Effects of opioid-free anaesthesia compared with balanced general anaesthesia on nausea and vomiting after video-assisted thoracoscopic surgery: a single-centre randomised controlled trial.

OBJECTIVES: Opioid-free anaesthesia (OFA) has emerged as a promising approach for mitigating the adverse effects associated with opioids. The objective of this study was to evaluate the impact of OFA on postoperative nausea and vomiting (PONV) following video-assisted thoracic surgery. DESIGN: Single-centre randomised controlled trial. SETTING: Tertiary hospital in Shanghai, China. PARTICIPANTS: Patients undergoing video-assisted thoracic surgery were recruited from September 2021 to June 2022. INTERVENTION: Patients were randomly allocated to OFA or traditional general anaesthesia with a 1:1 allocation ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the incidence of PONV within 48 hours post-surgery, and the secondary outcomes included PONV severity, postoperative pain, haemodynamic changes during anaesthesia, and length of stay (LOS) in the recovery ward and hospital. RESULTS: A total of 86 and 88 patients were included in the OFA and control groups, respectively. Two patients were excluded because of severe adverse events including extreme bradycardia and epilepsy-like convulsion. The incidence and severity of PONV did not significantly differ between the two groups (29 patients (33.0%) in the control group and 22 patients (25.6%) in the OFA group; relative risk 0.78, 95% CI 0.49 to 1.23; p=0.285). Notably, the OFA approach used was associated with an increase in heart rate (89±17 vs 77±15 beats/min, t-test: p<0.001; U test: p<0.001) and diastolic blood pressure (87±17 vs 80±13 mm Hg, t-test: p=0.003; U test: p=0.004) after trachea intubation. Conversely, the control group exhibited more median hypotensive events per patient (mean 0.5±0.8 vs 1.0±2.0, t-test: p=0.02; median 0 (0-4) vs 0 (0-15), U test: p=0.02) during surgery. Postoperative pain scores, and LOS in the recovery ward and hospital did not significantly differ between the two groups. CONCLUSIONS: Our study findings suggest that the implementation of OFA does not effectively reduce the incidence of PONV following thoracic surgery when compared with traditional total intravenous anaesthesia. The opioid-free strategy used in our study may be associated with severe adverse cardiovascular events. TRIAL REGISTRATION NUMBER: ChiCTR2100050738.

Robust underwater image enhancement with cascaded multi-level sub-networks and triple attention mechanism.

With the growing exploration of marine resources, underwater image enhancement has gained significant attention. Recent advances in convolutional neural networks (CNN) have greatly impacted underwater image enhancement techniques. However, conventional CNN-based methods typically employ a single network structure, which may compromise robustness in challenging conditions. Additionally, commonly used UNet networks generally force fusion from low to high resolution for each layer, leading to inaccurate contextual information encoding. To address these issues, we propose a novel network called Cascaded Network with Multi-level Sub-networks (CNMS), which encompasses the following key components: (a) a cascade mechanism based on local modules and global networks for extracting feature representations with richer semantics and enhanced spatial precision, (b) information exchange between different resolution streams, and (c) a triple attention module for extracting attention-based features. CNMS selectively cascades multiple sub-networks through triple attention modules to extract distinct features from underwater images, bolstering the network's robustness and improving generalization capabilities. Within the sub-network, we introduce a Multi-level Sub-network (MSN) that spans multiple resolution streams, combining contextual information from various scales while preserving the original underwater images' high-resolution spatial details. Comprehensive experiments on multiple underwater datasets demonstrate that CNMS outperforms state-of-the-art methods in image enhancement tasks.

Multiscale levels CO2 decouple reinforcement in China.

Decoupling economic growth from CO2 emissions is imperative for China. Meanwhile, establishing a consistent and comprehensive decoupling inventory that includes national (N), regional and provincial (RP), and city and county (CC) levels is essential for further policy formulation. This research aims to investigate the decoupling status using the "N-RP-CC" approach while considering changes in decoupling trends at the different levels. A combination of the Tapio decoupling model and cluster analysis is employed to study the decoupling's spatiotemporal characteristics and trends. The study first calculates the decoupling value for "national, 7; regions, 30; provinces, 1501 CCs" in China, 2006-2017. The results show that there continues to be an improvement in the decoupling trend at the national level. Conversely, the regional scale exhibits a more vulnerable decoupling trend compared to the national level, with weak and extended negative decoupling observed in northeastern and northern China. Moreover, provincial heterogeneities are increasingly evident, with poor decoupling statuses appearing in Jilin, Heilongjiang, Liaoning, and Xinjiang, as well as many central provinces. Additionally, although more than half of CCs exhibit weak decoupling during most years, seven different states of decoupling were also identified during the time frame. These findings further indicate that spatiotemporal heterogeneities extend beyond RP scales within CCs. Taking the Yangtze River as a boundary line reveals a severe situation in northern areas along with rapid development trends observed in southern regions. Finally, we clustered 1414 CCs based on their industrial proportions for 2017 which further highlights increasingly prominent heterogeneities that should be carefully considered. Based on these findings, policy recommendations such as spatial organization and optimization and technique investment are proposed to achieve CO2 emission decoupling under the N-RP-CC levels.

Dual-path joint correction network for underwater image enhancement.

Acquired underwater images often suffer from severe quality degradation, such as color shift and detail loss due to suspended particles' light absorption and scattering. In this paper, we propose a Dual-path Joint Correction Network (DJC-NET) to cope with the above degenerate issues, preserving different unique properties of underwater images in a dual-branch way. The design of the light absorption correction branch is to improve the selective absorption of light in water and remove color distortion, while the light scattering correction branch aims to improve the blur caused by scattering. Concretely, in the light absorption correction path, we design the triplet color feature extraction module, which balances the triplet color distribution of the degraded image through independent feature learning between R, G, and B channels. In the light scattering correction path, we develop a dual dimensional attention mechanism to extract the texture information from the features, aiming to recover sufficient details by more effective feature extraction. Furthermore, our method utilizes the multi-scale U-net to adaptively fusion features from different paths to generate enhanced images. Extensive visual and objective experimental results demonstrate that our method outperforms state-of-the-art methods in various underwater scenes.

Underwater image restoration by red channel compensation and underwater median dark channel prior.

Underwater images often show low contrast, blurring, and color distortion due to the absorption and scattering of light. In contrast to existing underwater image restoration methods, we propose an underwater image restoration method with red channel compensation and blue-green channel restoration. First, a proposed approach relies on the hue and attenuation differences between different color channels of the underwater image to estimate the background light. Then, the red channel is enhanced according to a perfect reflection assumption algorithm. Finally, a new median underwater dark channel prior (MUDCP) is proposed to precisely estimate the blue-green channel transmission map. Experimental results show that our method significantly improves contrast, removes color bias, and preserves more detail than other underwater restoration techniques.

Analyzing the spatio-temporal variation of the CO2 emissions from district heating systems with "Coal-to-Gas" transition: Evidence from GTWR model and satellite data in China.

Understanding the spatio-temporal heterogeneous effects of socioeconomic and meteorological factors on CO2 emissions from combinations of different district heating systems with "Coal-to-Gas" transition can contribute to the development of future low-carbon energy systems that are efficient and effective. This work downscales city-level CO2 emissions to a 3 × 3 km2 gridded level in northern China during 2012 to 2018. By employing the Geographically and Temporally Weighted Regression (GTWR) model, nighttime light (NTL) data are adopted as a proxy of the level of urbanization, and the Temperature-Humidity-Wind (THW) Index is used as a proxy of meteorological factors in the downscaling model. The results show that, for more than 85% of the cities, urbanization significantly enhances the CO2 emissions of district heating systems, while the THW Index shows negative impacts on CO2 emissions. Significant spatial and temporal heterogeneity exists. The grids with the highest CO2 emissions from coal-fired boilers (grids with annual variation >0.59 Gg CO2/year) are mainly located in nonurban areas of the two megacities Beijing and Tianjin and also in the capital cities of each province. Urbanization has larger effects on the CO2 emissions of natural gas-fired boilers than of coal-fired boilers and combined heat and power (CHP). The average growth rate of CO2 emissions of gas-fired boilers in the urban areas of the study regions was approximately 4.7 times that of nonurban areas. The spatio-temporal heterogeneous impacts of urbanization on CO2 emissions should therefore be considered in future discussions of clean heating policies and climate response strategies.

Underwater image restoration via depth map and illumination estimation based on a single image.

For the enhancement process of underwater images taken in various water types, previous methods employ the simple image formation model, thus obtaining poor restoration results. Recently, a revised underwater image formation model (i.e., the Akkaynak-Treibitz model) has shown better robustness in underwater image restoration, but has drawn little attention due to its complexity. Herein, we develop a dehazing method utilizing the revised model, which depends on the scene depth map and a color correction method to eliminate color distortion. Specifically, we first design an underwater image depth estimation method to create the depth map. Subsequently, according to the depth value of each pixel, the backscatter is estimated and removed by the channel based on the revised model. Furthermore, we propose a color correction approach to adjust the global color distribution of the image automatically. Our method only uses a single underwater image as input to eliminate lightwave absorption and scattering influence. Compared with state-of-the-art methods, both subjective and objective experimental results show that our approach can be applied to various real-world underwater scenes and has better contrast and color.

Underwater image restoration via feature priors to estimate background light and optimized transmission map.

Underwater images frequently suffer from color casts and poor contrast, due to the absorption and scattering of light in water medium. To address these two degradation issues, we propose an underwater image restoration method based on feature priors inspired by underwater scene prior. Concretely, we first develop a robust model to estimate the background light according to feature priors of flatness, hue, and brightness, which can effectively relieve color distortion. Next, we compensate the red channel of color corrected image to revise the transmission map of it. Coupled with the structure-guided filter, the coarse transmission map is refined. The refined transmission map preserves the edge information while improving the contrast. Extensive experiments on diverse degradation scenes demonstrate that our method achieves superior performance against several state-of-the-art methods.

Integrated ABR and UASB system for dairy wastewater treatment: Engineering design and practice.

This work designed and assessed the engineering performance of dairy wastewater treatment by an integrated system consisting of an anaerobic baffled reactor (ABR) and an upflow anaerobic sludge blanket (UASB). With fats adsorbed and decomposed, proteins were first denatured coagulated into solids in the ABR treatment process, and this process created suitable conditions for sludge retention in the sludge bed of the UASB. As a result, the combined system achieved a substantial reduction in excess sludge from 3 to 5 t/d to 3 t/m, notable biogas generation, and 98% COD removal, while the other pollutants in the effluent met relevant standards. In addition, the system attained an excellent performance in terms of the energy consumption and water treatment agent amount. Two active plants achieved operation costs lower than 0.5 kW h/t, while stable operations under ambient temperature conditions lasted longer than three years. Engineering practices both technically and economically affirmed the potential of the proposed system for dairy wastewater treatment.

Evaluation of China's Environmental Pressures Based on Satellite NO2 Observation and the Extended STIRPAT Model.

China's rapid urbanization and industrialization have affected the spatiotemporal patterns of nitrogen dioxide (NO2) pollution, which has led to greater environmental pressures. In order to mitigate the environmental pressures caused by NO2 pollution, it is of vital importance to investigate the influencing factors. We first obtained data for NO2 pollution at the city level using satellite observation techniques and analyzed its spatial distribution. Next, we introduced a theoretical framework, an extended stochastic impacts by regression on population, affluence, and technology (STIRPAT) model, to quantify the relationship between NO2 pollution and its contributing natural and socio-economic factors. The results are as follows. Cities with high NO2 pollution are mainly concentrated in the North China Plain. On the contrary, southwestern cities are characterized by low NO2 pollution. In addition, we find that population, per capita gross domestic product, the share of the secondary industry, ambient air pressures, total nighttime light data, and urban road area have a positive impact on NO2 pollution. In contrast, increases in the normalized difference vegetation index (NDVI), relative humidity, temperature, and wind speed may reduce NO2 pollution. These empirical results should help the government to effectively and efficiently implement further emission reductions and energy saving policies in Chinese cities in a bid to mitigate the environmental pressures.

A Space Affine Matching Approach to fMRI Time Series Analysis.

For fMRI time series analysis, an important challenge is to overcome the potential delay between hemodynamic response signal and cognitive stimuli signal, namely the same frequency but different phase (SFDP) problem. In this paper, a novel space affine matching feature is presented by introducing the time domain and frequency domain features. The time domain feature is used to discern different stimuli, while the frequency domain feature to eliminate the delay. And then we propose a space affine matching (SAM) algorithm to match fMRI time series by our affine feature, in which a normal vector is estimated using gradient descent to explore the time series matching optimally. The experimental results illustrate that the SAM algorithm is insensitive to the delay between the hemodynamic response signal and the cognitive stimuli signal. Our approach significantly outperforms GLM method while there exists the delay. The approach can help us solve the SFDP problem in fMRI time series matching and thus of great promise to reveal brain dynamics.

Involvement of spinal microglia and interleukin-18 in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.

Dexmedetomidine, a selective alpha 2-adrenoceptor (α2AR) agonist, has provided significant analgesia in neuropathic pain. However, its underlying molecular mechanism has not been fully elucidated. In the present study, we found that intrathecal administration of dexmedetomidine alleviated mechanical allodynia induced by chronic constriction injury (CCI), and pretreatment with BRL44408 significantly reversed the dexmedetomidine-induced anti-nociceptive effect. Western blotting revealed that dexmedetomidine reduced the activation of microglia and the upregulation of interleukin-18 (IL-18) protein expression in the ipsilateral lumbar spinal dorsal horn, while BRL44408 pretreatment significantly blocked these effects of dexmedetomidine. Immunocytochemistry/immunohistochemistry indicated that the α2A-adrenoceptor was localised to microglia in primary culture, and IL-18 predominantly colocalised with the microglial marker Iba-1 in the dorsal horn of the spinal cord. These results suggest that the IL-18 signalling pathway in microglia may be involved in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.

Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells.

Transcriptional elongation by RNA polymerase II (Pol II) is regulated by positive transcription elongation factor b (P-TEFb) in association with bromodomain-containing protein 4 (BRD4). We used genome-wide chromatin immunoprecipitation sequencing in primary human CD4+ T cells to reveal that BRD4 co-localizes with Ser-2-phosphorylated Pol II (Pol II Ser-2) at both enhancers and promoters of active genes. Disruption of bromodomain-histone acetylation interactions by JQ1, a small-molecule bromodomain inhibitor, resulted in decreased BRD4 binding, reduced Pol II Ser-2, and reduced expression of lineage-specific genes in primary human CD4+ T cells. A large number of JQ1-disrupted BRD4 binding regions exhibited diacetylated H4 (lysine 5 and -8) and H3K27 acetylation (H3K27ac), which correlated with the presence of histone acetyltransferases and deacetylases. Genes associated with BRD4/H3K27ac co-occupancy exhibited significantly higher activity than those associated with H3K27ac or BRD4 binding alone. Comparison of BRD4 binding in T cells and in human embryonic stem cells revealed that enhancer BRD4 binding sites were predominantly lineage-specific. Our findings suggest that BRD4-driven Pol II phosphorylation at serine 2 plays an important role in regulating lineage-specific gene transcription in human CD4+ T cells.

Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats.

BACKGROUND: Spinal glia, particularly microglia and astrocytes, are of the utmost importance in the development and maintenance of chronic pain. A recent study from our laboratory revealed that gabapentin, a recommended first-line treatment for multiple neuropathic conditions, could also efficiently antagonize thermal hyperalgesia evoked by complete Freund's adjuvant (CFA)-induced monoarthritis (MA). In the present study, we investigated whether the spinal glia are involved in the anti-hyperalgesic effect of gabapentin and how this event occurs. RESULTS: Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes. These cells exhibited large cell bodies, thick processes and increases in the ionized calcium binding adapter molecule 1 (Iba-1, a microglial marker) or the glia fibrillary acidic protein (GFAP, an astrocytic marker). These cells also displayed immunoreactive signals, and an upregulation of the voltage-gated calcium channels (VGCCs) α2/δ-1 subunit, CX3CL1 and CX3CR1 expression levels in the spinal cord. These changes were associated with the development of thermal hyperalgesia. Immunofluorescence staining showed that VGCC α2/δ-1 subunit, a proposed gabapentin target of action, was widely distributed in primary afferent fibers terminals and dorsal horn neurons. CX3CL1, a potential trigger to activate microglia, colocalized with VGCC α2/δ-1 subunits in the spinal dorsal horn. However, its receptor CX3CR1 was mainly expressed in the spinal microglia. Multiple intraperitoneal (i.p.) gabapentin injections (100 mg/kg, once daily for 4 days with the first injection 60 min before intra-articular CFA) suppressed the activation of spinal microglia, downregulated spinal VGCC α2/δ-1 subunits decreased CX3CL1 levels and blocked the development of thermal hyperalgesia in MA rats. CONCLUSIONS: Here we provide the first evidence that gabapentin diminishes CX3CL1 signaling and spinal microglia activation induced by joint inflammation. We also show that the VGCC α2/δ-1 subunits might be involved in these events.

Evidence for suppression of spinal glial activation by dexmedetomidine in a rat model of monoarthritis.

1. Spinal glial cells play a key role in developing and maintaining allodynia and hyperalgesia following tissue inflammation. Dexmedetomidine, a highly selective α(2) -adrenoceptor (α(2) -AR) agonist, has exhibited a significant analgesic effect in various rodent models of chronic pain. However, whether spinal glial activation is involved in the analgesic effect of dexmedetomidine remains unknown. The present study investigated whether spinal administration of dexmedetomidine could antagonize glial activation in the spinal dorsal horn and attenuate thermal hyperalgesia in complete Freund's adjuvant (CFA)-induced ankle joint monoarthritic (MA) rats. 2. Unilateral intra-articular injection of CFA produced a robust activation of microglia and astrocytes in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Repeated lumbar puncture (LP) administration of dexmedetomidine (10 µg) significantly attenuated MA-induced thermal hyperalgesia in a cumulative manner. Monoarthritis-induced spinal glial activation was also suppressed following dexmedetomidine application. The α(2A) -AR, essential for the antinociceptive effects of α(2) -AR agonists, was detected in spinal neurons and glia, as well as in dorsal root ganglion primary afferent neurons, which may be implicated in dexmedetomidine-induced suppression of spinal glial activation and antihyperalgesic effects. 3. These data provide the first evidence that blocking spinal glial activation is involved in the analgesic action of dexmedetomidine.

Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis.

AIM: To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (alpha(2)AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis (MA). METHODS: MA was induced by an intra-articular injection of complete Freund's adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting. RESULTS: Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 microg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 microg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. CONCLUSION: Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats.

Administration of midazolam in infancy does not affect learning and memory of adult mice.

1. Midazolam is a common fast-acting GABA(A) receptor agonist. Recent data suggest that exposure to midazolam in early life may cause long-term effects on brain function through stable epigenetic reprogramming. The aim of the present study was to determine whether the administration of midazolam to infant mice would affect their learning and memory in adulthood. 2. An open-field test was conducted before and then 3, 24, 48 and 72 h after administration of midazolam (50 mg/kg, i.p.) to infant mice. Saline control mice received an equal volume of saline i.p. 3 h before the open-field test. Total movements, total movement time, total movement distance and velocity were analysed. Novel object recognition (NOR), Morris water-maze and passive avoidance tests were performed when the treated mice grew to adulthood (105 days of age). 3. The results of open-field test showed that midazolam significantly reduced locomotor activity (total movements, total movement time, total movement distance and velocity) in infant mice 3 and 24 h after drug administration and that these effects had disappeared by 72 h after drug administration. The results of the water-maze, NOR and passive avoidance tests in adulthood (at 105 days of age) indicated that administration of midazolam in infancy had no long-term effects on the learning and memory behaviours of adult mice compared with the saline control. 4. Acute midazolam administration to infant mice affected spontaneous locomotor activity for approximately 2 days, but did not seem to have any significant impact on cognitive functioning that lasted into adulthood.

Antihyperalgesic effect of systemic dexmedetomidine and gabapentin in a rat model of monoarthritis.

The present study investigated the effects of systemic administration of dexmedetomidine, a selective alpha2 adrenergic receptor (alpha2AR) agonist, and gabapentin either alone or in combination on thermal hyperalgesia evoked by ankle joint inflammation. Monoarthritis of rat ankle joint was induced by an intra-articular injection of Complete Freund's Adjuvant (CFA). The paw withdrawal latency (PWL) from a thermal stimulus was measured in awake rats. Intraperitoneal (i.p.) injection of dexmedetomidine (2.5, 5, 10 and 20 microg/kg) or gabapentin (25, 50, 100 and 200 mg/kg) significantly and dose-dependently increased the PWL of the hindpaw ipsilateral to CFA-injected joint. The PWLs of the non-injected and normal saline (NS)-injected hindpaws were not significantly affected by the two agents at the most doses tested except the highest dose of dexmedetomidine (20 microg/kg). Although low dose of dexmedetomidine (2.5 microg/kg) or gabapentin (25 mg/kg) alone did not affect or lightly increased PWLs of the hindpaw ipsilateral to CFA-injected joint, a combination of dexmedetomidine and gabapentin (2.5 microg/kg+25 mg/kg, or 5 microg/kg+50 mg/kg) significantly reversed CFA-induced thermal hyperalgesia for 60 min without sedation/motor impairment. These results provide the first identification that co-application of dexmedetomidine and gabapentin may synergistically antagonize inflammatory pain, and this might prove to be beneficial in the treatment of arthritic pain.

GSK3beta modulates PACAP-induced neuritogenesis in PC12 cells by acting downstream of Rap1 in a caveolae-dependent manner.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neurotrophic peptide. Here, we show that PACAP recruits Rap1 into caveolin-enriched membrane subdomains in PC12 cells and activates Rap1, nuclear ERK1/2, Elk-1 and CREB in a caveolae-dependent manner. We reveal that GSK3beta is a novel modulator in PACAP signalling. PACAP induces phosphorylation of serine 9 in GSK3beta, which is inhibited by silencing Rap1. Lithium and valproate promote but wortmannin and LY294002 attenuate PACAP-induced phosphorylation of both GSK3beta and ERK1/2, whereas MEK inhibitor PD98059 inhibits nerve growth factor- but not PACAP-induced phosphorylation of GSK3beta, suggesting that GSK3beta operates downstream of Rapt 1 but upstream of ERK1/2 in PACAP signalling. Inhibition or stimulation of GSK3beta results in a 2-fold increase and 6-fold decrease in PACAP-induced neurite outgrowth, respectively. These results reveal an important role of caveolae in the signal transduction of PACAP and that GSK3beta is a critical regulator in PACAP-induced neuronal differentiation.