMURF2/RUNX2 axis in CAVD, thereby proposing the potential therapeutic utility of FOXO1 or SMURF2 as viable strategies to impede the progression of CAVD.

Radiation therapy (RT) nowadays is a main treatment modality of cancer. To ensure the therapeutic efficacy of patients, accurate dose distribution is often required, which is a time-consuming and labor-intensive process. In addition, due to the differences in knowledge and experience among participants and diverse institutions, the predicted dose are often inconsistent. In last several decades, artificial intelligence (AI) has been applied in various aspects of RT, several products have been implemented in clinical practice and confirmed superiority. In this paper, we will review the research of AI in dose prediction, focusing on the progress in deep learning (DL).

Fugu (Takifugu rubripes) is a commercially important fish in aquaculture in China, Japan, and Korea. Male fugu are highly prized compared to females because the mature testes are regarded as a delicacy, thus all-male populations are preferred in aquaculture. However, the molecular mechanisms underlying sex differentiation in fugu remain largely unclear. Progestins, which are mediated by the progesterone receptor, can initiate spermatogenesis or ovarian differentiation in teleosts. To explore the effect of progestin blockage on fugu sex differentiation, the antiprogestin mifepristone (RU486) (500 μg/g of feed) was administrated to fugu larvae from 30 to 90 days after hatching (dah). Histological analysis revealed that RU486 treatment resulted in complete masculinization (100 %) of the XX fugu population at both 120 (RU486 withdrawal 30 days) and 150 (RU486 withdrawal 60 days) dah, and RU486-treated XX gonads developed testes-like structure. Gonadal transcriptomic analysis at 90 dah identified 3595 genes that were differentially expressed (DEGs) between the control and treated groups. Among them, the expression of steroid hormone biosynthesis-related genes (e.g., cyp11c1, cyp19a1a, and hsd17b1) and other key genes (e.g., gsdf, dmrt1, and foxl2) were altered in the gonads of RU486-treated groups. Most of the DEGs were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to sex differentiation, such as neuroactive ligand-receptor interaction, ovarian steroidogenesis, and steroid hormone biosynthesis pathways. The expression of cyp19a1a, foxl2, cyp11c1, gsdf, dmrt3, and dmrt1 at 50, 70, and 90 dah was further assessed. The expression levels of gsdf, dmrt1, and cyp11c1 were increased, and the expression levels of cyp19a1a and foxl2 were decreased in the gonads of XX larvae in RU486 treated groups. These results demonstrated for the first time that RU486 induced masculinization in XX fugu and provided a theoretical basis for further studies of the regulatory role of progestins in sex differentiation in teleosts.

Rapid and accurate determination of pigment content is important for quality inspection of spinach leaves during storage. This study aimed to use hyperspectral imaging at two spectral ranges (visible/near-infrared, VNIR: 400–1000 nm; NIR: 900–1700 nm) to simultaneously determine the pigment (chlorophyll a, chlorophyll b, total chlorophyll, and carotenoids) content in spinach stored at different durations and conditions (unpackaged and packaged). Partial least squares (PLS), back propagation neural network (BPNN) and convolutional neural network (CNN) were used to establish single-task and multi-task regression models. Single-task CNN (STCNN) models and multi-task CNN (MTCNN) models obtained better performances than the other models. The models using VNIR spectra were superior to those using NIR spectra. The overall results indicated that hyperspectral imaging with multi-task learning could predict the quality attributes of spinach simultaneously for spinach quality inspection under various storage conditions. This research will guide food quality inspection by simultaneously inspecting multiple quality attributes.

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.

Continuous application of fermented organic fertilizer can improve soil quality, while the performance of nitrogen (N) in the improved soils is rarely investigated. To investigate the fate of applied N in the soils with organic management history, the 15NH2CO15NH2 (15N abundance of 19.6 %) was employed as the exogenous N source to conduct an experiment in the Chinese cabbage and tomato rotation system under plastic shed condition. The cultivated soils have received 15-year of effective microorganism (EM) fermented organic fertilizer (EM-OF), N, P, K inorganic fertilizer (NPK-IF) and no fertilizer (NoF). The 15N use by cabbage and tomato, the soil 15N forms, as well as the 15N distribution were observed. Results showed that the 15N use efficiency of cabbage in the EM-OF, NPK-IF and NoF soils were 55.1 %, 37.3 % and 26.6 % respectively, showing significant (p ≤ 0.05) differences. The succeeding crop tomato could take up the soil residual 15N, and the highest 15N reuse efficiency was 7.1 % that detected in the NoF soil. The total 15N loss (6.0 %) from the rotation system was the lowest in the EM-OF soil, compared to that in the NPK-IF and NoF soils. It was concluded that the long-term fermented organic fertilizer applied soils can reduce urea 15N loss from plastic shed agriculture, mainly through improving the in-season crop 15N use efficiency.

Summary: Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.

Micro/nano topological modification is critical for improving the in vivo behaviors of bone implants, regulating multiple cellular functions. Titania (TiO2) nanotubes show the capacity of promoting osteoblast-related cell differentiation and induce effective osseointegration, serving as a model material for studying the effects of micro/nano-topological modifications on cells. However, the intracellular signaling pathways by which TiO2 nanotubes regulate the osteogenic differentiation of stem cells are not fully defined. Thy-1 (CD90), a cell surface glycoprotein anchored by glycosylphosphatidylinositol, has been considered a key molecule in osteoblast differentiation in recent years. Nevertheless, whether the micro/nano topology of the implant surface leads to changes in Thy-1 is unknown, as well as whether these changes promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, TiO2 nanotubes of various diameters were prepared by adjusting the anodizing voltage. qPCR and immunoblot were carried out to assess the mechanism by which TiO2 nanotubes regulate Thy-1. The results revealed Ti plates harboring TiO2 nanotubes ∼100-nm diameter (TNT-100) markedly upregulated Thy-1. Subsequently, upregulated Thy-1 promoted the activation of Fyn/RhoA/MLC Ⅱ/F-actin axis, which enhanced the nuclear translocation of YAP. After Thy-1 knockdown by siRNA, the Fyn/RhoA/MLC Ⅱ/F-actin axis was significantly inhibited and TiO2 nanotubes showed decreased effects on osteogenic differentiation. Therefore, Thy-1 upregulation might be a major mechanism by which micro/nano-topological modification of TiO2 nanotubes promotes osteogenic differentiation in BMSCs. This study provides novel insights into the molecular mechanism of TiO2 nanotubes, which may help design improved bone implants for clinical application.

Germplasm resource innovation is a crucial factor for cultivar development, particularly within the context of hybrid rice breeding based on the three-line system. Quan 9311A, a cytoplasmic male sterile (CMS) line, has been successfully cultivated using rice restoration materials and extensively employed as a female parent in hybrid breeding program in China. This line was developed by crossing the CMS line Zhong 9A with a two-line restorer line 93-11, with the intention of eliminating the restoring ability of 93-11 while retaining the sterility gene WA352c from Zhong 9A. Quan 9311A effectively amalgamates the most favorable agronomic traits from both parental lines. In this study, the relationship between phenotypic characteristics and the known functional genes of Quan 9311A were analyzed using the rice genome navigation technology based on whole-genome sequencing. The findings revealed that Quan 9311A harbors multiple superior alleles from both 93-11 and Zhong 9A, providing exceptional agronomic traits that are unavailable in earlier CMS lines. Despite the removal of the fertility restorer gene Rf3 from 93-11, numerous chromosomal segments from 93-11 persist in the Quan 9311A genome. Furthermore, the hybrid rice Quanyousimiao (QYSM) and the restorer line Wushansimiao (WSSM) were used as examples to illustrate the important role of Quan 9311A as the female parent in heterosis. It was found that QYSM carries a great number of superior alleles, which accounts for its high grain yield and wide adaptability. These insights not only advanced the utilization of hybrid rice pairing groups but also provided guidance for future breeding endeavors. The study introduced innovative concepts to further integrate genomics with traditional breeding techniques. Ultimately, Quan 9311A signified a significant milestone in rice breeding technology, opening up novel avenues for hybrid rice development.

Biodegradable bone grafts have gained considerable attention in the field of clinical research as they can be used to avoid re-surgery to remove scaffolds. We fabricated biodegradable composite ceramic scaffolds using magnesium oxide and calcium phosphate following the vat photopolymerization technology. We studied the effects of different magnesium oxide content on the process of in vitro degradation of the composite scaffolds and discussed the degradation process by comparing the extent of degradation realized in Tris-HCl buffer and simulated body fluids. We also explored the variations in the mechanical properties of the scaffolds during degradation. The results revealed that the composite scaffolds maintained the strength standard for spongy bone (compressive strength σ: 2–20 MPa) even after 28 d of degradation. Additionally, the strength of the composite scaffold containing 80 wt% magnesium oxide was comparable to the strength standard recommended for cortical bones (σ: 100–200 MPa). Controllable degradation rates were recorded, and acceptable mechanical properties were observed for these scaffolds during degradation. The results reported herein can be potentially used to expand the application prospects of biodegradable scaffolds.

Background: The target definition of consolidation radiotherapy (RT) for extensive stage small-cell lung cancer (ES-SCLC) has not been standardized. This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC. Methods: All ES-SCLC patients without initial brain metastases who completed ≥ 4 cycles of systemic therapy at Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study. We correlated the site of first recurrence to the post-chemotherapy-based radiation volume (small-field). Relapse pattern, progression-free survival (PFS) and overall survival (OS) were compared between those received and did not receive consolidation RT. Results: A total of 152 patients were followed up for a median of 31.7 months (interquartile range [IQR], 23.9–39.6 months). The median PFS and OS of the cohort were 8.3 months (IQR, 6.1–11.2 months) and 16.2 months (IQR, 9.9–24.9 months), respectively. Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort, but also significantly prolonged OS in the subgroup without synchronous liver metastases. Small-field consolidation RT markedly reduced in-field recurrences (hazard ratio [HR], 0.28 [95% CI, 0.12–0.38]; P < 0.001) without increasing out-of-field recurrences (HR, 0.40 [95% CI, 0.13–1.16]; P = 0.080). No relapse was observed at the margin of the targets. Treatment-related toxicities were moderate, with grade 3 acute radiation pneumonia, radiation esophagitis, and bone marrow suppression rates of 8.3%, 3.1%, and 12.5%, respectively. No grade 5 toxicity occurred. Conclusion: Small-field consolidation RT based on post-chemotherapy volume is safe and can significantly improve local control in ES-SCLC.

Introduction: Odorant-binding proteins (OBPs) are a class of small molecular weight soluble proteins that exist as expanded gene families in all insects, acting as ligand carriers mediating olfaction and other physiological processes. During fungal infection, a subset of insect OBPs were shown to be differentially expressed. Objectives: We tested whether the altered expression of insect OBPs during pathogenic infection plays a role in behavioral or immune interactions between insect hosts and their pathogens. Methods: A wide range of techniques including RNAi-directed knockdown, heterologous protein expression, electrophysiological/behavioral analyses, transcriptomics, gut microbiome analyses, coupled with tandem mass spectrometry ion monitoring, were used to characterize the function of a locust OBP in host behavioral and immune responses. Results: The entomopathogenic fungus Metarhizium anisopliae produces the volatile compound phenylethyl alcohol (PEA) that causes behavioral avoidance in locusts. This is mediated by the locust odorant binding protein 11 (LmOBP11). Expression of LmOBP11 is induced by M. anisopliae infection and PEA treatment. LmOBP11 participates in insect detection of the fungal-produced PEA and avoidance of PEA-contaminated food, but the upregulation of LmOBP11 upon M. anisopliae infection negatively affects the insect immune responses to ultimately benefit successful mycosis by the pathogen. RNAi knockdown of LmOBP11 increases the production of antimicrobial peptides and enhances locust resistance to M. anisopliae infection, while reducing host antennal electrophysiological responses to PEA and locust avoidance of PEA treated food. Also, transcriptomic and gut microbiome analyses reveal microbiome dysbiosis and changes in host genes involved in behavior and immunity. These results are consistent with the elevated expression of LmOBP11 leading to enhanced volatile detection and suppression of immune responses. Conclusion: These findings suggest a crosstalk between olfaction and immunity, indicating manipulation of host OBPs as a novel target exploited by fungal pathogens to alter immune activation and thus promote the successful infection of the host.

Sparassis crispa, an edible mushroom, has been reported to show many kinds of physiological functions. The present paper focused on reducing body weight, subcutaneous fat, and visceral fat gain in ovariectomized (OVX) mice. Using the fruiting body powder of the indoor cultivation S. crispa (IT S. crispa: ITSc), one week after the OVX, ITSc was administered to two OVX groups by per os (p.o). In the sham group, 10 mL/kg water and 10 mL/kg saline were administered by p.o. and subcutaneous adm, respectively. OVX groups were divided into four groups. These treatments were performed on animals 6 days a week for 8 weeks. Subcutaneous and visceral fat measurements were performed under inhalation anesthesia with isoflurane using a Latheta LCT-200 X-ray CT system. The biochemical markers and the mRNA expression levels of the PPARγ, adiponectin, TNF-α, PPARα, and leptin were measured. Significant increases in body weight, fat ratio, and glucose levels were detected in OVX mice compared to sham mice. These increases were significantly blocked by ITSc, but not estradiol. Furthermore, ITSc treatment significantly increased adiponectin and leptin levels in adipose tissue. These results suggest that ITSc improves lipid abnormalities due to the less activity of women's ovary function, excluding estrogen functions.

Summary: The role of Epstein-Barr virus (EBV) in lymphoma cells of nodular sclerosis classic Hodgkin lymphoma (NScHL) is controversial. Our aim was to explore this and establish a clinically feasible model for risk stratification. We interrogated data from 542 consecutive subjects with NScHL receiving ABVD therapy and demonstrated EBV-infection in their lymphoma cells with EBV-encoded small RNAs (EBERs) in situ hybridization. Subjects were divided into training and validation datasets. As data from the training dataset suggested EBERs-positivity was the only independent prognostic factor for both progression-free survival (PFS) and overall survival (OS), we developed corresponding prognostic models based on it. Our models showed excellent performance in both training and validation cohort. These data indicate the close association of EBV infection and the outcomes of persons with NScHL receiving ABVD. Additionally, our newly developed models should help physicians estimate prognosis and select individualized therapy.

The fatigue crack initiation and propagation in Nb–Ti micro-alloyed 500 MPa grade steels that usually be used in the automobile beam were investigated. Reducing the content of C and Mn elements based on the reference steel and adding microalloying elements Nb and Ti to obtain the modified steel. The fatigue strengths of the reference steel and the modified steel are 201 MPa and 225 MPa, respectively. Fatigue cracks in the experimental steel were initiated at surface defects and persistent slip bands (PSBs). The modified steel is more susceptible to initiating cracks at the PSBs than the reference steel. There were three kinds of fracture modes in the experimental steels, which were determined by the competition between carbide and inclusion. As the loading stress and the stress intensity factor (Δk) increase, the fracture mode transforms from cleavage (brittle) to dimple (ductile) fracture. Under the circumstance of low loading stress and low Δk, the fracture mode is dominated by the carbide-induced cleavage fracture mechanism. Under the situation of high loading stress and Δk, the fracture mode is dominated by the inclusion-induced dimple fracture mechanism. In addition, the mixed cleavage-dimple region is formed when the two fracture mechanisms compete in the steel.

Nitrate (NO3–) and ammonium (NH4+) are two main inorganic nitrogen (N) sources during crop growth. Here, we enhanced the expression of OsAMT1.1, which encodes a NH4+ transporter, using the NO3–-inducible promoter of OsNAR2.1 and an ubiquitin promoter in transgenic rice plants. Under field condition of 120 kg /hm2 N, agronomic N use efficiency, N recovery efficiency and N transport efficiency, and grain yield of the pOsNAR2.1:OsAMT1.1 transgenic lines were increased compared with those of the wild type (WT) and the pUbi:OsAMT1.1 transgenic plants. Under 2.0 mmol/L NO3– + 0.5 mmol/L NH4+ and 0.5 mmol/L NO3– + 2.0 mmol/L NH4+ conditions of hydroponic culture, compared with the WT, both biomass and total N content were increased in the pOsNAR2.1:OsAMT1.1 transgenic lines. However, biomass was significantly reduced in pUbi:OsAMT1.1 transgenic plants under 0.5 mmol/L NO3– + 2.0 mmol/L NH4+ condition. The lines expressing pOsNAR2.1:OsAMT1.1 exhibited increased OsAMT1.1 expression and 15NH4+ influx in roots under both 2.0 mmol/L NO3– + 0.5 mmol/L NH4+ and 0.5 mmol/L NO3– + 2.0 mmol/L NH4+ conditions. Our study showed that expression of OsAMT1.1 can be promoted when driven by the OsNAR2.1 promoter, especially under high-level nitrate condition, leading to enhancement of NH4+ uptake, N use efficiency and grain yield.

As a neurological disorder in the brain, epilepsy is not only associated with abnormal synchronized discharging of neurons, but also inseparable from non-neuronal elements in the altered microenvironment. Anti-epileptic drugs (AEDs) merely focusing on neuronal circuits frequently turn out deficient, which is necessitating comprehensive strategies of medications to cover over-exciting neurons, activated glial cells, oxidative stress and chronic inflammation synchronously. Therefore, we would report the design of a polymeric micelle drug delivery system that was functioned with brain targeting and cerebral microenvironment modulation. In brief, reactive oxygen species (ROS)-sensitive phenylboronic ester was conjugated with poly-ethylene glycol (PEG) to form amphiphilic copolymers. Additionally, dehydroascorbic acid (DHAA), an analogue of glucose, was applied to target glucose transporter 1 (GLUT1) and facilitate micelle penetration across the blood‒brain barrier (BBB). A classic hydrophobic AED, lamotrigine (LTG), was encapsulated in the micelles via self-assembly. When administrated and transferred across the BBB, ROS-scavenging polymers were expected to integrate anti-oxidation, anti-inflammation and neuro-electric modulation into one strategy. Moreover, micelles would alter LTG distribution in vivo with improved efficacy. Overall, the combined anti-epileptic therapy might provide effective opinions on how to maximize neuroprotection during early epileptogenesis.