PLD3 affects axonal spheroids and network defects in Alzheimer's disease.

The precise mechanisms that lead to cognitive decline in Alzheimer's disease are unknown. Here we identify amyloid-plaque-associated axonal spheroids as prominent contributors to neural network dysfunction. Using intravital calcium and voltage imaging, we show that a mouse model of Alzheimer's disease demonstrates severe disruption in long-range axonal connectivity. This disruption is caused by action-potential conduction blockades due to enlarging spheroids acting as electric current sinks in a size-dependent manner. Spheroid growth was associated with an age-dependent accumulation of large endolysosomal vesicles and was mechanistically linked with Pld3-a potential Alzheimer's-disease-associated risk gene1 that encodes a lysosomal protein2,3 that is highly enriched in axonal spheroids. Neuronal overexpression of Pld3 led to endolysosomal vesicle accumulation and spheroid enlargement, which worsened axonal conduction blockades. By contrast, Pld3 deletion reduced endolysosomal vesicle and spheroid size, leading to improved electrical conduction and neural network function. Thus, targeted modulation of endolysosomal biogenesis in neurons could potentially reverse axonal spheroid-induced neural circuit abnormalities in Alzheimer's disease, independent of amyloid removal.

Enhancing Surface Strain of Intermetallic Fuel Cell Catalysts by Composition-Induced Phase Transition.

The lattice parameter of platinum-based intermetallic compounds (IMCs), which correlates with the intrinsic activity of the oxygen reduction reaction (ORR), can be modulated by crystal phase engineering. However, the controlled preparation of IMCs with unconventional crystal structures remains highly challenging. Here, we demonstrate the synthesis of carbon-supported PtCu-based IMC catalysts with an unconventional L10 structure by a composition-regulated strategy. Experiment and machine learning reveal that the thermodynamically favorable structure changes from L11 to L10 when slight Cu atoms are substituted with Co. Benefiting from crystal-phase-induced strain enhancement, the prepared L10-type PtCu0.8Co0.2 catalyst exhibits much-enhanced mass and specific activities of 1.82 A mgPt-1 and 3.27 mA cmPt-2, which are 1.91 and 1.73 times higher than those of the L11-type PtCu catalyst, respectively. Our work highlights the important role of crystal phase in determining the surface strain of IMCs, and opens a promising avenue for the rational preparation of IMCs with different crystal phases by doping.

2D Dual Gate Field-Effect Transistor Enabled Versatile Functions.

Advanced computing technologies such as distributed computing and the Internet of Things require highly integrated and multifunctional electronic devices. Beyond the Si technology, 2D-materials-based dual-gate transistors are expected to meet these demands due to the ultra-thin body and the dangling-bond-free surface. In this work, a molybdenum disulfide (MoS2 ) asymmetric-dual-gate field-effect transistor (ADGFET) with an In2 Se3 top gate and a global bottom gate is designed. The independently controlled double gates enable the device to achieve an on/off ratio of 106 with a low subthreshold swing of 94.3 mV dec-1 while presenting a logic function. The coupling effect between the double gates allows the top gate to work as a charge-trapping layer, realizing nonvolatile memory (105 on/off ratio with retention time over 104 s) and six-level memory states. Additionally, ADGFET displays a tunable photodetection with the responsivity reaching the highest value of 857 A W-1 , benefiting from the interface coupling between the double gates. Meanwhile, the photo-memory property of ADGFET is also verified by using the varying exposure dosages-dependent illumination. The multifunctional applications demonstrate that the ADGFET provides an alternative way to integrate logic, memory, and sensing into one device architecture.

A facile Immunoregulatory Constructional Design by Proanthocyanidin Optimizing Directional Chitosan Microchannel.

Improving the interconnected structure and bioregulatory function of natural chitosan is beneficial for optimizing its performance in bone regeneration. Here, a facile immunoregulatory constructional design is proposed for developing instructive chitosan by directional freezing and alkaline salting out. The molecular dynamics simulation confirmed the assembly kinetics and structural features of various polyphenols and chitosan molecules. Along with the in vitro anti-inflammatory, antioxidative, promoting bone mesenchymal stem cell (BMSC) adhesion and proliferation performance, proanthocyanidin optimizing chitosan (ChiO) scaffold presented an optimal immunoregulatory structure with the directional microchannel. Transcriptome analysis in vitro further revealed the cytoskeleton- and immune-regulation effect of ChiO are the key mechanism of action on BMSC. The rabbit cranial defect model (Φ = 10 mm) after 12 weeks of implantation confirmed the significantly enhanced bone reconstitution. This facile immunoregulatory directional microchannel design provides effective guidance for developing inducible chitosan scaffolds.

Manipulating 2D Materials through Strain Engineering.

This review explores the growing interest in 2D layered materials, such as graphene, h-BN, transition metal dichalcogenides (TMDs), and black phosphorus (BP), with a specific focus on recent advances in strain engineering. Both experimental and theoretical results are delved into, highlighting the potential of strain to modulate physical properties, thereby enhancing device performance. Various strain engineering methods are summarized, and the impact of strain on the electrical, optical, magnetic, thermal, and valleytronic properties of 2D materials is thoroughly examined. Finally, the review concludes by addressing potential applications and challenges in utilizing strain engineering for functional devices, offering valuable insights for further research and applications in optoelectronics, thermionics, and spintronics.

Silencing geranylgeranyltransferase I inhibits the migration and invasion of salivary adenoid cystic carcinoma through RhoA/ROCK1/MLC signaling and suppresses proliferation through cell cycle regulation.

Geranylgeranyltransferase type I (GGTase-I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase-I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase-I in mediating the malignant progression of SACC. The level of GGTase-I gene in cells was stably knocked down by short hairpin RNA-EGFP-lentivirus. The effects of GGTase-I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase-I and RhoA genes of SACC cells after GGTase-I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase-I on the above-mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p-MLC, E-cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1 . Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse-transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase-I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase-I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p-MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E-cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase-I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase-I is expected to serve as a novel exploration site of SACC.

2D van der Waals Vertical Heterojunction Transistors for Ternary Neural Networks.

Compared with binary systems, ternary computing systems can utilize fewer devices to realize the same information density. However, most ternary computing systems based on binary CMOS circuits require additional devices to bridge binary processing and ternary computing. Exploring new device architectures for direct ternary processing and computing becomes the key to promoting ternary computing systems. Here, we demonstrated a 2D van der Waals vertical heterojunction transistor (V-HTR) with three flat conductance states, which can be the basic cell in ternary circuits to perform ternary processing and computing, without additional devices. A ternary neural network (TNN) and a ternary inverter were demonstrated based on the V-HTRs. The TNN can eliminate fuzzy data and output only clear data by building a ternary quantization function. By demonstrating both ternary logic and a TNN on the same device architecture, the 2D V-HTR shows potential as a basic hardware unit for future ternary computing systems.

Characteristics and Source Apportionment of Volatile Organic Compounds in a Coastal Industrial Area: A Case Study in the Yangtze River Delta of China.

In recent years, the coastal area in East China has experienced elevated volatile organic compounds (VOCs) levels during specific periods. VOCs have become one of the major atmospheric pollutants in these areas. In this study, 64 compounds including alkanes, alkenes, halohydrocarbons, aromatics, and oxygenated VOCs (OVOCs) were obtained by the TO-15 method through a 12-month campaign in industrial, urban and suburban areas in the Yangtze River Delta of China. The overall trends of total VOC (TVOC) concentrations at eight sampling sites were as follows: winter > autumn > spring > summer. The proportion of VOC categories was various at industrial sites, while OVOCs and halohydrocarbons had high proportions at urban sites and suburban sites, respectively. Coating, vehicle emission, petrochemical source, industrial source, and gasoline volatilization were identified as the major VOC emission sources by the positive matrix factorization model. Petrochemical and coating sources were the prime VOC sources at industrial sites. Aromatics contributed the most ozone formation potential at industrial sites, while OVOCs provided the main contributions at both urban and suburban sites during four seasons. According to the health risk assessment, a high probability of non-carcinogenic risk existed at three industrial sites. Special attention should be given to certain VOCs, such as acrolein and 1,2-dibromoethane in industrial areas.

PDZD8-mediated endoplasmic reticulum-mitochondria associations regulate sympathetic drive and blood pressure through the intervention of neuronal mitochondrial homeostasis in stress-induced hypertension.

Neuronal hyperexcitation in the rostral ventrolateral medulla (RVLM) drives heightened sympathetic nerve activity and contributes to the etiology of stress-induced hypertension (SIH). Maintenance of mitochondrial functions is central to neuronal homeostasis. PDZD8, an endoplasmic reticulum (ER) transmembrane protein, tethers ER to mitochondria. However, the mechanisms of PDZD8-mediated ER-mitochondria associations regulating neuronal mitochondrial functions and thereby mediating blood pressure (BP) in the RVLM of SIH were largely unknown. SIH rats were subjected to intermittent electric foot shocks plus noise for 2 h twice daily for 15 consecutive days. The underlying mechanisms of PDZD8 were investigated through in vitro experiments by using small interfering RNA and through in vivo experiments, such as intra-RVLM microinjection and Western blot analysis. The function of PDZD8 on BP regulation in the RVLM was determined in vivo via the intra-RVLM microinjection of adeno-associated virus (AAV)2-r-Pdzd8. We found that the c-Fos-positive RVLM tyrosine hydroxylase (TH) neurons, renal sympathetic nerve activity (RSNA), plasma norepinephrine (NE) level, BP, and heart rate (HR) were elevated in SIH rats. ER-mitochondria associations in RVLM neurons were significantly reduced in SIH rats. PDZD8 was mainly expressed in RVLM neurons, and mRNA and protein levels were markedly decreased in SIH rats. In N2a cells, PDZD8 knockdown disrupted ER-mitochondria associations and mitochondrial structure, decreased mitochondrial membrane potential (MMP) and respiratory metabolism, enhanced ROS levels, and reduced catalase (CAT) activity. These effects suggested that PDZD8 dysregulation induced mitochondrial malfunction. By contrast, PDZD8 upregulation in the RVLM of SIH rats could rescue neuronal mitochondrial function, thereby suppressing c-Fos expression in TH neurons and decreasing RSNA, plasma NE, BP, and HR. Our results indicated that the dysregulation of PDZD8-mediated ER-mitochondria associations led to the loss of the activity homeostasis of RVLM neurons by disrupting mitochondrial functions, thereby participating in the regulation of SIH pathology.

Microglia-derived TNF-α contributes to RVLM neuronal mitochondrial dysfunction via blocking the AMPK-Sirt3 pathway in stress-induced hypertension.

BACKGROUND: Neuroinflammation in the rostral ventrolateral medulla (RVLM) has been associated with the pathogenesis of stress-induced hypertension (SIH). Neuronal mitochondrial dysfunction is involved in many pathological and physiological processes. However, the impact of neuroinflammation on neuronal mitochondrial homeostasis and the involved signaling pathway in the RVLM during SIH are largely unknown. METHODS: The morphology and phenotype of microglia and the neuronal mitochondrial injury in vivo were analyzed by immunofluorescence, Western blot, RT-qPCR, transmission electron microscopy, and kit detection. The underlying mechanisms of microglia-derived tumor necrosis factor-α (TNF-α) on neuronal mitochondrial function were investigated through in vitro and in vivo experiments such as immunofluorescence and Western blot. The effect of TNF-α on blood pressure (BP) regulation was determined in vivo via intra-RVLM microinjection of TNF-α receptor antagonist R7050. RESULTS: The results demonstrated that BP, heart rate (HR), renal sympathetic nerve activity (RSNA), plasma norepinephrine (NE), and electroencephalogram (EEG) power increased in SIH rats. Furthermore, the branching complexity of microglia in the RVLM of SIH rats decreased and polarized into M1 phenotype, accompanied by upregulation of TNF-α. Increased neuronal mitochondria injury was observed in the RVLM of SIH rats. Mechanistically, Sirtuin 3 (Sirt3) and p-AMPK expression were markedly downregulated in both SIH rats and TNF-α-treated N2a cells. AMPK activator A769662 upregulated AMPK-Sirt3 signaling pathway and consequently reversed TNF-α-induced mitochondrial dysfunction. Microinjection of TNF-α receptor antagonist R7050 into the RVLM of SIH rats significantly inhibited the biological activities of TNF-α, increased p-AMPK and Sirt3 levels, and alleviated neuronal mitochondrial injury, thereby reducing c-FOS expression, RSNA, plasma NE, and BP. CONCLUSIONS: This study revealed that microglia-derived TNF-α in the RVLM impairs neuronal mitochondrial function in SIH possibly through inhibiting the AMPK-Sirt3 pathway. Therefore, microglia-derived TNF-α in the RVLM may be a possible therapeutic target for the intervention of SIH.

Hydrophobic Tetracycline Immobilized in Fibrous Hyaluronan Regulates Adhesive Collagen-Based Hydrogel Stability for Infected Wound Healing.

Collagen-based hydrogels have a significant impact on wound healing, but they suffer from structural instability and bacterial invasion in infected wounds. Here, electrospun nanofibers of esterified hyaluronan (HA-Bn/T) are developed to immobilize the hydrophobic antibacterial drug tetracycline by π-π stacking interaction. Dopamine-modified hyaluronan and HA-Bn/T are employed simultaneously to stabilize the structure of collagen-based hydrogel by chemically interweaving the collagen fibril network and decreasing the rate of collagen degradation. This renders it injectable for in situ gelation, with suitable skin adhesion properties and long-lasting drug release capability. This hybridized interwoven hydrogel promotes the proliferation and migration of L929 cells and vascularization in vitro. It presents satisfactory antibacterial ability against Staphylococcus aureus and Escherichia coli. The structure also retains the functional protein environment provided by collagen fiber, inhibits the bacterial environment of infected wounds, and modulates local inflammation, resulting in neovascularization, collagen deposition, and partial follicular regeneration. This strategy offers a new solution for infected wound healing.

Covalently Grafted Biomimetic Matrix Reconstructs the Regenerative Microenvironment of the Porous Gradient Polycaprolactone Scaffold to Accelerate Bone Remodeling.

Integrating a biomimetic extracellular matrix to improve the microenvironment of 3D printing scaffolds is an emerging strategy for bone substitute design. Here, a "soft-hard" bone implant (BM-g-DPCL) consisting of a bioactive matrix chemically integrated on a polydopamine (PDA)-coated porous gradient scaffold by polyphenol groups is constructed. The PDA-coated "hard" scaffolds promoted Ca2+ chelation and mineral deposition; the "soft" bioactive matrix is beneficial to the migration, proliferation, and osteogenic differentiation of stem cells in vitro, accelerated endogenous stem cell recruitment, and initiated rapid angiogenesis in vivo. The results of the rabbit cranial defect model (Φ = 10 mm) confirmed that BM-g-DPCL promoted the integration between bone tissue and implant and induced the deposition of bone matrix. Proteomics confirmed that cytokine adhesion, biomineralization, rapid vascularization, and extracellular matrix formation are major factors that accelerate bone defect healing. This strategy of highly chemically bonded soft-hard components guided the construction of the bioactive regenerative scaffold.

Adjusting Surface Oxidized Layer of CoTe on PCN via In Situ N-Doping Strategy to Promote Charge Separation of Z-Scheme Heterojunction for Propelling Photocatalytic CO2 Reduction.

It has been a challenging issue to profoundly actuate the transfer and separation of photoinduced charge carriers by controlling the interface structure inside the heterojunction, owing to the molecular/subnanometric level interface region. Herein, a unique one-dimensional/two-dimensional (1D/2D) CoTe/PCN Z-scheme heterojunction is fabricated through the self-assembly of CoTe nanorods on the surface of polymeric carbon nitride (PCN) nanosheets. Significantly, in situ N-doping in the molecular/subnanometric surface oxidized layer of CoTe nanorods is achieved, effectively adjusting its chemical structure and element chemical states. Moreover, this N-doped surface oxidized layer can serve as a recombination region of photogenerated electrons from PCN and photogenerated holes from CoTe to increase the overall carrier separation efficiency in the Z-scheme heterojunction actuated by the built-in electric field. As a result, the photocatalytic CO2 reduction (CO2R) performance is enhanced dramatically, in which the yield of CO generated over the optimal 1D/2D CoTe/PCN heterojunction reaches up to triple than that over PCN. This unique contribution provides an emblematic paradigm for adjusting the interfacial structure of heterojunction and has a profound insight into the interfacial adjusting mechanism to improve the charge separation efficiency in the photocatalytic reaction.

Alloying Matters for Ordering: Synthesis of Highly Ordered PtCo Intermetallic Catalysts for Fuel Cells.

Porous carbon-supported atomically ordered intermetallic compounds (IMCs) are promising electrocatalysts in boosting oxygen reduction reaction (ORR) for fuel cell applications. However, the formation mechanism of IMC structures under high temperatures is poorly understood, which hampers the synthesis of highly ordered IMC catalysts with promoted ORR performance. Here, we employ high-temperature X-ray diffraction and energy-dispersive spectroscopic elemental mapping techniques to study the formation process of IMCs, by taking PtCo for example, in an industry-relevant impregnation synthesis. We find that high-temperature annealing is crucial in promoting the formation of alloy particles with a stoichiometric Co/Pt ratio, which in turn is the precondition for transforming the disordered alloys to ordered intermetallic structures at a relatively low temperature. Based on the findings, we accordingly synthesize highly ordered L10-type PtCo catalysts with a remarkable ORR performance in fuel cells.

Loss of Selenium from Mollisol Paddy Wetlands of Cold Regions: Insights from Flow-through Reactor Experiments and Process-Based Modeling.

Mollisols are critical agricultural resources for securing global food supply. Due to its health importance, selenium (Se) fate in the Mollisols attracts growing concerns. Land use change from conventional drylands to paddy wetlands impacts Se bioavailability in the vulnerable Mollisol agroecosystems. The underlying processes and mechanisms however remain elusive. Here, results of flow-through reactor experiments with paddy Mollisols from northern cold-region sites indicate that continuous flooding with surface water for 48 d induced redox zonation that facilitated the loss of Mollisol Se by up to 51%. Further process-based biogeochemical modeling suggests largest degradation rates of dissolved organic matter (DOM) in 30 cm deep Mollisols that contained the highest-level labile DOM and organic-bound Se. Electron shunting from degradation of Se-bearing DOM coupled to reductive dissolution of Se-adsorbed Fe oxides accounts mainly for Se(IV) release into the pore water. Consequent changes in DOM molecular composition make the reservoir of organic-bound Se vulnerable to flooding-induced redox zonation and likely enhance Se loss through destruction of thiolated Se and emission of gaseous Se from the Mollisol layer. This study highlights a neglected scenario where the speciation-driven loss of bioavailable Se from the paddy wetlands can be a significant consequence in the cold-region Mollisol agroecosystems.

Fluvial Deposition and Land Use Change Control Selenium Occurrence in Mollisols of Cold Region Agroecosystems.

Mollisols support the most productive agroecosystems in the world. Despite their critical links to food quality and human health, the varying distributions of selenium (Se) species and factors governing Se mobility in the mollisol vadose zone remain elusive. This research reveals that, in northern mollisol agroecosystems, Se hotspots (≥0.32 mg/kg) prevail along the regional river systems draining the Lesser Khingan Mountains, where piedmont Se-rich oil shales are the most probable source of regional Se. While selenate and selenite dominate Se species in the water-soluble and absorbed pools, mollisol organic matter is the major host for Se. Poorly crystalline and crystalline Fe oxides are subordinate in Se retention, hosting inorganic and organic Se at levels comparable to those in the adsorbed pool. The depth-dependent distributions of mollisol Se species for the non-cropland and cropland sites imply a predominance of reduced forms of Se under the mildly acidic and reducing conditions that, in turn, are variably impacted by agricultural land use. These findings therefore highlight that fluvial deposition and land use change together are the main drivers of the spatial variability and speciation of mollisol Se.

Distribution and risk assessment of antibiotics under water level fluctuation in the riparian zone of the Hanjiang River.

The riparian zone (RZ) is an important region connecting surface water and groundwater, and it has widely been acknowledged for its pollutant buffering capacity. However, the decontaminating effect of RZ on trace organic compounds such as antibiotics has received little attention. This study explored the distribution of 21 antibiotics and 4 sulfonamide metabolites in river water and groundwater in the lower reaches of the Hanjiang River. The diffusion and exchange of contaminants between the river and riverbanks under the influence of water conservancy projects (Xinglong Dam and the Yangtze-Hanjiang Water Diversion Project) were investigated. Macrolide antibiotics were prevalent in river water (62.5-100%) and groundwater samples (42.9-80.4%). Ofloxacin and chlortetracycline were detected with the highest concentrations in river water (12.2 ng L-1) and groundwater (9.3 ng L-1) respectively. Higher levels of antibiotics were observed in spring and winter than in other seasons. The river-groundwater interaction has a certain interception effect on antibiotics, especially near riverbanks. Redox sensitive element Fe2+ showed significantly positive correlations with some tetracycline and macrolide antibiotics (p < 0.05), and thus the migration mechanism between Fe2+ and antibiotics under the condition of redox change should be investigated further. Environmental risks posed by antibiotics were assessed for algae, daphnids, and fish in surface water and groundwater. Only clarithromycin and chlortetracycline presented a medium risk to algae (0.1 < RQ < 1), and the rest presented low risk (RQ < 0.1). Nevertheless, the risk range may be further extended by interactions between groundwater and surface water. Accurate understanding of antibiotic transport in RZ is critical for developing management strategies aimed at reducing the pollution load on the watershed.

Ultra-Reliable Deep-Reinforcement-Learning-Based Intelligent Downlink Scheduling for 5G New Radio-Vehicle to Infrastructure Scenarios.

Higher standards for reliability and efficiency apply to the connection between vehicle terminals and infrastructure by the fifth-generation mobile communication technology (5G). A vehicle-to-infrastructure system uses a communication system called NR-V2I (New Radio-Vehicle to Infrastructure), which uses Link Adaptation (LA) technology to communicate in constantly changing V2I to increase the efficacy and reliability of V2I information transmission. This paper proposes a Double Deep Q-learning (DDQL) LA scheduling algorithm for optimizing the modulation and coding scheme (MCS) of autonomous driving vehicles in V2I communication. The problem with the Doppler shift and complex fast time-varying channels reducing the reliability of information transmission in V2I scenarios is that they make it less likely that the information will be transmitted accurately. Schedules for autonomous vehicles using Space Division Multiplexing (SDM) and MCS are used in V2I communications. To address the issue of Deep Q-learning (DQL) overestimation in the Q-Network learning process, the approach integrates Deep Neural Network (DNN) and Double Q-Network (DDQN). The findings of this study demonstrate that the suggested algorithm can adapt to complex channel environments with varying vehicle speeds in V2I scenarios and by choosing the best scheduling scheme for V2I road information transmission using a combination of MCS. SDM not only increases the accuracy of the transmission of road safety information but also helps to foster cooperation and communication between vehicle terminals to realize cooperative driving.

Development of A Nanostructured Lipid Carrier-Based Drug Delivery Strategy for Apigenin: Experimental Design Based on CCD-RSM and Evaluation against NSCLC In Vitro.

Non-small-cell lung cancer (NSCLC) is the main cause of cancer-related deaths worldwide, with a low five-year survival rate, posing a serious threat to human health. In recent years, the delivery of antitumor drugs using a nanostructured lipid carrier (NLC) has become a subject of research. This study aimed to develop an apigenin (AP)-loaded nanostructured lipid carrier (AP-NLC) by melt sonication using glyceryl monostearate (GMS), glyceryl triacetate, and poloxamer 188. The optimal prescription of AP-NLC was screened by central composite design response surface methodology (CCD-RSM) based on a single-factor experiment using encapsulation efficiency (EE%) and drug loading (DL%) as response values and then evaluated for its antitumor effects on NCI-H1299 cells. A series of characterization analyses of AP-NLC prepared according to the optimal prescription were carried out using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). Subsequent screening of the lyophilization protectants revealed that mannitol could better maintain the lyophilization effect. The in vitro hemolysis assay of this formulation indicated that it may be safe for intravenous injection. Moreover, AP-NLC presented a greater ability to inhibit the proliferation, migration, and invasion of NCI-H1299 cells compared to AP. Our results suggest that AP-NLC is a safe and effective nano-delivery vehicle that may have beneficial potential in the treatment of NSCLC.

VOC characteristics and their source apportionment in a coastal industrial area in the Yangtze River Delta, China.

Volatile organic compounds (VOCs) are important precursors of secondary organic compounds and ozone, which raise major environmental concerns. To investigate the VOC emission characteristics, measurements of VOCs based on proton transfer reaction-mass spectrometry during 2017 were conducted in a coastal industrial area in Ningbo, Zhejiang Province, China. Based on seasonal variation in species concentration, the positive matrix factorization (PMF) receptor model was applied to apportion the sources of VOCs in each season. The PMF results revealed that unknown acetonitrile source, paint solvent, electronics industry, biomass burning, secondary formation and biogenic emission were mainly attributed to VOC pollution. Biomass burning and secondary formation were the major sources of VOCs and contributed more than 70% of VOC emissions in spring and autumn. Industry-related sources contributed 8.65%-31.2% of the VOCs throughout the year. The unknown acetonitrile source occurred in winter and spring, and contributed 7.6%-43.73% of the VOC emissions in the two seasons. Conditional probability function (CPF) analysis illustrated that the industry sources came from local emission, while biomass burning and biogenic emission mainly came from the northwest direction. The potential source contribution function (PSCF) model showed that secondary formation-related source was mainly from Jiangsu Province, northeastern China and the surrounding ocean. The potential source areas of unknown acetonitrile source were northern Zhejiang Province, southern Jiangsu Province and the northeastern coastal marine environments.