MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects.

Regenerative stem cell-like memory (TSCM) CD8+ T cells persist longer and produce stronger effector functions. We found that MEK1/2 inhibition (MEKi) induces TSCM that have naive phenotype with self-renewability, enhanced multipotency and proliferative capacity. This is achieved by delaying cell division and enhancing mitochondrial biogenesis and fatty acid oxidation, without affecting T cell receptor-mediated activation. DNA methylation profiling revealed that MEKi-induced TSCM cells exhibited plasticity and loci-specific profiles similar to bona fide TSCM isolated from healthy donors, with intermediate characteristics compared to naive and central memory T cells. Ex vivo, antigenic rechallenge of MEKi-treated CD8+ T cells showed stronger recall responses. This strategy generated T cells with higher efficacy for adoptive cell therapy. Moreover, MEKi treatment of tumor-bearing mice also showed strong immune-mediated antitumor effects. In conclusion, we show that MEKi leads to CD8+ T cell reprogramming into TSCM that acts as a reservoir for effector T cells with potent therapeutic characteristics.

Identification of Hub Genes and Pathways of Middle Cerebral Artery Occlusion in Aged Rats Using the Gene Expression Omnibus Database.

Stroke remained the leading cause of disability in the world, and the most important non-modifiable risk factor was age. The treatment of stroke for elder patients faced multiple difficulties due to its complicated pathogenesis and mechanism. Therefore, we aimed to identify the potential differentially expressed genes (DEGs) and singnalling pathways for aged people of stroke. To compare the DEGs in the aged rats with or without middle cerebral artery occlusion (MCAO) and to analyse the important genes and the key signaling pathways involved in the development of cerebral ischaemia in aged rats. The Gene Expression Omnibus (GEO) analysis tool was used to analyse the DEGs in the GSE166162 dataset of aged MCAO rats compared with aged sham rats. Differential expression analysis was performed in aged MCAO rats and sham rats using limma. In addition, the 74 DEGs (such as Fam111a, Lcn2, Spp1, Lgals3 and Gpnmb were up-regulated; Egr2, Nr4a3, Arc, Klf4 and Nr4a1 were down-regulated) and potential compounds corresponding to the top 20 core genes in the Protein-Protein Interaction (PPI) network was constructed using the STRING database (version 12.0). Among these 30 compounds, resveratrol, cannabidiol, honokiol, fucoxanthin, oleandrin and tyrosol were significantly enriched. These DEGs were subjected to Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the most significantly enriched pathway in aged MCAO rats. Moreover, innate immune response, the complement and coagulation cascades signaling pathway, the IL-17 and other signaling pathways were significantly correlated with the aged MCAO rats. Our study indicates that multiple genes and pathological processes involved in the aged people of stroke. The immune response might be the key pathway in the intervention of cerebral infarction in aged people.

Ionic Liquid Modified Polymer Intermediate Layer for Improved Charge Extraction toward Efficient and Stable Perovskite/Silicon Tandem Solar Cells.

Monolithic perovskite/silicon tandem solar cells have been attracted much attention in recent years. Despite their high performances, the stability issue of perovskite-based devices is recognized as one of the key challenges to realize industrial application. When comes to the perovskite top subcell, the interface between perovskite and electron transporting layers (usually C60) significantly affects the device efficiency as well as the stability due to their poor adhesion. Here, different from the conventional interfacial passivation using metal fluorides, a hybrid intermediate layer is proposed-PMMA functionalized with ionic liquid (IL)-is introduced at the perovskite/C60 interface. The application of PMMA essentially improves the interfacial stability due to its strong hydrophobicity, while adding IL relieves the charge accumulation between PMMA and the perovskite. Thus, an optimal wide-bandgap perovskite solar cells achieves power conversion efficiency of 20.62%. These cells are further integrated as top subcells with silicon bottom cells in a monolithic tandem structure, presenting an optimized PCE up to 27.51%. More importantly, such monolithic perovskite/silicon cells exhibit superior stability by maintaining 90% of initial efficiency after 1200 h under continuous illumination.

Association of metabolic syndrome severity with frailty progression among Chinese middle and old-aged adults: a longitudinal study.

BACKGROUND: The binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China. METHOD: Participants from the 2011-2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations. RESULTS: A higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(ß per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(ß = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models. CONCLUSIONS: Our findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.

The Role of m6A-Mediated DNA Damage Repair in Tumor Development and Chemoradiotherapy Resistance.

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.

Intrathecal delivery of AAV-NDNF ameliorates disease progression of ALS mice.

Amyotrophic lateral sclerosis (ALS) is a uniformly lethal neurodegenerative disease characterized by progressive deterioration of motor neurons and neuromuscular denervation. Adeno-associated virus (AAV)-mediated delivery of trophic factors is being considered as a potential disease-modifying therapeutic avenue. Here we show a marked effect of AAV-mediated over-expression of neuron-derived neurotrophic factor (NDNF) on SOD1G93A ALS model mice. First, we adopt AAV-PHP.eB capsid to enable widespread expression of target proteins in the brain and spinal cord when delivered intrathecally. Then we tested the effects of AAV-NDNF on SOD1G93A mice at different stages of disease. Interestingly, AAV-NDNF markedly improved motor performance and alleviated weight loss when delivered at early post-symptomatic stage. Injection in the middle post-symptomatic stages still improved the locomotion ability, although it did not alleviate the loss of body weight. Injection in the late stage also extended the life span of SOD1G93A mice. Furthermore, NDNF expression promoted the survival of spinal motoneurons, reduced abnormal protein aggregation, and preserved the innervated neuromuscular functions. We further analyzed the signaling pathways of NDNF expression and found that it activates cell survival and growth-associated mammalian target of rapamycin signaling pathway and downregulates apoptosis-related pathways. Thus, intrathecally AAV-NDNF delivery has provided a potential strategy for the treatment of ALS.

A multifactorial screening model based on the Graves ophthalmopathy quality of life scores in dysthyroid optic neuropathy.

PURPOSE: To validate the Graves ophthalmopathy quality of life (GO-QOL) questionnaire in screening DON and to construct an effective model. METHODS: A total of 194 GO patients were recruited and divided into DON and non-DON (mild and moderate-to-severe) groups. Eye examinations were performed, and quality of life was assessed by the GO-QOL questionnaire. The random forest, decision tree model, receiver operator characteristic (ROC) curve, accuracy and Brier score were determined by R software. RESULTS: In GO-QOL, age, best corrected visual acuity (BCVA), exophthalmos, CAS, severity, and Gorman score were found to be factors related to visual function scores. On the appearance scale, gender, duration of GO, BCVA, exophthalmos, CAS and severity of GO were relevant. Both the visual function scores and appearance scores were significantly lower in DON groups than in non-DON groups (33.18 ± 24.54 versus 81.26 ± 17.39, 60.08 ± 24.82 versus 76.14 ± 27.56). The sensitivity, specificity, and AUC of the visual function scores were 91.1%, 81.7% and 0.939, respectively Visual function scores were used to construct a decision tree model. The sensitivity, specificity, and AUC of the model were 92.9%, 88.0% and 0.941, respectively, with an accuracy of 89.7% and a Brier score of 0.024. CONCLUSIONS: Visual function scores were qualified as a screening method for DON, with a cutoff point of 58. A multifactorial screening model based on visual function scores was constructed.

Benefits of Virtual Reality Training for Cardiopulmonary Resuscitation Skill Acquisition and Maintenance.

OBJECTIVES: To investigate the benefits of virtual reality (VR) first-aid training in acquiring cardiopulmonary resuscitation (CPR) skills. METHODS: A total of 100 non-medical professional volunteers from Nanchang were selected in March 2021 using the convenience sampling method. They were randomly divided into two groups: the VR training group (VR group) and the traditional simulation scenario training group (traditional group). The VR Group underwent immersive virtual reality CPR training with interactive feedback, while the Traditional Group received standard simulation-based CPR training using mannequins and instructor guidance. After training, relevant data were collected for comparative analysis. RESULTS: The study revealed that the VR group consistently outperforming the traditional group in theoretical knowledge test (cardiac arrest recognition, chest compressions, airway management, and artificial respiration) scores at 1, 3, 6, and 12 months post-training (p < 0.05). Similarly, the VR group showed superior performance in overall skills test scores and individual CPR quality metrics at all post-training assessments. The VR group scored higher in total skills, assessment, post-resuscitation assessment, chest compressions (at 1, 3, and 6 months), airway opening, and artificial respiration compared to the traditional group (p < 0.05). Despite these findings, both groups exhibited a gradual decrease in skills test scores over time. CONCLUSIONS: Virtual reality training can significantly improve non-medical professional volunteers' CPR knowledge and skill levels, helping them master and maintain these competencies. However, a decrease in CPR knowledge and skills among the participants over time was observed after VR training, suggesting the need for further retraining sessions.

Association of systemic immunity-inflammation index with metabolic syndrome in U.S. adult: a cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a pathological condition characterized by the abnormal clustering of several metabolic components and has become a major public health concern. We aim to investigate the potential link of Systemic immunity-inflammation index (SII) on MetS and its components. METHODS AND RESULT: Weighted multivariable logistic regression was conducted to assess the relationship between SII and MetS and its components. Restricted cubic spline (RCS) model and threshold effect analysis were also performed. A total of 6,999 U.S. adults were enrolled. Multivariate model found that SII were positively associated with MetS (OR = 1.18;95CI%:1.07-1.30) and hypertension (OR = 1.22; 95CI%:1.12-1.34) in a dose-dependent manner. When SII was converted into a categorical variable, the risk of MetS increased by 36% and the risk of hypertension increased by 53% in the highest quantile of SIIs. The RCS model confirmed linear associations between SII and MetS, as well as a non-linear association between SII and certain components of MetS, including hypertension, hyperglycemia, low HDL, and hyperlipidemia. Meanwhile, the relationship between SII and hypertension presents a J-shaped curve with a threshold of 8.27, above which the risk of hypertension increases. Furthermore, in MetS and hypertension, age, sex, body mass index (BMI), and race were not significantly associated with this positive association based on subgroup analyses and interaction tests(p for interaction > 0.05). CONCLUSIONS: The present study indicated that there was a higher SII association with an increased risk of MetS and hypertension in adults. However, further prospective cohort studies are required to establish a causal relationship between SII and MetS, as well as its components.

Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

Potassium transporter OsHAK9 regulates seed germination under salt stress by preventing gibberellin degradation through mediating OsGA2ox7 in rice.

Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K+ efflux in salt-exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.

TaBln1, a member of the Blufensin family, negatively regulates wheat resistance to stripe rust by reducing Ca2+ influx.

Blufensin1 (Bln1) has been identified as a susceptibility factor of basal defense mechanisms which is unique to the cereal grain crops barley (Hordeum vulgare), wheat (Triticum aestivum), rice (Oryza sativa), and rye (Secale cereale). However, the molecular mechanisms through which Bln1 regulates the wheat immune response are poorly understood. In this study, we found that TaBln1 was significantly induced by Puccinia striiformis f. sp. tritici (Pst) virulent race CYR31 infection. Knockdown of TaBln1 expression by virus-induced gene silencing reduced Pst growth and development, and enhanced the host defense response. In addition, TaBln1 was found to physically interact with a calmodulin, TaCaM3, on the plasma membrane. Silencing TaCaM3 with virus-induced gene silencing increased fungal infection areas and sporulation and reduced wheat resistance to the Pst avirulent race CYR23 (incompatible interaction) and virulent race CYR31 (compatible interaction). Moreover, we found that the accumulation of TaCaM3 transcripts could be induced by treatment with chitin but not flg22. Silencing TaCaM3 decreased the calcium (Ca2+) influx induced by chitin, but silencing TaBln1 increased the Ca2+ influx in vivo using a noninvasive micro-test technique. Taken together, we identified the wheat susceptibility factor TaBln1, which interacts with TaCaM3 to impair Ca2+ influx and inhibit plant defenses.

Porphyrin conjugated polymer/Pt-loaded graphite carbon nitride nanocomposites for efficient charge separation and broadband responsive H2evolution.

An efficient broadband responsive two-dimensional (2D) heterometallic Zn-/Co-porphyrin conjugated polymer (ZnCoP-F CP) with its Co-porphyrin bridging unit bearing two perfluorophenyls is coupled with 2.0 wt% Pt-loaded graphite carbon nitride (PCN) to fabricate a novel 2D/2D nanocomposite (ZnCoP-F/PCN). The resultant ZnCoP-F/PCN composite with an optimal mass ratio exhibits broadband (UV-vis-NIR) responsive H2evolution reaction (HER) activity up to 432µmol h-1, 5.2 and 2.8 times higher than that of the ZnCoP-F CP (83µmol h-1) and PCN (151µmol h-1) alone, respectively. Furthermore, the ZnCoP-F/PCN displays excellent apparent quantum yields (AQY) of 18.2%, 18.3%, 17.6%, 16.5%, 13.9%, 8.7%, 5.1%, 4.3%, 1.9%, 0.95% and 0.62% at 350, 380, 420, 450, 500, 550, 600, 700, 785, 850 and 950 nm, which are also higher than that of ZnCoP-F CP illuminated at the respective monochromatic light. The enhanced broadband responsive HER performance of ZnCoP-F/PCN can be attributed to the easily assembled ZnCoP-F CP and PCN nanosheets through strongπ-πstacking interaction, which can facilitate the fast charge transfer from ZnCoP-F CP to PCN for HER. This work opens a new pathway to fabricate porphyrin polymer-based nanocomposite for more efficiently converting solar radiation and water into H2.

Enhanced removal organic compounds and particles from cooking fume using activated sludge scrubber filled loofah: From performance to the mechanism.

The catering industry's growth has resulted in cooking fume pollution becoming a major concern in people's lives. As a result, its removal has become a core research focus. Natural loofah is an ideal biofilm carrier, providing a conducive environment for microorganisms to grow. This study utilized natural loofah to fill domesticated activated sludge in a bioscrubber, forming biofilms that enhance the ability to purify cooking fume. This study found that the biomass of loofah biofilms per gram is 104.56 mg. The research also determined the removal efficiencies for oils, Non-methane total hydrocarbons (NMHC), PM2.5, and PM10 from cooking fumes, which were 91.53%, 67.53%, 75.25%, and 82.23%, respectively. The maximum elimination capacity for cooking fumes was found to be 20.7 g/(m3·h). Additionally, the study determined the kinetic parameters for the biodegradation of oils (Kc and Vmax) to be 4.69 mg L-1 and 0.026 h-1, respectively, while the enzyme activities of lipase and catalase stabilized at 75.50 U/mgprots and 67.95 U/mgprots. The microbial consortium identified in the biofilms belonged to the phylum Proteobacteria and consisted mainly of Sphingomonas, Mycobacterium, and Lactobacillus, among others.

Contribution of calcium dysregulation to impaired coronary artery contraction in Zucker diabetic fatty rats.

Diabetic coronary artery injury is closely associated with Ca2+ dysregulation, although the underlying mechanism remains unclear. This study explored the role and mechanism of Ca2+ handling in coronary artery dysfunction in type 2 diabetic rats. Zucker diabetic fatty (ZDF) rats were used as the type 2 diabetes mellitus model. The contractility of coronary artery rings induced by KCl, CaCl2 , 5-HT and U46619 was significantly lower in ZDF rats than in Zucker lean rats. Vasoconstriction induced by 5-HT and U46619 was greatly inhibited by nifedipine. However, in the presence of 1 µM nifedipine or in the Ca2+ -free KH solution containing 1 µM nifedipine, there was no difference in the vasoconstriction between Zucker lean and ZDF rats. Store-operated calcium channels (SOCs) were not involved in coronary vasoconstriction. The downregulation of contractile proteins and the upregulation of synthesized proteins were in coronary artery smooth muscle cells (CASMCs) from ZDF rats. Metformin reversed the reduction of vasoconstriction in ZDF rats. Taken together, L-type calcium channel is important for regulating the excitation-contraction coupling of VSMCs in coronary arteries, and dysregulation of this channel contributes to the decreased contractility of coronary arteries in T2DM.

A diagnostic model based on color vision examination for dysthyroid optic neuropathy using Hardy-Rand-Rittler color plates.

PURPOSE: To investigate color vision deficiency and the value of Hardy-Rand-Rittler (HRR) color plates in monitoring dysthyroid optic neuropathy (DON) to improve the diagnosis of DON. METHODS: The participants were divided into DON and non-DON (mild and moderate-to-severe) groups. All the subjects underwent HRR color examination and comprehensive ophthalmic examinations. The random forest and decision tree models based on the HRR score were constructed by R software. The ROC curve and accuracy of different models in diagnosing DON were calculated and compared. RESULTS: Thirty DON patients (57 eyes) and sixty non-DON patients (120 eyes) were enrolled. The HRR score was lower in DON patients than in non-DON patients (12.1 ± 6.2 versus 18.7 ± 1.8, p < 0.001). The major color deficiency was red-green deficiency in DON using HRR test. The HRR score, CAS, RNFL, and AP100 were found to be important factors in predicting DON from random forest and selected by decision tree to construct the multifactor model. The sensitivity, specificity, and the area under the curve (AUC) of the HRR score were 86%, 72%, and 0.87, respectively. The HRR score decision tree had a sensitivity, specificity, and AUC of 93%, 57%, and 0.75, respectively, with an accuracy of 82%. The data of the multifactor decision tree were 90%, 89%, and 0.93 for sensitivity, specificity, and AUC, respectively, with an accuracy of 91%. CONCLUSION: The HRR test was valid as screening method for DON. The multifactor decision tree based on the HRR test improved the diagnostic efficacy for DON. An HRR score of less than 12 and red-green deficiency may be characteristic of DON.

Identification and characterization of a heme exporter from the MRP family in Drosophila melanogaster.

BACKGROUND: The heme group constitutes a major functional form of iron, which plays vital roles in various biological processes including oxygen transport and mitochondrial respiration. Heme is an essential nutrient, but its pro-oxidant nature may have toxic cellular effects if present at high levels, and its synthesis is therefore tightly regulated. Deficiency and excess of heme both lead to pathological processes; however, our current understanding of metazoan heme transport is largely limited to work in mammals and the worm Caenorhabditis elegans, while functional analyses of heme transport in the genetically amenable Drosophila melanogaster and other arthropods have not been explored. RESULTS: We implemented a functional screening in Schneider 2 (S2) cells to identify putative heme transporters of D. melanogaster. A few multidrug resistance-associated protein (MRP) members were found to be induced by hemin and/or involved in heme export. Between the two plasma membrane-resident heme exporters CG4562 and CG7627, the former is responsible for heme transit across the intestinal epithelium. CG4562 knockdown resulted in heme accumulation in the intestine and lethality that could be alleviated by heme synthesis inhibition, human MRP5 (hMRP5) expression, heme oxygenase (HO) expression, or zinc supplement. CG4562 is mainly expressed in the gastric caeca and the anterior part of the midgut, suggesting this is the major site of heme absorption. It thus appears that CG4562 is the functional counterpart of mammalian MRP5. Mutation analyses in the transmembrane and nucleotide binding domains of CG4562 characterized some potential binding sites and conservative ATP binding pockets for the heme transport process. Furthermore, some homologs in Aedes aegypti, including that of CG4562, have also been characterized as heme exporters. CONCLUSIONS: Together, our findings suggest a conserved heme homeostasis mechanism within insects, and between insects and mammals. We propose the fly model may be a good complement to the existing platforms of heme studies.

Deep Reinforcement Learning for Charging Scheduling of Electric Vehicles Considering Distribution Network Voltage Stability.

The rapid development of electric vehicle (EV) technology and the consequent charging demand have brought challenges to the stable operation of distribution networks (DNs). The problem of the collaborative optimization of the charging scheduling of EVs and voltage control of the DN is intractable because the uncertainties of both EVs and the DN need to be considered. In this paper, we propose a deep reinforcement learning (DRL) approach to coordinate EV charging scheduling and distribution network voltage control. The DRL-based strategy contains two layers, the upper layer aims to reduce the operating costs of power generation of distributed generators and power consumption of EVs, and the lower layer controls the Volt/Var devices to maintain the voltage stability of the distribution network. We model the coordinate EV charging scheduling and voltage control problem in the distribution network as a Markov decision process (MDP). The model considers uncertainties of charging process caused by the charging behavior of EV users, as well as the uncertainty of uncontrollable load, system dynamic electricity price and renewable energy generation. Since the model has a dynamic state space and mixed action outputs, a framework of deep deterministic policy gradient (DDPG) is adopted to train the two-layer agent and the policy network is designed to output discrete and continuous control actions. Simulation and numerical results on the IEEE-33 bus test system demonstrate the effectiveness of the proposed method in collaborative EV charging scheduling and distribution network voltage stabilization.

Dissolved organic matter evolution can reflect the maturity of compost: Insight into common composting technology and material composition.

Dissolved organic matter (DOM) can clearly reflect composting components changes, thus it is supposed to indicate the humification process during composting. To demonstrate this, three compost mixtures and two techniques were arranged. DOM evolution was detected by three spectral techniques. X-ray diffraction (XRD) showed that the crystal structure substances decreased gradually during the composting, including cellulose, struvite, sylvine, quartz, and calcite; Specifically, the struvite was found, which was conducive to the fixation of nitrogen and phosphorus. Fourier transform infrared spectroscopy (FTIR) and three-dimensional fluorescence spectroscopy (3D-EEM) further showed that pig manure-based mixtures, added cabbage, and windrow composting are beneficial to sugar, protein, fulvic acid, and soluble microbial by-products decompose and humic acids produce. This process was closely related to the change of physical-chemical parameters (temperature; pH; moisture content; and NH4+-N content) and maturity index (C/N ratio, E4/E6 and GI). Therefore, DOM evolution could quickly reflect the maturity process of compost. In subsequent research, the quantitative analysis of DOM components can be considered to modify DOM spectral parameters, or to build a model, so as to achieve rapid evaluation of compost maturity.

Computational-Intelligence-Based Scheduling with Edge Computing in Cyber-Physical Production Systems.

Real-time performance and reliability are two critical indicators in cyber-physical production systems (CPPS). To meet strict requirements in terms of these indicators, it is necessary to solve complex job-shop scheduling problems (JSPs) and reserve considerable redundant resources for unexpected jobs before production. However, traditional job-shop methods are difficult to apply under dynamic conditions due to the uncertain time cost of transmission and computation. Edge computing offers an efficient solution to this issue. By deploying edge servers around the equipment, smart factories can achieve localized decisions based on computational intelligence (CI) methods offloaded from the cloud. Most works on edge computing have studied task offloading and dispatching scheduling based on CI. However, few of the existing methods can be used for behavior-level control due to the corresponding requirements for ultralow latency (10 ms) and ultrahigh reliability (99.9999% in wireless transmission), especially when unexpected computing jobs arise. Therefore, this paper proposes a dynamic resource prediction scheduling (DRPS) method based on CI to achieve real-time localized behavior-level control. The proposed DRPS method primarily focuses on the schedulability of unexpected computing jobs, and its core ideas are (1) to predict job arrival times based on a backpropagation neural network and (2) to perform real-time migration in the form of human-computer interaction based on the results of resource analysis. An experimental comparison with existing schemes shows that our DRPS method improves the acceptance ratio by 25.9% compared to the earliest deadline first scheme.