Cannabidiol ameliorates PTSD-like symptoms by inhibiting neuroinflammation through its action on CB2 receptors in the brain of male mice.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disease related to traumatic experience, and its treatment outcomes are unsatisfactory. Accumulating research has indicated that cannabidiol (CBD) exhibits anti-PTSD effects, however, the underlying mechanism of CBD remains inadequately investigated. Although many studies pertaining to PTSD have primarily focused on aberrations in neuronal functioning, the present study aimed to elucidate the involvement and functionality of microglia/macrophages in PTSD while also investigated the modulatory effects of CBD on neuroinflammation associated with this condition. We constructed a modified single-prolonged stress (SPS) mice PTSD model and verified the PTSD-related behaviors by various behavioral tests (contextual freezing test, elevated plus maze test, tail suspension test and novel object recognition test). We observed a significant upregulation of Iba-1 and alteration of microglial/macrophage morphology within the prefrontal cortex and hippocampus, but not the amygdala, two weeks after the PTSD-related stress, suggesting a persistent neuroinflammatory phenotype in the PTSD-modeled group. CBD (10 mg/kg, i.p.) inhibited all PTSD-related behaviors and reversed the alterations in both microglial/macrophage quantity and morphology when administered prior to behavioral assessments. We further found increased pro-inflammatory factors, decreased PSD95 expression, and impaired synaptic density in the hippocampus of the modeled group, all of which were also restored by CBD treatment. CBD dramatically increased the level of anandamide, one of the endocannabinoids, and cannabinoid type 2 receptors (CB2Rs) transcripts in the hippocampus compared with PTSD-modeled group. Importantly, we discovered the expression of CB2Rs mRNA in Arg-1-positive cells in vivo and found that the behavioral effects of CBD were diminished by CB2Rs antagonist AM630 (1 mg/kg, i.p.) and both the behavioral and molecular effects of CBD were abolished in CB2Rs knockout mice. These findings suggest that CBD would alleviate PTSD-like behaviors in mice by suppressing PTSD-related neuroinflammation and upregulation and activation of CB2Rs may serve as one of the underlying mechanisms for this therapeutic effect. The present study offers innovative experimental evidence supporting the utilization of CBD in PTSD treatment from the perspective of its regulation of neuroinflammation, and paves the way for leveraging the endocannabinoid system to regulate neuroinflammation as a potential therapeutic approach for psychiatric disorders.

Brain endothelial GSDMD activation mediates inflammatory BBB breakdown.

The blood-brain barrier (BBB) protects the central nervous system from infections or harmful substances1; its impairment can lead to or exacerbate various diseases of the central nervous system2-4. However, the mechanisms of BBB disruption during infection and inflammatory conditions5,6 remain poorly defined. Here we find that activation of the pore-forming protein GSDMD by the cytosolic lipopolysaccharide (LPS) sensor caspase-11 (refs. 7-9), but not by TLR4-induced cytokines, mediates BBB breakdown in response to circulating LPS or during LPS-induced sepsis. Mice deficient in the LBP-CD14 LPS transfer and internalization pathway10-12 resist BBB disruption. Single-cell RNA-sequencing analysis reveals that brain endothelial cells (bECs), which express high levels of GSDMD, have a prominent response to circulating LPS. LPS acting on bECs primes Casp11 and Cd14 expression and induces GSDMD-mediated plasma membrane permeabilization and pyroptosis in vitro and in mice. Electron microscopy shows that this features ultrastructural changes in the disrupted BBB, including pyroptotic endothelia, abnormal appearance of tight junctions and vasculature detachment from the basement membrane. Comprehensive mouse genetic analyses, combined with a bEC-targeting adeno-associated virus system, establish that GSDMD activation in bECs underlies BBB disruption by LPS. Delivery of active GSDMD into bECs bypasses LPS stimulation and opens the BBB. In CASP4-humanized mice, Gram-negative Klebsiella pneumoniae infection disrupts the BBB; this is blocked by expression of a GSDMD-neutralizing nanobody in bECs. Our findings outline a mechanism for inflammatory BBB breakdown, and suggest potential therapies for diseases of the central nervous system associated with BBB impairment.

Rhodamine-based fluorescent probe for dynamic STED imaging of mitochondria.

Stimulated emission depletion (STED) microscopy holds tremendous potential and practical implications in the field of biomedicine. However, the weak anti-bleaching performance remains a major challenge limiting the application of STED fluorescent probes. Meanwhile, the main excitation wavelengths of most reported STED fluorescent probes were below 500 nm or above 600 nm, and few of them were between 500-600 nm. Herein, we developed a new tetraphenyl ethylene-functionalized rhodamine dye (TPERh) for mitochondrial dynamic cristae imaging that was rhodamine-based with an excitation wavelength of 560 nm. The TPERh probe exhibits excellent anti-bleaching properties and low saturating stimulated radiation power in mitochondrial STED super-resolution imaging. Given these outstanding properties, the TPERh probe was used to measure mitochondrial deformation, which has positive implications for the study of mitochondria-related diseases.

[Carbon Emission Characteristics and Influencing Factors of Typical Processes in Drinking Water Treatment Plant].

Based on the actual operating conditions and data monitoring, the carbon emission characteristics of typical processes of a drinking water treatment plant (DWTP) in Tianjin were studied. The total carbon emission intensity measured by CO2-eq was 0.254 kg·m-3, and the proportion of carbon emissions from electricity consumption and reagent consumption was 81.76% and 9.15%, respectively. The key carbon emission sectors of electricity consumption were the water supply pump house, ultrafiltration membrane process, and inlet pump house, which accounted for 50.99%-73.51%, 17.64%-20.70%, and 17.97%-22.40% of the total carbon emission from electricity consumption in the DWTP, respectively. The contribution of sodium hypochlorite to the carbon emission of reagent consumption was 89.12%-90.30%, followed by ferric chloride, PAC, and ammonium sulfate. In the traditional water purification process, the carbon emission intensity of the process unit was in the order of inlet pump house > rapid filter > sedimentation tank. The order in the ultrafiltration membrane advanced treatment process was inlet pump house > ultrafiltration membrane > mechanical coagulation > clarification tank. The carbon emission intensity of the rapid filter process and the ultrafiltration membrane process were 0.070 9 kg·m-3 and 0.109 0 kg·m-3, respectively. The ultrafiltration membrane process could save 23% of the reagent consumption, and its carbon emission of electricity consumption was twice that of the traditional treatment process. The analysis of factors affecting carbon emission in key sectors showed that the raw water quality parameters such as turbidity, pH, ammonia nitrogen, temperature, etc., were significantly correlated with the carbon emission intensity of sodium hypochlorite. There was a significant linear regression relationship between ex-factory water pressure, daily water supply, and carbon emission intensity of the water supply pump house. The control measures of water quality and water pressure can effectively reduce the carbon emissions of the DWTP.

Will changes in charging and gasoline prices affect electric vehicle sales? Evidence from China.

Electric vehicles and gasoline vehicles are substitutes for each other, and the cost of fuel is an important factor when consumers are faced with choices. Understanding the influence of changes in gasoline prices and charging prices on electric vehicle sales is of reference significance for promoting electric vehicles in the private sector. This paper uses data covering 212 prefecture-level cities from January, 2020, to August, 2022, for analysis, and the results show that different income groups have different sensitivities to the difference in oil and electricity prices. Additionally, changes in gasoline prices and charging prices will significantly affect electric vehicle sales in low-income and middle-income cities, electric vehicle sales in high-income cities will not be affected. Compared with nonpilot cities, residents of pilot cities are more sensitive to fuel price changes, indicating that the policy basis has a certain positive effect on the promotion of electric vehicles. It is recommended to consider the income status of regional residents when formulating policies for the use of electric vehicles. At the same time, publicity efforts should be increased to highlight the gap between the cost of fuel vehicles and electric vehicles.

Greenhouse gas emission inventory of drinking water treatment plants and case studies in China.

The Chinese government claimed to reach carbon dioxide emissions peaking by 2030 and achieve carbon neutralization by 2060. In this context, it's meaningful and urgent to estimate GHG emissions amount in every sectors. The growing concern about reducing GHG emissions has been shared by many water companies. This work aims to identify and estimate GHG emissions from the activities of drinking water treatment plants (DWTPs). According to the GHG protocol, the GHG emission inventory of DWTPs covers the sources of fossil fuel combustion, reservoir emissions, electricity and heat supply, use of chemicals and additives, disposal of waste, transportation, operation and maintenance. The tool was tested by nine DWTPs, which had an average GHG emission intensity of 0.225 kg CO2-eq/m3. The GHG emission intensities range from 0.167 kg CO2-eq/m3 to 0.272 kg CO2-eq/m3. The main source of GHG emissions is electricity supply, followed by the use of chemicals and additives. According to the average emission intensity, the estimated total amount of GHG emissions from DWTPs in China is about 1.82 × 107 t/a, corresponding to 0.15 % of the total GHG emission in China. The proposed GHG sources and emissions help decision-makers and DWTPs companies estimate GHG emissions more accurately and undertake GHG reduction measures.

Integrated neural tracing and in-situ barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors.

The circadian clock coordinates rhythms in numerous physiological processes to maintain organismal homeostasis. Since the suprachiasmatic nucleus (SCN) is widely accepted as the circadian pacemaker, it is critical to understand the neural mechanisms by which rhythmic information is transferred from the SCN to peripheral clocks. Here, we present the first comprehensive map of SCN efferent connections and suggest a molecular logic underlying these projections. The SCN projects broadly to most major regions of the brain, rather than solely to the hypothalamus and thalamus. The efferent projections from different subtypes of SCN neurons vary in distance and intensity, and blocking synaptic transmission of these circuits affects circadian rhythms in locomotion and feeding to different extents. We also developed a barcoding system to integrate retrograde tracing with in-situ sequencing, allowing us to link circuit anatomy and spatial patterns of gene expression. Analyses using this system revealed that brain regions functioning downstream of the SCN receive input from multiple neuropeptidergic cell types within the SCN, and that individual SCN neurons generally project to a single downstream brain region. This map of SCN efferent connections provides a critical foundation for future investigations into the neural circuits underlying SCN-mediated rhythms in physiology. Further, our new barcoded tracing method provides a tool for revealing the molecular logic of neuronal circuits within heterogeneous brain regions.

Dynamic Volumetric Imaging of Mouse Cerebral Blood Vessels In Vivo with an Ultralong Anti-Diffracting Beam.

Volumetric imaging of a mouse brain in vivo with one-photon and two-photon ultralong anti-diffracting (UAD) beam illumination was performed. The three-dimensional (3D) structure of blood vessels in the mouse brain were mapped to a two-dimensional (2D) image. The speed of volumetric imaging was significantly improved due to the long focal length of the UAD beam. Comparing one-photon and two-photon UAD beam volumetric imaging, we found that the imaging depth of two-photon volumetric imaging (80 µm) is better than that of one-photon volumetric imaging (60 µm), and the signal-to-background ratio (SBR) of two-photon volumetric imaging is two times that of one-photon volumetric imaging. Therefore, we used two-photon UAD volumetric imaging to perform dynamic volumetric imaging of mouse brain blood vessels in vivo, and obtained the blood flow velocity.

Multi-Exposure Image Fusion via Deformable Self-Attention.

Most multi-exposure image fusion (MEF) methods perform unidirectional alignment within limited and local regions, which ignore the effects of augmented locations and preserve deficient global features. In this work, we propose a multi-scale bidirectional alignment network via deformable self-attention to perform adaptive image fusion. The proposed network exploits differently exposed images and aligns them to the normal exposure in varying degrees. Specifically, we design a novel deformable self-attention module that considers variant long-distance attention and interaction and implements the bidirectional alignment for image fusion. To realize adaptive feature alignment, we employ a learnable weighted summation of different inputs and predict the offsets in the deformable self-attention module, which facilitates that the model generalizes well in various scenes. In addition, the multi-scale feature extraction strategy makes the features across different scales complementary and provides fine details and contextual features. Extensive experiments demonstrate that our proposed algorithm performs favorably against state-of-the-art MEF methods.

Environmental regulation and its influence on energy efficiency and environmental performance: do technology innovation and financial efficiency matter?

Global warming has recently become a significant concern for world leaders. Financial efficiency, environmental regulations, and green technologies are widely recognized as important contributors to a clean environment. Consequently, the primary motive of this study is to investigate the impact of financial efficiency, environmental regulations, and green technologies on CO2 emissions and energy efficiency in top polluted economies over the period 1995 to 2020. To that end, the study relies on the ARDL-PMG model, which can provide both short- and long-run estimates simultaneously. The findings of the model imply that environmental innovation and regulations helps improve energy efficiency and environmental quality in the long run. In contrast, financial development deteriorates the environmental quality and improves energy efficiency. Therefore, policy experts in top polluted economies must increase research and development activities to promote green technologies and introduce strict environmental-related regulations to complement other mitigating policies.

Green growth and environmental sustainability in China: the role of environmental taxes.

This study aims to investigate the impact of environmental-related taxes on green growth and CO2 emissions in China covering the time 1996-2019. To get the short- and long-run estimates, we have applied the bounds testing approach. Estimates of the study provide some important results. In the short run, environmental taxes and environmental policy stringency estimates are negatively significant in the CO2 emissions models and positively significant in the green growth models. Likewise, the long-run estimates attached to environmental taxes are significantly negative in the basic and robust CO2 emissions models while insignificant in the green growth models. However, the long-run estimates of environmental policy stringency are significantly negative in the basic and robust CO2 emissions models and significantly positive in the basic and robust green growth models. In general, our findings imply that an increase in environment-related taxes and strictness in environmental policies help reduce CO2 emissions and promote green growth in China.

Determinants of China's renewable energy industry development: do eco-innovation and financial inclusion matter?

Fossil fuels are causing irreparable damage to the environment and lead to the depletion of reservoirs of coal, oil, and gas, which may give rise to the issue of energy scarcity and security. Therefore, policymakers and empirics have looked for alternative sources of energy that are affordable, reliable, and clean sources of energy. Consistent with this view, we have tried to examine the impact of eco-innovation and financial inclusion on renewable energy development in China. In order to empirically investigate, we have applied the autoregressive distributive lag model. The long-run estimates of eco-innovations are statistically significant and positive models, confirming that environmental-related innovations help increase the production of different renewable energy. Similarly, the long-run estimates of financial inclusion are positively significant, implying that an increase in financial inclusiveness intensifies the production of solar, biomass, and renewable energy in China. Generally, our findings imply that both eco-innovations and financial inclusion help increase renewable energy production in China in the long run.

Revealing the effectiveness of green technological progress and financial innovation on green economic growth: the role of environmental regulation.

Green economic growth is the best alternative strategy for sustainable development. Existing literature investigated the determinants of green economic growth in China and provides mixed results. Thus, our study explores the impact of green environmental technology, financial innovation, and environmental regulations on green economic growth by controlling the impact of renewable energy consumption, trade, and education. The study explores the symmetric and asymmetric associations by employing ARDL and NARDL approaches. The ARDL long-run findings display that green environmental technologies, environmental regulations, and financial innovations positively and significantly contribute to green economic growth. However, the NARDL long-run findings infer that positive shock in green environmental technology, financial innovation, and environmental regulation exerts a significant and positive impact on green growth, while negative shock in green environmental technology, financial innovation, and environmental regulation has an insignificant impact on green growth. Based on the findings, the study delivers important policy implications to promote green economic growth in China.

A neuropsin-based optogenetic tool for precise control of Gq signaling.

Gq-coupled receptors regulate numerous physiological processes by activating enzymes and inducing intracellular Ca2+ signals. There is a strong need for an optogenetic tool that enables powerful experimental control over Gq signaling. Here, we present chicken opsin 5 (cOpn5) as the long sought-after, single-component optogenetic tool that mediates ultra-sensitive optical control of intracellular Gq signaling with high temporal and spatial resolution. Expressing cOpn5 in HEK 293T cells and primary mouse astrocytes enables blue light-triggered, Gq-dependent Ca2+ release from intracellular stores and protein kinase C activation. Strong Ca2+ transients were evoked by brief light pulses of merely 10 ms duration and at 3 orders lower light intensity of that for common optogenetic tools. Photostimulation of cOpn5-expressing cells at the subcellular and single-cell levels generated fast intracellular Ca2+ transition, thus demonstrating the high spatial precision of cOpn5 optogenetics. The cOpn5-mediated optogenetics could also be applied to activate neurons and control animal behavior in a circuit-dependent manner. cOpn5 optogenetics may find broad applications in studying the mechanisms and functional relevance of Gq signaling in both non-excitable cells and excitable cells in all major organ systems.

The double-edged role of the digital economy in firm green innovation: micro-evidence from Chinese manufacturing industry.

The digital economy, which gradually emerged with a new generation of information technologies, has become an unavoidable reality for manufacturing firms in conducting green innovation activities. In this context, using matched panel data at the province and manufacturing firm levels in China during the period 2011-2019 as the sample, this article examines the nonlinear impact of the digital economy on firm green innovation, and further identifies the moderation mechanism of government quality and the heterogeneity of its effects. The two-way fixed-effects model reveals that there is not a simple linear association between the digital economy and firm green innovation as traditionally perceived, but rather an inverted U-shaped relationship that first promotes and then inhibits, which remains robust after applying endogenous and robustness tests. And most provinces have not yet crossed the inflection point; thus, the digital economy overall positively impacts green innovation. Further analysis shows that government quality positively moderates the relationship between the digital economy and firm green innovation, statistically reflecting that the turning point shifts upwards to the right under a higher-quality government. It is worth noting that, when heterogeneity in firm ownership, scale, and region is considered, the inverted U-shaped curve still exists, but the level of the digital economy at the inflection point differs, and the digital economy plays a greater role in promoting green innovation for state-owned, large-scale, or midwestern firms. This research has significant policy implications as it establishes an inverse U-shaped relationship between the digital economy and firm green innovation and indicates that while a firm's green patent output increases with the development of digitalization, it begins to decrease after a limit.

Lactobacillus, Bifidobacterium and Lactococcus response to environmental stress: Mechanisms and application of cross-protection to improve resistance against freeze-drying.

The review deals with lactic acid bacteria in characterizing the stress adaptation with cross-protection effects, mainly associated with Lactobacillus, Bifidobacterium and Lactococcus. It focuses on adaptation and cross-protection in Lactobacillus, Bifidobacterium and Lactococcus, including heat shocking, cold stress, acid stress, osmotic stress, starvation effect, etc. Web of Science, Google Scholar, Science Direct, and PubMed databases were used for the systematic search of literature up to the year 2020. The literature suggests that a lower survival rate during freeze-drying is linked to environmental stress. Protective pretreatment under various mild stresses can be applied to lactic acid bacteria which may enhance resistance in a strain-dependent manner. We investigate the mechanism of damage and adaptation under various stresses including heat, cold, acidic, osmotic, starvation, oxidative and bile stress. Adaptive mechanisms include synthesis of stress-induced proteins, adjusting the composition of cell membrane fatty acids, accumulating compatible substances, etc. Next, we reveal the cross-protective effect of specific stress on the other environmental stresses. Freeze-drying is discussed from three perspectives including the regulation of membrane, accumulation of compatible solutes and the production of chaperones and stress-responsive proteases. The resistance of lactic acid bacteria against technological stress can be enhanced via cross-protection, which improves industrial efficiency concerning the survival of probiotics. However, the adaptive responses and cross-protection are strain-dependent and should be optimized case by case.

Nanodrug Transmembrane Transport Research Based on Fluorescence Correlation Spectroscopy.

Although conventional fluorescence intensity imaging can be used to qualitatively study the drug toxicity of nanodrug carrier systems at the single-cell level, it has limitations for studying nanodrug transport across membranes. Fluorescence correlation spectroscopy (FCS) can provide quantitative information on nanodrug concentration and diffusion in a small area of the cell membrane; thus, it is an ideal tool for studying drug transport across the membrane. In this paper, the FCS method was used to measure the diffusion coefficients and concentrations of carbon dots (CDs), doxorubicin (DOX) and CDs-DOX composites in living cells (COS7 and U2OS) for the first time. The drug concentration and diffusion coefficient in living cells determined by FCS measurements indicated that the CDs-DOX composite distinctively improved the transmembrane efficiency and rate of drug molecules, in accordance with the conclusions drawn from the fluorescence imaging results. Furthermore, the effects of pH values and ATP concentrations on drug transport across the membrane were also studied. Compared with free DOX under acidic conditions, the CDs-DOX complex has higher cellular uptake and better transmembrane efficacy in U2OS cells. Additionally, high concentrations of ATP will cause negative changes in cell membrane permeability, which will hinder the transmembrane transport of CDs and DOX and delay the rapid diffusion of CDs-DOX. The results of this study show that the FCS method can be utilized as a powerful tool for studying the expansion and transport of nanodrugs in living cells, and might provide a new drug exploitation strategy for cancer treatment in vivo.

Low-Power Two-Color Stimulated Emission Depletion Microscopy for Live Cell Imaging.

Stimulated emission depletion (STED) microscopy is a typical laser-scanning super-resolution imaging technology, the emergence of which has opened a new research window for studying the dynamic processes of live biological samples on a nanometer scale. According to the characteristics of STED, a high depletion power is required to obtain a high resolution. However, a high laser power can induce severe phototoxicity and photobleaching, which limits the applications for live cell imaging, especially in two-color STED super-resolution imaging. Therefore, we developed a low-power two-color STED super-resolution microscope with a single supercontinuum white-light laser. Using this system, we achieved low-power two-color super-resolution imaging based on digital enhancement technology. Lateral resolutions of 109 and 78 nm were obtained for mitochondria and microtubules in live cells, respectively, with 0.8 mW depletion power. These results highlight the great potential of the novel digitally enhanced two-color STED microscopy for long-term dynamic imaging of live cells.

Dual-color STED super-resolution microscope using a single laser source.

STED (stimulated emission depletion) microscopy is one of the most promising super-resolution fluorescence microscopies，due to its fast imaging and ultra-high resolution. In this paper, we present a dual-color STED microscope with a single laser source. Polarization beam splitters are used to separate the output from a supercontinuum laser source into four laser beams, including two excitation beams (488, 635 nm) and two depletion beams (592, 775 nm). These four laser beams are then used to build a low cost dual-color STED system to achieve a spatial resolution of 75 nm in cell samples.

Identification of a Novel Esterase from Marine Environmental Genomic DNA Libraries and Its Application in Production of Free All- trans-Astaxanthin.

Astaxanthin is a pigment with various functions. Free astaxanthin is obtained mainly through saponification methods, which could result in many byproducts. Enzymatic methods using lipases have been used in a few cases, while there are no reports on the use of esterases for the production of free astaxanthin. Herein we present the screening and identification of a novel esterase (Est3-14) from a marine mud metagenomic library. Est3-14 is pH-sensitive and keeps good stability in alkaline buffers (residual activity 94%, pH 8.0, 4 °C, and 36 h). Meanwhile, Est3-14 keeps a good stability in the medium temperature condition (residual activity 56.7%, pH 8.0, 40 °C, and 84 h). Est3-14 displayed high hydrolysis activity to prepare free all- trans-astaxanthin in biphasic systems. Furthermore, under optimal conditions (0.5 mL ethanol, 6 mL 0.1 M Tris-HCl buffer, pH 8.0, 0.5% (w/v) H. pluvialis oil, 40 °C), the hydrolytic conversion ratio was 99.3% after 36 h.