Trajectory mapping of the early Drosophila germline reveals controls of zygotic activation and sex differentiation.

Germ cells in Drosophila melanogaster are specified maternally shortly after fertilization and are transcriptionally quiescent until their zygotic genome is activated to sustain further development. To understand the molecular basis of this process, we analyzed the progressing transcriptomes of early male and female germ cells at the single-cell level between germline specification and coalescence with somatic gonadal cells. Our data comprehensively cover zygotic activation in the germline genome, and analyses on genes that exhibit germline-restricted expression reveal that polymerase pausing and differential RNA stability are important mechanisms that establish gene expression differences between the germline and soma. In addition, we observe an immediate bifurcation between the male and female germ cells as zygotic transcription begins. The main difference between the two sexes is an elevation in X Chromosome expression in females relative to males, signifying incomplete dosage compensation, with a few select genes exhibiting even higher expression increases. These indicate that the male program is the default mode in the germline that is driven to female development with a second X Chromosome.

The inappropriate application of imidacloprid destroys the ability of predatory natural enemies to control pests in the food chain: A case study of the feeding behavior of Orius similis on Frankliniella occidentalis.

Insecticides are an indispensable and important tool for agricultural production. However, the inappropriate application of insecticides can cause damage to the food chain and ecosystem. Orius similis is an important predatory and natural enemy of Frankliniella occidentalis. Imidacloprid is widely used to control pests, but will inevitably exert adverse effects on O. similis. In order to determine the effect of different imidacloprid treatments on the ability of O. similis to prey on the 2nd-instar nymphs of F. occidentalis, we determined the toxicity and predation of imidacloprid on different stages of O. similis under contact and ingestion treatments. In addition, we used the Holling disc equation to evaluate the ability of O. similis to search and exhibit predatory activity following contact and ingestion treatments. Analysis showed that the highest LC10 and LC20 values for imidacloprid contact and ingestion toxicity treatment were 17.06 mg/L and 23.74 mg/L, respectively. Both imidacloprid treatments led toa reduction in the predatory of O. similis on prey. The functional responses of the 3rd to 5th instar nymphs, along with female and male O. similis adults to the 2nd-instar nymphs of F. occidentalis were consistent with the Holling type II response following contact and ingestion with imidacloprid. However, following imidacloprid treatment, the handing time (Th) of O. similis with single F. occidentalis was prolonged and the instantaneous attack rate (a) was reduced after imidacloprid treatment. The predatory capacity (a/Th) of female O. similis adults when treated with the LC10 concentration of imidacloprid by ingestion was 52.85; this was lower than that of the LC10 concentration of imidacloprid in the contact treatment (57.67). The extent of predation of O. similis on the 2nd-instar nymphs of F. occidentalis was positively correlated with prey density, although the search effect was negatively correlated with prey density. The most extensive search effect was exhibited by adult O. similis females. Simulations with the Hessell-Varley interference model showed that an increase in the number of O. similis would reduce search efficiency regardless of whether they were treated with imidacloprid or not. Thus, O. similis, especially female adults, exhibited strong potential for controlling the 2nd-instar nymphs of F. occidentalis. The toxicity of ingestion following treatment with the same concentration of imidacloprid in O. similis was greater than that of contact treatment. When using O. similis to control F. occidentalis in the field, we should increase the number of female adults released, and prolong the interval between imidacloprid treatment and O. similis exposure. This strategy will improve the control ability of O. similis, coordinate both chemical and biological control, reduce the impact of pesticides on the environment, and improve the efficiency of agricultural production.

Association between allostatic load and depression in patients with sleep disorders: Evidence from national health and nutrition examination survey.

OBJECTIVE: Allostatic load (AL) is an indicator of cumulative wear and tear on the body's physiological systems that can predict the onset of a range of health problems. However, the relationship between AL and depression in patients with sleep disorders remains unclear. This study aimed to explore the association between AL and depression in patients with sleep disorders. METHODS: Using data from the 2015-2016 National Health and Nutrition Examination Survey, a total of 4618 adults aged 18 years and older in the United States were included in this cross-sectional analysis. AL was calculated using nine biological markers, with a score of ≥3 indicating a high level. Depression was assessed using the Patient Health Questionnaire-9, and a score of 10 or higher indicated a potential risk of depression. Logistic regression models were employed to analyze the relationship between AL and depression. RESULTS: Among the 1309 participants diagnosed with sleep disorders, 212 (16.2%) were identified as being at risk of depression. A total of 55.2% (n = 117) of the depressed persons had high AL levels. In the unadjusted model, AL levels were associated with depression in those with sleep disorders (OR:1.53, 95% CI = 1.14-2.05; P < .01). This relationship remained significant in the adjusted model (OR:1.52, 95% CI = 1.11-2.10, P < .05), after controlling for potential confounding factors. CONCLUSION: The findings showed that high AL levels in patients with sleep disorders were positively associated with depression, indicating that elevated AL may increase the risk of depression in this population, or alternatively, depression may increase the risk of AL.

Multiplexing the Quantitation of MAP Kinase Activities Using Differential Sensing.

Protein kinases are therapeutic targets for many human diseases, but the lack of user-friendly quantitative assays limits the ability to follow the activities of numerous kinases at once (multiplexing). To develop such an assay, we report an array of sulfonamido-oxine (SOX)-labeled peptides showing cross-reactivity to different mitogen-activated protein kinases (MAPKs) for use in a differential sensing scheme. We first verified using linear discriminant analysis that the array could differentiate MAPK isoforms. Then, using principal component analysis, the array was optimized based on the discrimination imparted by each SOX-peptide. Next, the activity of individual MAPK families in ternary mixtures was quantified by support vector machine regression. Finally, we multiplexed the quantification of three MAPK families using partial least squares regression in A549 cell lysates, which has possible interference from other kinase classes. Thus, our method simultaneously quantifies the activity of multiple kinases. The technique could be applied to other protein kinase families and the monitoring of diseases.

Effects of electron transport layer thickness on light extraction in corrugated OLEDs.

This study reported the effects of electron transport layer (ETL) thickness on light extraction in corrugated organic light-emitting diodes (OLEDs) and each layer in OLEDs exhibited a periodical corrugated structure, which was determined by depositing thin films on a glass substrate with a nanoimprinted blazed grating structure. The insight is that light extraction in corrugated OLEDs significantly depends on the ETL thickness. Varying the ETL thickness changed the distribution of carrier recombination and led to exciton formation and optical interference, thereby resulting in different attribution of optical loss modes in OLEDs, which increased or even decreased light extraction and device efficiency. Trapped light extraction from the surface plasmon polariton (SPP) and waveguide (WG) modes was identified by splitting the light into transverse electric and transverse magnetic emissions. Thus, the contributions from the individual SPP and WG modes to the external quantum efficiency (EQE) were distinctly clarified by comparing the experimental results with the theoretical calculations. At the ETL thickness of 115 nm, the corrugated OLED exhibited a significantly enhanced (1.83-fold) EQE compared to the planar one due to the effective extraction of trapped light from the SPP and WG modes. The EQE was enhanced by 0.5%, wherein 0.39% came from the WG mode and 0.11% came from the SPP mode.

Direct detection of virus-like particles using color images of plasmonic nanostructures.

We propose a measurement method for sensitive and label-free detections of virus-like particles (VLPs) using color images of nanoplasmonic sensing chips. The nanoplasmonic chip consists of 5×5 gold nanoslit arrays and the gold surface is modified with specific antibodies for spike protein. The resonant wavelength of the 430-nm-period gold nanoslit arrays underwater environment is about 570 nm which falls between the green and red bands of the color CCD. The captured VLPs by the specific antibodies shift the plasmonic resonance of the gold nanoslits. It results in an increased brightness of green pixels and decreased brightness of red pixels. The image contrast signals of (green - red) / (red + green) show good linearity with the surface particle density. The experimental tests show the image contrast method can detect 100-nm polystyrene particles with a surface density smaller than 2 particles/µm2. We demonstrate the application for direct detection of SARS-CoV-2 VLPs using a simple scanner platform. A detection limit smaller than 1 pg/mL with a detection time less than 30 minutes can be achieved.

Seas the day: Co-designing immersive virtual reality exergames with exercise professionals and people living with dementia.

BACKGROUND: Physical activity (PA) is associated with physical and cognitive benefits among people living with dementia or mild cognitive impairment (PLWD/MCI) and is a meaningful activity that can improve their confidence in everyday life. Exercising in virtual reality environments (VR Exergame) is becoming an increasingly feasible and enjoyable way to promote PA and well-being in PLWD/MCI. Although co-design can significantly improve the design of technology, it is rarely done with PLWD/MCI. This study uses participatory design methods and collaborative approaches to involve key stakeholders to develop and test a VR Exergame "Seas the Day", a novel solution targeting PLWD/MCI well-being. METHODS: A multi-stage, user-centered co-design approach was used to custom-build VR Exergames tailored to the unique needs and abilities of PLWD/MCI based on a first generation of the prototype that was previously developed and tested with PLWD/MCI. This paper describes the next iteration of the prototype. Processes included concept ideation and brainstorming activities, iterative prototyping, and playtesting/input/feedback sessions with key stakeholders (PLWD/MCI, exercise professionals, engineers, VR game designers, content developers). RESULTS: The multidisciplinary and collaborative design process occurred over 15 months (overlapping with COVID-19 pandemic) with 7 PLWD/MCI (6 females; M=81.3 years) and 9 exercise professionals (7 females; M=38.1 years) to date. The game was designed to target movements identified by exercise professionals and researchers (aerobic exercises, range of motion, seated-balance, quick response to stimuli) and is structured in three exercise stages (warm-up, conditioning, cool-down). To ensure safety of participants while using VR headsets, only seated upper-limb exercises were targeted. Stakeholder feedback regarding game mechanics, aesthetics, and visual/auditory cues were gathered during brainstorming and playtesting sessions and implemented into specific game-related scenarios (tai-chi, rowing, fishing). CONCLUSION: We presented the process, outcomes, and challenges of adopting a participatory/collaborative approach with multiple stakeholder groups to co-design VR Exergames tailored to PLWD/MCI. Next steps will include a mixed-method evaluation of the VR Exergames among community-dwelling older adults and PLWD/MCI in retirement communities and long-term care to evaluate: i) feasibility and acceptability of use, ii) game user experience, iii) barriers/facilitators to uptake of VR Exergames; and iv) inform/validate VR Exergames gameplay metrics reflective of cognitive and motor performance.

Lysergic acid diethylamide causes mouse retinal damage by up-regulating p-JAK1/p-STAT1.

Purpose: Lysergic acid diethylamide (LSD) is a powerful hallucinogen with high potential for abuse. There is far less known about its effects on the retina, especially the underlying mechanisms. This study was to investigate the acute toxicity of LSD on the retina of C57 mice and its mechanisms of action.Methods: C57 mice were treated with LSD at progressively increasing doses (0.2-1.2 mg/kg) intraperitoneally two times daily for 5 days, mice treated with saline served as negative control. Electroretinography (ERG) was used to test the function of the retina. Toluidine blue staining was used to detect the morphology of the retina. Enzyme-linked immunosorbent assay (ELISA) was used to measure the apoptosis-related factors. Real-time PCR and western blot techniques were used to measure expression changes of genes and proteins, respectively.Results: LSD treatment caused retinal damage, as shown by a decrease in ERG response and the loss of photoreceptor cells. LSD treatment also increased apoptosis through up-regulating the expression of p-JAK1/p-STAT1.Conclusions: Our study indicated that intraperitoneal administration of LSD-induced retinal damage of C57 mice, at least partially through regulating the JAK/STAT pathway.

Polymer LEDs with improved efficacy via periodic nanostructure-based aluminum.

Periodic aluminum-capped nanoslit arrays were produced on a polycarbonate plastic substrate by rapid hot embossing nanoimprint lithography and thermal evaporation, and they were used as a transparent window for blue-emitting polymer light-emitting diodes (PLEDs). The external quantum efficiency of blue-emitting PLEDs was enhanced by the surface plasmon polaritons of the periodic aluminum-capped nanoslit arrays. A maximum current efficiency of 4.84 cd/A was achieved for the proposed PLED, which was over 2.2 times that of the reference PLED (2.18 cd/A). These results demonstrate that periodic nanostructure can assist in the simple and low-cost fabrication of high-performance polymer optoelectronic devices.

Efficacy improvement in polymer LEDs via silver-nanoparticle doping in the emissive layer.

The coupling of surface plasmons and excitons in the emissive layer (EML) can improve the performance of polymer light-emitting diodes (PLEDs). Silver nanoparticles (Ag-NPs) with a decahedron structure are prepared by the chemical reduction and photochemical methods and doped directly into the EML after the phase-transfer process. The surface plasmon resonance effect of Ag-NPs, which makes full use of quenched excitons and increases the efficiency of excitons in the EML in a PLED, enhances the current efficacy by a factor of 75 relative to that of the undoped reference device (from 0.22 to 16.64 cd/A). These results demonstrate that Ag-NPs can assist in simple and low-cost fabrication of high-performance polymer optoelectronic devices.

Ratiometric Hg2+ /Ag+ Probes with Orange Red-White-Blue Fluorescence Response Constructed by Integrating Vibration-Induced Emission with an Aggregation-Induced Emission Motif.

Two novel ratiometric fluorometric probes 6 a and 6 b have been designed and synthesized for the detection of Hg2+ and Ag+ , respectively. Each of these probes is comprised of a 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) skeleton, a tetraphenylethylene (TPE) unit, and two thymine/adenine groups. In this proof-of-concept work, the DPAC unit featuring vibration-induced emission (VIE) characteristics serves as a dual-emission chromogen, whereas the TPE moiety, which is noted for its aggregation-induced emission (AIE) properties, functions mainly as a signal amplifier. The coordination between the thymine/adenine groups and Hg2+ /Ag+ leads to the formation of aggregates, which restricts the intramolecular vibrations of DPAC and the intramolecular rotations of TPE, activating the AIE effect of TPE and resulting in the bent form of DPAC. Accordingly, the overall fluorescence changed from moderate orange-red (Iorange-red ) to intense blue light (Iblue ) passing through the white-light region, concurrently with an enhancement of fluorescence at 475 nm and a dramatic increase in the ratio of Iblue /Iorange-red . Furthermore, the superb sensitivity of 6 a/6 b towards Hg2+ /Ag+ has been demonstrated by the detection limit, which is as low as 6.1 nm and 0.1 µm, respectively. Both of these values are below the maximum concentration in drinking water permitted by the U.S. Environmental Protection Agency, demonstrating their great potential to be applied for real-world metal-ion sensing.

Enhanced luminescence efficiency of Ag nanoparticles dispersed on indium tin oxide for polymer light-emitting diodes.

This study presents a substantial enhancement in electroluminescence achieved by depositing Ag nanoparticles on an ITO-coated glass substrate (Ag/ITO) for approximately 10-s to form novel window materials for use in polymer light-emitting diodes (PLEDs). The PLEDs discussed herein are single-layer devices based on a poly[9,9-dioctylfluorene-co-benzothiadiazole] (F8BT) emissive layer. In addition to its low cost, this novel fabrication method can effectively increase the charge transport properties of the active layer to meet the high performance requirements of PLEDs. Due to the increased conductivity and work function of the Ag/ITO substrate, the electroluminescence intensity was increased by nearly 3.3-fold compared with that of the same PLED with a bare ITO substrate.

Dendritic Cell-Derived Exosomes in Cancer Immunotherapy.

Exosomes are nanoscale vesicles released by diverse types of cells for complex intercellular communication. Numerous studies have shown that exosomes can regulate the body's immune response to tumor cells and interfere with the tumor microenvironment (TME). In clinical trials on dendritic cell (DC)-based antitumor vaccines, no satisfactory results have been achieved. However, recent studies suggested that DC-derived exosomes (DEXs) may be superior to DC-based antitumor vaccines in avoiding tumor cell-mediated immunosuppression. DEXs contain multiple DC-derived surface markers that capture tumor-associated antigens (TAAs) and promote immune cell-dependent tumor rejection. These findings indicate the necessity of the further development and improvement of DEX-based cell-free vaccines to complement chemotherapy, radiotherapy, and other immunotherapies. In this review, we highlighted the recent progress of DEXs in cancer immunotherapy, particularly by concentrating on landmark studies and the biological characterization of DEXs, and we summarized their important role in the tumor immune microenvironment (TIME) and clinical application in targeted cancer immunotherapy. This review could enhance comprehension of advances in cancer immunotherapy and contribute to the elucidation of how DEXs regulate the TIME, thereby providing a reference for utilizing DEX-based vaccines in clinical practice.

QTL mapping and analysis for drought tolerance in rice by genome-wide association study.

Rice drought resistance is a complicated quantitative feature involving a range of biological and agronomic variables, but little is known about the underlying genetics and regulatory mechanisms that regulate drought tolerance. This study used 120 recombinant inbred lines (RILs), derived from a cross between drought tolerant Lvhan 1 and susceptible Aixian 1. The RILs were subjected to drought stress at the first ear stage, and phenotypic data of 16 agronomic and physiological traits under varying conditions were investigated. Genome-wide association study (GWAS) on the drought resistance index of traits was carried out. A total of 9 quantitative trait loci (QTLs) associated with drought-related traits were identified on chromosomes 2, 6, 7, 8, 9, and 10, which includes QTLs for plant height (PH) qPH10.1, effective panicles number (EPN) qEPN6.1, panicle length (PL) qPL9.1, thousand-grain weight (TGW) qTGW2.1, qTGW6.1, qTGW8.1, leaf length (LL) qLL7.1, leaf width (LW) qLW7.1, and leaf area (LA) qLA7.1. The fraction of phenotypic variation explained by individual QTL varied from 10.6% to 13.9%. Except for days to flowering (DTF), the mean values of all traits under normal water management conditions were considerably higher than those under drought conditions. Except for the DTF, the drought resistance index of all rice traits was less than 1, indicating that drought treatment reduced the EPN, FGPP, SSR, PH, and LA, which affected the growth and development of rice. The drought resistance index of DTF was 1.02, indicating that drought prolonged the heading time of rice and diminish the yield parameters. Along with identifying QTLs, the results also predicted ten candidate genes, which are directly or indirectly involved in various metabolic functioning related to drought stress. The identification of these genomic sites or QTLs that effectively respond to water scarcity will aid in the quest of understanding the drought tolerance mechanisms. This study will facilitate the marker-assisted rice breeding and handy in the breeding of drought-tolerant rice varieties.

Classification of Alzheimer's disease in MRI images using knowledge distillation framework: an investigation.

PURPOSE: Computer-aided MRI analysis is helpful for early detection of Alzheimer's disease(AD). Recently, 3D convolutional neural networks(CNN) are widely used to analyse MRI images. However, 3D CNN requires huge memory cost. In this paper, we introduce cascaded CNN and long and short-term memory (LSTM) networks. We also use knowledge distillation to improve the accuracy of the model using small medical image dataset. METHODS: We propose a cascade structure, CNN-LSTM. CNN is used as the function of feature extraction, and LSTM is used as the classifier. In this way, the correlation between different slices can be considered and the calculation cost caused by 3D data can be reduced. To overcome the problem of limited image training data, transfer learning is a more reasonable way of feature extraction. We use the knowledge distillation algorithm to improve the performance of student models for AD diagnosis through a powerful teacher model to guide the work of student models. RESULTS: The accuracy of the proposed model is improved using knowledge distillation. The results show that the accuracy of the student models reached 85.96% after the guidance of the teacher models, an increase by 3.83%. CONCLUSION: We propose cascaded CNN-LSTM to classify 3D ADNI data, and use knowledge distillation to improve the model accuracy when trained with small size dataset. It can process 3D data efficiently as well as reduce the computational cost.

A metric learning-based method using graph neural network for pancreatic cystic neoplasm classification from CTs.

PURPOSE: Pancreatic cystic neoplasms (PCNs) are relatively rare neoplasms and difficult to be classified preoperatively. Ordinary deep learning methods have great potential to provide support for doctors in PCNs classification but require a quantity of labeled samples and exact segmentation of neoplasm. The proposed metric learning-based method using graph neural network (GNN) aims to overcome the limitations brought by small and imbalanced dataset and get fast and accurate PCNs classification result from computed tomography (CT) images. METHODS: The proposed framework applies GNN. GNNs perform well in fusing information and modeling relational data and get better results on dataset with small size. Based on metric learning strategy, model learns distance from the data. The similarity-based algorithm enhances the classification performance, and more characteristic information is found. We use a convolutional neural network (CNN) to extract features from given images. Then GNN is used to find the similarity between each two feature vectors and complete the classification. Several subtasks consisting of randomly selected images are established to improve generalization of the model. The experiments are carried out on the dataset provided by Huashan Hospital. The dataset is labeled by postoperative pathological analysis and contains region of interest (ROI) information calibrated by experts. We set two tasks based on the dataset: benign or malignant diagnosis of PCNs and classification of specific types. RESULTS: Our model shows good performance on the two tasks with accuracies of 88.926% and 74.497%. The comparison of different methods' F1 scores in the benign or malignant diagnosis shows that the proposed GNN-based method effectively reduces the negative impact brought by imbalanced dataset, which is also verified by the macroaverage comparison in the four-class classification task. CONCLUSIONS: Compared with existing models, the proposed GNN-based model shows better performance in terms of imbalanced dataset with small size while reducing labeling cost. The result provides a possibility for its application into the computer-aided diagnosis of PCNs.

Combined Antioxidant-Antibiotic Treatment for Effectively Healing Infected Diabetic Wounds Based on Polymer Vesicles.

Infected diabetic wounds are difficult to heal due to high reactive oxygen species (ROS) concentrations and recurrent infections. Such wounds can easily deteriorate into a diabetic ulcer, a chronic diabetic complication with a very high mortality rate. Herein, we propose a combined antioxidant-antibiotic therapy based on poly(ε-caprolactone)-block-poly(glutamic acid) polymer vesicle to treat infected diabetic wounds. This was realized by in situ decoration of stable, well-dispersed ceria nanoparticles onto ciprofloxacin (CIP)-loaded polymer vesicles. These resulting CIP-loaded and ceria-decorated polymer vesicles (CIP-Ceria-PVs) exhibited high superoxide dismutase mimetic activity to inhibit superoxide free radicals (the inhibition rate reached ∼50% at an extremely low cerium concentration of 1.25 µg/mL). When the cerium content is in the range of 5-20 µg/mL, the CIP-Ceria-PVs showed the highest protective capability to normal L02 cells from damage of superoxide free radicals. In addition, the CIP-Ceria-PVs exhibited enhanced antibacterial activity (the dosage of CIP in CIP-Ceria-PVs was reduced by 25-50% compared to free CIP). In vivo treatment of infected diabetic wounds was performed on a diabetic mice model. The CIP-Ceria-PVs could effectively cure infected diabetic wounds within 14 days. Overall, a combined antioxidant-antibiotic therapy was proposed by introducing ceria nanoparticles and CIP into polymer vesicles for the treatment of infected diabetic wounds.

Acetylcholinesterase electrochemical biosensors with graphene-transition metal carbides nanocomposites modified for detection of organophosphate pesticides.

An acetylcholinesterase biosensor modified with graphene and transition metal carbides was prepared to detect organophosphorus pesticides. Cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy were used to characterize the electrochemical catalysis of the biosensor: acetylcholinesterase/chitosan-transition metal carbides/graphene/glassy carbon electrode. With the joint modification of graphene and transition metal carbides, the biosensor has a good performance in detecting dichlorvos with a linear relationship from 11.31 µM to 22.6 nM and the limit of detection was 14.45 nM. Under the premise of parameter optimization, the biosensor showed a good catalytic performance for acetylcholine. Compared to the biosensors without modification, it expressed a better catalytic performance due to the excellent electrical properties, biocompatibility and high specific surface area of graphene, transition metal carbides. Finally, the biosensor exhibits good stability, which can be stored at room temperature for one month without significant performance degradation, and has practical potential for sample testing.

A new strategy for achieving single-molecular white-light emission: using vibration-induced emission (VIE) plus aggregation-induced emission (AIE) mechanisms as a two-pronged approach.

Single-molecular white-light emissions with CIE coordinates of (0.33, 0.37) and (0.33, 0.31) were achieved with DPAC-p-TPE in viscous solution and with DPAC-Tri(o1,2) in the aggregation state through the combination of vibration-induced emission (VIE) and aggregation-induced emission (AIE) mechanisms.