Search

Abstract\nPLAIN LANGUAGE SUMMARYSystemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score). Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) was conducted using the 10x Genomics technique. We observed upregulation of genes like CCDC15 and TRBV4-2 in T cells and CMPK2, IFIT1, and OAS2 in monocytes in the SLE-C group. Notably, gene sets related to Cell Cycle and IFN Response showed significant differences between the SLE-C and SLE-NC groups in naïve CD8 T cells. Our comparison of immune cell type ratios and transcriptional patterns between active and inactive SLE during pregnancy sheds light on the single-cell level changes in SLE status during pregnancy, offering insights for future SLE prediction and treatment strategies.Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Furthermore, SLE women have an increased likelihood of encountering adverse pregnancy outcomes such as diabetes and hypertension. The etiology of SLE involves a multifaceted interplay of genetic, immune, endocrine, and environmental factors, which contributes to a breakdown in the immune system’s tolerance to self-antigens. Recent studies have highlighted a strong correlation between the severity of renal involvement in lupus nephritis and B cell dysfunction in patients, as elucidated through single-cell transcriptomics. Additionally, comparative studies have revealed notable differences in the immune cell profile between pregnant women with lupus and healthy pregnant women. A key observation the marked reduction in the proportion of CD4+ T cells in pregnant women suffering from lupus. Despite these findings, the detailed transcriptomic alterations within high-resolution immune cell profiling during activate phase of SLE in pregnancy remain inadequately understood. In our study, we focused on comparing the transcriptomic expression patterns of peripheral blood immune cells between pregnant women with active SLE and those with stable SLE. Our data confirmed significant differences in IFN signaling and pregnancy-related factors in T cells, NK cells, B cells, and macrophages, contrasting the immune cells of pregnant women with active SLE against those with stable SLE. Additionally, the proportion of CD56+ NK cells was significantly increased in pregnant women with SLE. The correlation between the transcriptomic profiles of immune cells and the activity of SLE during pregnancy may provide potential strategies for predicting and treating SLE during pregnancy. [ABSTRACT FROM AUTHOR]

With the growing requirement for lightweight structural materials in automotive, aerospace, and infrastructure applications, multi‐material joints made with adhesive have attracted intense research interest. Commercial thermoset adhesives are one‐time cures, and difficult to disassemble the bonded components for repair and recycling. Our prior work with a thermoplastic acrylonitrile‐butadiene‐lignin rubber (ABL) addresses this sustainability/recycling challenge, but the adhesive exhibits deficient joining strength compared to standard thermosets. Here, we modify the ABL matrix by loading particulate fillers to enhance its modulus and toughness. The goal is to manufacture a cure‐free thermoplastic adhesive system with a simple dispensing protocol and characteristic ductility combined with a high yield stress for improved shear strength of a bonded joint. Fumed silica (FS) and epoxidized glass spheres (EGS) were used as fillers in the ABL to promote the dispersion of lignin particles that tailored the functionalities and free energy components of the adhesive surface. With optimal loading of FS (5 wt%) and EGS (30 wt%) in the ABL adhesive matrix, the lap‐shear strength of the bonded aluminum joint was elevated by 128%, compared to the neat ABL, reaching 21 MPa, which is 90% of the performance of a commercial epoxy‐based adhesive. Highlights: A partly renewable filler‐toughened thermoplastic adhesive has been developed.This thermoplastic gives nearly equivalent performance of adhesively bonded aluminum joint compared to standard thermosets.Experimental and simulation data help understand the adhesive reinforcing mechanism by the fillers. [ABSTRACT FROM AUTHOR]

The rapid growth of urban populations has resulted in a scarcity of land, thus making sustainable urban development an urgent matter. Although Shenzhen has implemented land policies and optimized its functional layouts, these measures have inadvertently contributed to a shortage of available land for development. The city's exponential population growth and expansive urban expansion have outpaced the supply of land. This study endeavors to identify urban commercial patterns by employing multiple data sources and applying machine learning and network analysis to predict future commercial areas. The results demonstrated that the identification of commercial points of interest and analysis of land surface temperature distributions made Futian district the primary area for ongoing commercial development, while also revealing a positive correlation between these two datasets. By leveraging network analysis to thoroughly examine this data, Bao'an district was highlighted as the future focal point for Shenzhen's commercial sector, with 22 core nodes identified in total. Finally, by assessing the network centrality within the spatial networks, and utilizing clustering algorithms to categorize nodes into groups, the economic clustering pattern was determined as the predominant model for Shenzhen's commercial growth. This research represents a significant contribution to the realm of sustainable urban development and presents a valuable framework for other cities to adopt. [ABSTRACT FROM AUTHOR]

Since the 1970s, mankind has become increasingly sensitive to major world environmental protection issues, and the globalenvironmental protection laws and regulations system formed to deal with suchspecific issues has rapidly expanded in scope and depth. From the initial environmental issues in the study of international relations theory to the development of environmental issues in the study of global governance, and then the concept of global environmental governance came out and developed rapidly. This trend provides a desire to deal with many environmental protection issues and various issues related to worldenvironmental protection issues. But are these wishes real? We must also doubtthe rationality of the legal systems of various countries that have been formedand fought to deal with all environmental protection relations, especially theworld environmental protection issues. Today, the world environmental problemhas formed a relatively perfect academic field. The concept theory of globalproblems starting from ecological problems has moved from ecological problemsto world governance problems. With the introduction and rapid improvement ofthe concept of world ecological problems. The articlestarts from the role of non-state actors in the original internationalframework, further expands and deepens, and presents a multiangle andall-round perspective, showing that international law can still play a crucial role in the settlement of international environmental problems. It not only caters to the needs of the current international situation and development but also provides forward-looking guidance for future environmental governance at the global level. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article Acrylonitrile‐butadiene‐lignin thermoplastic rubber adhesive for enhanced metal‐to‐metal joining by Zeyang Yu et al., https://doi.org/10.1002/pc.28258. [ABSTRACT FROM AUTHOR]

Objectives: Despite being a key population in whom to initiate pre‐exposure prophylaxis (PrEP), the awareness of and willingness to use PrEP are still unclear in Chinese young men who have sex with men (YMSM). We report factors associated with PrEP awareness and willingness in the population. Methods: From 1 August to 31 December 2018, 495 participants aged 15–24 years were included in a cross‐sectional study about awareness of and willingness to use PrEP among YMSM. Logistic regression models were used to identify factors associated with two outcomes: awareness of PrEP; and willingness to use PrEP. Results: Among 495 eligible participants, 129 participants (26.1%) knew about PrEP. PrEP awareness among YMSM was associated with higher education level [adjusted odds ratio (aOR) = 1.812, 95% CI: 1.113–2.951] and previous HIV testing (aOR = 3.507, 95% CI: 1.261–9.752). YMSM with shorter local residence time (aOR = 0.317, 95% CI: 0.101–0.992) and internet‐based partner‐seeking (aOR = 0.171, 95% CI: 0.096–0.305) were less likely to be aware of PrEP. In those with previous knowledge of PrEP, 36 (27.9%) conveyed their willingness to use it. PrEP willingness was associated with internet‐based partner‐seeking (aOR = 9.593, 95% CI: 1.965–46.844). The main barriers influencing those who knew about PrEP but refused to use it were the high price of PrEP (69.9%), the need to use condoms consistently (52.7%), and concerns about side effects (39.8%) and effectiveness of prevention (22.6%). Conclusions: Chinese YMSM have low awareness of and willingness to use PrEP. Adequate PrEP promotions should be implemented, especially on the Internet and dating software. [ABSTRACT FROM AUTHOR]

The interface design plays a crucial role in developing superior mechanical performance of graphene nanoplatelets (GnP)/epoxy composite. Here, graphene oxide (GO) was applied as the coupling agent, because of π‐π interaction it formed with GnP and its rich surface functional groups. GO‐GnP couple was prepared and further it was treated separately with two diamines with different chain length (p‐phenylenediamine [PPDA] and Jeffamine D2000) producing functionalized GO‐GnP couple (f‐(GO‐GnP)). The chemical bonds formed between the amine functional groups on GO surface and epoxy resin during the curing process providing strong sheet/matrix interfacial adhesion. GO‐GnP/f‐(GO‐GnP) filler with two different weight ratios between GO and GnP (1:10 and 1:50) used as the fillers for preparing epoxy based composite with 0.43 and 0.86 wt% filler loading. For the tensile modulus, PPDA‐f‐(GO‐GnP: 1:10) sample gave ~40% improvement under 0.43 wt%, while at 0.86 wt%, the reinforcing result raised up to ~60% for PPDA‐f‐(GO‐GnP:1:50) sample. GO‐GnP couple/functionalized GO‐GnP couple gave up to ~110% improvement in toughness compared to simply using GnP at 0.86 wt% filler loading. [ABSTRACT FROM AUTHOR]

Background Widespread opsin expression in the cortex of rats, where transgenic models have not been established, is not practical to achieve with the traditional diffusion-based virus transduction methods (DBD). New method We developed protocols for convection-enhanced delivery (CED) of virus for optogenetic transduction of the rat cortex. Targeting the motor forelimb area as an example, we performed dual-site CED (6 μL of virus per site, 3 mm pitch between sites) in the rat motor cortex. Results We identified injection parameters optimized for horizontal spread of infusate in the agarose gel model and then demonstrated in vivo widespread opsin expression over the cortical area (7.4 ± 1.0 mm in the AP direction, 4.4 ± 1.1 mm in the ML direction, N = 13 rats) using CED. The optogenetic transduction was also functionally robust, in which both optical modulation of neuronal activity and elicitation of overt motor responses was reliably observed. Comparison with existing method(s) CED led to about 24-fold increase in the volume of opsin expression, compared with the conventional DBD method. The total injection time was also reduced by at least 10 times, if similar extent of expression were to be achieved with the conventional DBD method. Conclusions CED is a reliable and effective method of virus delivery for optogenetic transduction of planar superficial structures, such as the cortex in rats. [ABSTRACT FROM AUTHOR]

The twin-wire arc additive manufacturing (TWAAM) technology is an effective method for the in-situ fabrication of Ti 2 AlNb-based alloys relative to conventional cast and wrought routes. However, composition segregation is still challenging in the field of in-situ TWAAM. To homogenize the chemical composition, here we proposed a novel single droplet pre-alloying transfer mode of TWAAM based on the original droplet transfer mode of double wires directly fed into the molten pool. The designed nominal composition of Ti-25Al-23Nb was set as the target alloy. The as-printed parts were investigated systematically. The results showed that this unique droplet transfer mode could not only improve the forming accuracy but also effectively mitigate the composition segregation. In addition, the inconsistency of microstructure caused by the composition segregation was successfully solved by this mode and appears a fully lamellar microstructure. The improvement of composition uniformity played a positive role in enhancing the mechanical properties of the alloy, in which the tensile strength of room and high temperature were improved by 76.8% and 74.1% respectively compared with our previous research. This work is of great significance to alleviate the composition segregation of intermetallics and further promote the in-situ TWAAM fabrication of Ti 2 AlNb-based alloys. • The composition segregation that challenges the Ti 2 AlNb-based alloy in-situ fabricated by twin-wire arc additive manufacturing (TWAAM) was successfully mitigated by a novel single droplet pre-alloying transfer mode. • This single droplet pre-alloying transfer mode also promotes the forming stability and accuracy during the TWAAM process. • The improvement of composition uniformity played a positive role in solving the inconsistency of microstructure and enhancing the mechanical properties. [ABSTRACT FROM AUTHOR]

To better apply the biocontrol agent Trichoderma spp. in Northeast China, collecting and screening more suitable native Trichoderma strains is necessary. In the present study, 10 isolates were obtained from Juglans mandshurica rhizosphere soils in Heilongjiang Province, and were identified as T. asperellum (four isolates), T. harzianum (four), T. hamatum (one), T. atroviride (one). The fastest-growing isolate per species on potato dextrose agar medium were further evaluated in stress tolerance tests (salt, alkali, nutritional stress, and low temperature) and confrontation assays (eight pathogens), which showed that T. asperellum TaspHu1 possessed the best adaptation and biological control ability. Then, Solanum lycopersicum (tomato) seeds were sown and treated with a series of concentrations of TaspHu1 spore suspension, as was unsown soil. Tomato seedlings treated by TaspHu1 had a significantly greater height, stem diameter, soluble protein content and soluble sugar content. Furthermore, their nitrate reductase activity and catalase activity were significantly increased, and these promoting effects depended on the concentration of the spore suspension. Meanwhile, a decrease in chlorophyll content was observed in the tomato seedlings treated with TaspHu1. In addition, strain TaspHu1 enhanced the tomato seedlings' absorption of available nitrogen, but did not influence the soil available nitrogen content. Furthermore, the resistance of tomato seedlings against Alternaria alternata was enhanced by TaspHu1 (smaller, fewer leaf spots), the seedlings' hormone signal transduction genes JAR1 , MYC2 , NPR1, PR1 , and GH3.2 were highly expressed. Thus, TaspHu1 is a promising biocontrol candidate for use in agriculture and forestry. [ABSTRACT FROM AUTHOR]

The TabZIP15 gene encoding a 396 amino acid (aa) polypeptide in the fungus Trichoderma asperellum ACCC30536 was cloned and characterised. The protein includes a basic region motif (NR-x2-QR-x2-R) and has a pillar-like structure. The 25 basic region/leucine zipper transcription factors (TFs) identified in the T. asperellum genome were divided into YAP (14 TFs), ATF2 (5), GCN4 (2), Zip1 (2), BRLZ (1) and u1 (1) subfamilies based on conserved domains. T. asperellum was cultured in minimal media (MM) control, C-Hungry and N-Hungry medium (to simulate nutrient competition and interaction with pathogens, respectively), and differential expression analysis showed that 14 TabZIP genes (including TabZIP15) were significantly altered under both conditions; TabZIP23 responded strongly to N-Hungry media and TabZIP24 responded strongly to C-Hungry media. However, only YAP genes TabZIP15, TabZIP12 and TabZIP2 were significantly upregulated under both conditions, and expression levels of TabZIP15 were highest. T. asperellum was also cultured in the presence of five fungal pathogenic toxins, and RT-qPCR results showed that TabZIP15 was significantly upregulated in four of the five toxin stress conditions (MM + Rhizoctonia solani, MM + Fusarium oxysporum, MM + Alternaria alternata and MM + Cytospora chrysosperma). [ABSTRACT FROM AUTHOR]

Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus ( β = 0.018, P = 2.383 × 10 -4 ) and negatively associated with the volumes of the bilateral caudate (left: β = -0.020, P = 7.203 × 10 -5 ; right: β = -0.021, P = 3.274 × 10 -5 ) and putamen nuclei (left: β = -0.030, P = 2.175 × 10 -8 ; right: β = -0.024, P = 1.047 × 10 -5 ). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus ( β = 0.023, P = 1.025 × 10 -4 ). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder., Competing Interests: The authors report no competing interests related to the study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Objective: Pancreatic ductal adenocarcinoma (PDAC) is 3 rd most lethal cancer in the USA leading to a median survival of six months and less than 5% 5-year overall survival (OS). As the only potentially curative treatment, surgical resection is not suitable for up to 90% of the patients with PDAC due to late diagnosis. Highly fibrotic PDAC with an immunosuppressive tumor microenvironment restricts cytotoxic T lymphocyte (CTL) infiltration and functions causing limited success with systemic therapies like dendritic cell (DC)-based immunotherapy. In this study, we investigated the potential benefits of irreversible electroporation (IRE) ablation therapy in combination with DC vaccine therapy against PDAC., Methods: We performed a literature search to identify studies focused on DC vaccine therapy and IRE ablation to boost therapeutic response against PDAC indexed in PubMed, Web of Science, and Scopus until February 20 th , 2023., Key Content and Findings: IRE ablation destructs tumor structure while preserving extracellular matrix and blood vessels facilitating local inflammation. The studies demonstrated IRE ablation reduces tumor fibrosis and promotes CTL tumor infiltration to PDAC tumors in addition to boosting immune response in rodent models. The administration of the DC vaccine following IRE ablation synergistically enhances therapeutic response and extends OS rates compared to the use of DC vaccination or IRE alone. Moreover, the implementation of data-driven approaches further allows dynamic and longitudinal monitoring of therapeutic response and OS following IRE plus DC vaccine immunoablation., Conclusions: The combination of IRE ablation and DC vaccine immunotherapy is a potent strategy to enhance the therapeutic outcomes in patients with PDAC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-1882/coif). Zigeng Zhang reports a grant from Society of Interventional Radiology Foundation. A.E. reports a pilot grant from the University of California Irvine Anti-Cancer Challenge. V.Y. and Zhuoli Zhang report grants from the National Institute of Health. The other authors have no conflicts of interest to declare., (2024 Annals of Translational Medicine. All rights reserved.)

The integral probability metric (IPM) equips generative adversarial nets (GANs) with the necessary theoretical support for comparing statistical moments in an embedded domain of the critic, while stabilising their training and mitigating the mode collapse issues. For enhanced intuition and physical insight, we introduce a generalisation of IPM-GANs which operates by directly comparing probability distributions rather than their moments. This is achieved through characteristic functions (CFs), a powerful tool that uniquely comprises all information about any general distribution. For rigour, we first theoretically prove the ability of the CF loss to compare probability distributions, and proceed to establish the physical meaning of the phase and amplitude of CFs. An optimal sampling strategy is then developed to calculate the CFs, and an equivalence between the embedded and data domains is proved under the reciprocal theory. This makes it possible to seamlessly combine IPM-GAN with an auto-encoder structure by an advanced anchor architecture, which adversarially learns a semantic low-dimensional manifold for both generation and reconstruction. This efficient reciprocal CF GAN (RCF-GAN) structure, uses only two modules and a simple training strategy to achieve the state-of-the-art bi-directional generation. Experiments demonstrate the superior performance of RCF-GAN on both regular (images) and irregular (graph) domains.

Background: The HIV epidemic in key populations such as men who have sex with men (MSM) is a public health issue of worldwide concern. China has seen an increase in newly diagnosed HIV infections through male-male sexual contact in the past decade. In a long-term cohort, how the complex behaviour pattern of MSM changed and the association with the HIV risk are unclear at present., Methods: This study was conducted from October 2011 to December 2019 in Tianjin. MSM were recruited by snowball sampling through online and offline ways. Demographic and sexual behavioural data were collected for analysis. Three indicators (condom use in last anal sex, frequency of condom use during anal sex and the number of sexual partners) were used to define the behaviour change. Participants with zero, one, and two or three risk indicators were categorised into behaviour types of 'protective', 'moderate', and 'fragile', respectively. Change in behaviour type between baseline and each visit was considered. Time-varying Cox models were performed to evaluate HIV infection risk., Results: Of 2029 MSM included in the study, 127 were new HIV diagnoses. The overall incidence rate was 3.36 per 100 person-years. The percentage of 'protective' and 'moderate' behaviour types had a conspicuous growth trend as the follow-up. Furthermore, the HIV incidence rate in each visit among different behaviour transition types showed a general downward trend as the number of total follow-up times increased. Individuals who remained in 'fragile' (adjusted HR (aHR): 25.86, 95% CI: 6.92 to 96.57) or changed from 'protective' to 'moderate' (aHR: 4.79, 95% CI: 1.18 to 19.47), 'protective' to 'fragile' (aHR: 23.03, 95% CI: 6.02 to 88.13), and 'moderate' to 'fragile' (aHR: 25.48, 95% CI: 6.79 to 95.40) between baseline and the last follow-up had a higher HIV risk. Gained risk indicators were associated with the increase of HIV risk (gained one indicator, aHR: 2.67, 95% CI: 1.68 to 4.24; gained two or three indicators, aHR: 4.99, 95% CI: 3.00 to 8.31) while losing just one risk indicator could halve the risk (aHR: 0.43, 95% CI: 0.21 to 0.90)., Conclusions: Among MSM in Tianjin, it is necessary to get timely behaviour change for those with high-incidence behaviour patterns while sustaining for those with low-incidence patterns., Trial Registration Number: Chinese Clinical Trials Registry (ChiCTR2000039500)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pathological angiogenesis is the hallmark of many vision-threatening diseases. Anti-VEGF is a primary treatment with substantial beneficial effects. However, such agents require frequent intravitreal injections. Our previous work established a method for effectively modifying exosomes (EXOs) for loading therapeutic peptides. Here, we used this system to load the anti-angiogenic peptide KV11, aiming to establish an EXO-based therapy strategy to suppress neovascularization in the retina. Methods: Using an anchoring peptide, CP05, we linked KV11 to endothelial cell (EC) derived EXOs, yielding EXO KV11 . We tested the delivery efficiency of EXO KV11 via two commonly used ocular injection methods: retro-orbital injection and intravitreal injection. Deploying an oxygen-induced retinopathy (OIR) model and a VEGF injection model, we tested the effects of EXO KV11 on neovascular formation, EC proliferation, and vascular permeability. In vitro experiments were used to test the mechanism and to analyze the effects of EXO KV11 on EC proliferation, migration, and sprouting. Results : By using the EXO loading system, KV11 was more efficiently delivered to the blood vessels of the mouse retina via retro-orbital injection. In both OIR model and VEGF injection model, EXO KV11 was more effective than KV11 alone in inhibiting neovascularization and vessel leakage. The therapeutic effect of retro-orbital injection of EXO KV11 was comparable to the intravitreal injection of VEGF-trap. Mechanistically, KV11 alone inhibited VEGF-downstream signaling, while EXO KV11 showed a stronger effect. Conclusions: We used EXOs as a carrier for intraocular delivery of KV11. We showed that KV11 itself has an anti-angiogenic effect through retro-orbital injection, but that this effect was greatly enhanced when delivered with EXOs. Thus, this system has the potential to treat proliferative retinopathy via retro-orbital injection which is a less invasive manner compared with intravitreal injection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Graphene nanoplatelets (GnP) can be made into a thin 'paper' through vacuum filtration of GnP suspension. Electrodes were fabricated from the compressed GnP paper and then by coating the surface with epoxy. The electrostatic actuator was constructed from two parallel-aligned composite papers fixed at the anode and a cathode connected to ground. The two composite papers would then separate when a voltage was applied. The GnP paper was also modified to increase surface area by introducing porosity or adding ∼10 wt% C750 (GnP with diameter less than 1 μm); or changing the relative permittivity by adding barium titanate particles; or combining these two effects by adding CNCs. Overall the output work could be significantly improved to over 400%.

Dopamine (DA) release and uptake dynamics in the nucleus accumbens (NAc) have important implications for neurological diseases and mammalian animal behaviors. We demonstrate here the use of cell-type-specific optogenetic targeting in conjunction with fast-scan cyclic voltammetry applied to brain slices prepared from specifically tailored transgenic mice, which conditionally express channelrhodopsin-2 (ChR2) through dopamine transporter (DAT)-Cre. Terminal dopaminergic dynamics and the direct manipulation of induced DA release level by controlling light intensity, pulse width, and the shape of stimulation waveforms were studied. Effective cell terminal-targeting optogenetic induction of DA release at physiological levels in NAc is demonstrated and discussed. It was found that delivering more light energy by increasing stimulation intensity and length is not the only way to control DA release; the temporal shape of the stimulus waveform at light onset is also critically related to induced DA concentrations. In addition, DA uptake dynamics as well as the recovery of the presynaptic releasable DA pool are studied and modeled. More broadly, our experimental findings provide important further evidence for effectively applying optogenetics to induce neurotransmitter release in the behaviorally relevant region of the brain in a highly cell-type selective context.