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Delayed neuropsychiatric sequelae (DNS) significantly impact the quality of life in patients following acute carbon monoxide poisoning (COP). This systematic review and meta-analysis aimed to assess the relationship between serum neuron-specific enolase (NSE) levels at admission and the risk of DNS in adults after acute COP. Relevant observational studies with longitudinal follow-up were identified through searches in PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. The random-effects model was used to aggregate results, accounting for potential heterogeneity. Nine cohort studies, including 1501 patients, were analyzed, with 254 (16.9%) developing DNS during follow-up. The pooled data indicated that elevated serum NSE in the early phase was linked to a higher risk of subsequent DNS (odds ratio per 1 ng/mL increase in NSE: 1.10, 95% confidence interval: 1.06 to 1.15, P < 0.001). Moderate heterogeneity (I2 = 46%) among the studies was entirely attributed to one study with the longest follow-up duration (22.3 months; I2 = 0% after excluding this study). Subgroup analyses based on country, study design, sample size, age, sex, admission carboxyhemoglobin levels, DNS incidence, follow-up duration, and quality score yielded consistent results (P for subgroup differences all > 0.05). In summary, high serum NSE levels in the early phase of acute COP are associated with an increased risk of developing DNS during follow-up.

The onset of Alzheimer's disease is related to neuron damage caused by massive deposition of Aβ in the brain. Recent studies suggest that excessive Aβ in the brain mainly comes from peripheral blood, and BBB is the key to regulate Aβ in and out of the brain. In this study, we explored the pathogenesis of AD from the perspective of Aβ transport through the BBB and the effect of QKL injection in AD mice. The results showed that QKL could improve the cognitive dysfunction of AD mice, decrease the level of Aβ and Aβ transporter—RAGE, which was supported by the results of network pharmacology, molecular docking and molecular dynamics simulation. In conclusion, RAGE is a potential target for QKL's therapeutic effect on AD.

Inflammation is a protective stress response triggered by external stimuli, with 5-lipoxygenase (5LOX) playing a pivotal role as a potent mediator of the leukotriene (Lts) inflammatory pathway. Nordihydroguaiaretic acid (NDGA) functions as a natural orthosteric inhibitor of 5LOX, while 3-acetyl-11-keto-β-boswellic acid (AKBA) acts as a natural allosteric inhibitor targeting 5LOX. However, the precise mechanisms of inhibition have remained unclear. In this study, Gaussian accelerated molecular dynamics (GaMD) simulation was employed to elucidate the inhibitory mechanisms of NDGA and AKBA on 5LOX. It was found that the orthosteric inhibitor NDGA was tightly bound in the protein’s active pocket, occupying the active site and inhibiting the catalytic activity of the 5LOX enzyme through competitive inhibition. The binding of the allosteric inhibitor AKBA induced significant changes at the distal active site, leading to a conformational shift of residues 168–173 from a loop to an α-helix and significant negative correlated motions between residues 285–290 and 375–400, reducing the distance between these segments. In the simulation, the volume of the active cavity in the stable conformation of the protein was reduced, hindering the substrate’s entry into the active cavity and, thereby, inhibiting protein activity through allosteric effects. Ultimately, Markov state models (MSM) were used to identify and classify the metastable states of proteins, revealing the transition times between different conformational states. In summary, this study provides theoretical insights into the inhibition mechanisms of 5LOX by AKBA and NDGA, offering new perspectives for the development of novel inhibitors specifically targeting 5LOX, with potential implications for anti-inflammatory drug development.

Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rhesus macaques infected with SHIV1157ipd3N4 for 5 years. One lineage of neutralizing antibodies (JT15 and JT16) targeted the V2-apex in the Env trimers, similar to the J038 lineage bnAbs identified in our previous study. The other lineage neutralizing antibody (JT18) targeted the V3 crown region in the Env, which strongly competed with human 447-52D. Each lineage antibody neutralized a different set of viruses. Interestingly, when the two neutralizing antibodies from different lineages isolated from the same macaque were combined, the mixture had a neutralization breath very similar to that from the cognate sera. Our study demonstrated that a minimum of two different neutralizing antibodies can fully recapitulate the serum neutralization breadth. This observation can have important implications in AIDS vaccine design.

Fourier ptychographic microscopy (FPM) is a computational imaging technology that has endless vitality and application potential in digital pathology. Colored pathological image analysis is the foundation of clinical diagnosis, basic research, and most biomedical problems. However, the current colorful FPM reconstruction methods are time-inefficient, resulting in poor image quality due to optical interference and reconstruction errors. This paper combines coloring and FPM to propose a self-supervised generative adversarial network (GAN) for FPM color reconstruction. We design a generator based on the efficient channel residual (ECR) block to adaptively obtain efficient cross-channel interaction information in a lightweight manner, and we introduce content-consistency loss to learn the high-frequency information of the image and improve the image quality of the staining. Furthermore, the effectiveness of our proposed method is demonstrated through objective indicators and visual evaluations.

To improve the accuracy of non-contact measurements of animal body size and reduce costs, a new monocular camera scanning equipment based on structured light was built with a matched point cloud generation algorithm. Firstly, using the structured light 3D measurement model, the camera intrinsic matrix and extrinsic matrix could be calculated. Secondly, the least square method and the improved segment–facet intersection method were used to implement and optimize the calibration of the light plane. Then, a new algorithm was proposed to extract gray- centers as well as a denoising and matching algorithm, both of which alleviate the astigmatism of light on animal fur and the distortion or fracture of light stripes caused by the irregular shape of an animal’s body. Thirdly, the point cloud was generated via the line–plane intersection method from which animal body sizes could be measured. Finally, an experiment on live animals such as rabbits and animal specimens such as fox and the goat was conducted in order to compare our equipment with a depth camera and a 3D scanner. The result shows that the error of our equipment is approximately 5%, which is much smaller than the error of the other two pieces of equipment. This equipment provides a practicable option for measuring animal body size.

This study is to investigate the effects of dexmedetomidine on myocardial ischemia-reperfusion (I/R) injury and its molecular mechanisms. H9c2 cell injury model was constructed by the hypoxia/normoxia (H/R) conditions. Besides, cAMP response element-binding protein (CREB) overexpression and knockdown cell lines were constructed. Cell viability was determined by cell-counting kit 8. Biochemical assays were used to detect oxidative stress-related biomarkers, cell apoptosis, and ferroptosis-related markers. Our results showed that dexmedetomidine's protective effects on H/R-induced cell damage were reversed by the inhibition of protein kinase A (PKA), CREB, and extracellular signal regulated kinase 1/2 (ERK1/2). Treatment of dexmedetomidine ameliorated oxidative stress in the cardiomyocytes induced by H/R, whereas inhibition of PKA, CREB, or ERK1/2 reversed these protective effects. Cell death including cell necrosis, apoptosis, and ferroptosis was found in the cells under H/R insult. Interestingly, targeting CREB ameliorated ferroptosis and oxidative stress in these cells. In conclusion, dexmedetomidine attenuates myocardial I/R injury by suppressing ferroptosis through the cAMP/PKA/CREB signaling pathway.

Objective: To investigate and predict the targets and signaling pathways of sinomenium acutum (SA) in the treatment of rheumatoid arthritis (RA) through systems biology and network pharmacology, and to elucidate its possible mechanisms of action.Methods: We screened the active ingredients and corresponding target proteins of SA in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN); and obtained the targets of rheumatoid arthritis diseases in a database of gene-disease associations (DisGeNET), Online Mendelian Inheritance in Man (OMIM) database. The two targets were mapped by Venn diagram and the intersection was taken. The intersecting targets were used to construct protein-protein interaction (PPI) network maps in the String database, and Metascape was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, the molecular docking technique was applied to validate and further clarify the core target of SA for the treatment of rheumatoid arthritis.Results: A total of six active ingredients and 217 potential targets were obtained after screening; 2,752 rheumatoid arthritis-related targets and 66 targets common to RA and SA. GO function and KEGG pathway enrichment analysis yielded 751 GO function entries (652 GO biological processes, 59 GO molecular functions and 40 GO cellular components) and 77 KEGG signaling pathways. It mainly involves pathways related to neural activity ligand-receptor interaction pathways, cancer pathways, calcium signaling channels, Th17 cell differentiation and others, which are mainly classified into four categories, including regulation of immunity, anti-inflammation, regulation of cell growth and apoptosis, and signaling. The molecular docking results showed that the binding energy of PTGS2, CASP3, JUN and PPARG to the key components beta-sitosterol, 16-epi-Isositsirikine, Sinomenine and Stepholidine were ≤ −6.5 kcal/mol, suggesting the existence of molecular binding sites.Conclusion: SA acts on key targets such as PTGS2, CASP3, JUN, and PPARG to modulate signaling pathways such as neural activity ligand-receptor interaction, cancer, calcium ion, NF-κB, and Th17 cell differentiation to regulate immunity, anti-inflammation, modulation of cell cycle, bone metabolism, and signaling for the treatment of RA. It was also confirmed that the treatment of RA with SA has multi-component, multi-target, multi-pathway and multi-mechanism characteristics.

The activation of the transient receptor potential ankyrin 1 (TRPA1) channel has anti-fibrotic effects in the lung and intestine. Suburothelial myofibroblasts (subu−MyoFBs), a specialized subset of fibroblasts in the bladder, are known to express TRPA1. However, the role of the TRPA1 in the development of bladder fibrosis remains elusive. In this study, we use the transforming growth factor-β1 (TGF-β1) to induce fibrotic changes in subu−MyoFBs and assess the consequences of TRPA1 activation utilizing RT-qPCR, western blotting, and immunocytochemistry. TGF-β1 stimulation increased α-SMA, collagen type I alpha 1 chain(col1A1), collagen type III (col III), and fibronectin expression, while simultaneously suppressing TRPA1 in cultured human subu−MyoFBs. The activation of TRPA1, with its specific agonist allylisothiocyanate (AITC), inhibited TGF-β1-induced fibrotic changes, and part of these inhibition effects could be reversed by the TRPA1 antagonist, HC030031, or by reducing TRPA1 expression via RNA interference. Furthermore, AITC reduced spinal cord injury-induced fibrotic bladder changes in a rat model. The increased expression of TGF-β1, α-SMA, col1A1 and col III, and fibronectin, and the downregulation of TRPA1, were also detected in the mucosa of fibrotic human bladders. These findings suggest that TRPA1 plays a pivotal role in bladder fibrosis, and the negative cross talk between TRPA1 and TGF-β1 signaling may represent one of the mechanisms underlying fibrotic bladder lesions.

Objective To explore the mechanism behind the faster volitional reaction time (RT) of open skill sports athletes from the perspective of proactive inhibitory control, with the hypothesis that the superior response speed of athletes from open skill sports is related to their enhanced capacity for releasing inhibition. Methods Participants were divided into two groups, an experimental group of 27 table tennis players and a control group of 27 non-athletes. By manipulating cue–target onset asynchrony (CTOA) in a simple cue-target detection task, the timing of target presentation occurred in different phases of the disinhibition process. The time needed for disinhibition were compared between groups. Results For the experimental group, RT varied with CTOA at delays less than 200 ms; for CTOAs greater than 200 ms, RTs were not significantly different. For the control group, RT varied with CTOA for delays as long as 300 ms. Conclusions Table tennis players took less time (200 ms) than non-athletes (300 ms) to complete the disinhibition process, which might partly explain their rapid response speed measured in unpredictable contexts. Significance The study provided evidence for disinhibition speed as a new index to assess the capacity of proactive inhibitory control, and provided a new perspective to explore the superior RT of athletes from open skill sports. We also offered support for the fundamental cognitive benefits of table tennis training.

Summary: Tissue-specific stem cells have unique properties and growth requirements, but a small set of juxtacrine and paracrine signals have been identified that are required across multiple niches. Whereas insulin-like growth factor II (IGF-II) is necessary for prenatal growth, its role in adult stem cell physiology is largely unknown. We show that loss of Igf2 in adult mice resulted in a ∼50% reduction in slowly dividing, label-retaining cells in the two regions of the brain that harbor neural stem cells. Concordantly, induced Igf2 deletion increased newly generated neurons in the olfactory bulb accompanied by hyposmia, and caused impairments in learning and memory and increased anxiety. Induced Igf2 deletion also resulted in rapid loss of stem and progenitor cells in the crypts of Lieberkühn, leading to body-weight loss and lethality and the inability to produce organoids in vitro. These data demonstrate that IGF-II is critical for multiple adult stem cell niches. : In this article, Levison, Wood and colleagues demonstrate that IGF-II expression in the adult mouse is necessary for maintaining multiple adult stem cell niches including in the subventricular and subgranular zones of the brain and in the crypts of Lieberkühn of the gut. Keywords: neural stem cell, IGF-II, intestinal stem cell, subventricular zone, subgranular zone, crypt of Lieberkühn, neurogenesis

Constrained image splicing detection and localization (CISDL) is a newly formulated image forensics task that aims at detecting and localizing the source and forged regions from a series of input suspected image pairs. In this work, we propose a novel Scale-Adaptive Deep Matching (SADM) network for CISDL, consisting of a feature extractor, a scale-adaptive correlation module and a novel mask generator. The feature extractor is built on VGG, which has been reconstructed with atrous convolution. In the scale-adaptive correlation computation module, squeeze-and-excitation (SE) blocks and truncation operations are integrated to process arbitrary-sized images. In the mask generator, an attention-based separable convolutional block is designed to reconstruct richer spatial information and generate more accurate localization results with less parameters and computation burden. Last but not least, we design a pyramid framework of SADM to capture multiscale details, which can increase the detection and localization accuracy of multiscale regions and boundaries. Extensive experiments demonstrate the effectiveness of SADM and the pyramid framework.

Privacy disclosure has become a key challenge in vehicular ad hoc networks (VANETs). Although IEEE, ERSI, etc. suggest that a pseudonym-based scheme is a solution, how to support pseudonym management and vehicle authentication is still an open issue. In this paper, a secure VANETs authentication scheme (PAS) is proposed, where software-defined network (SDN) is integrated as a suitable infrastructure to support anonymous authentication and pseudonym management, while removing the requirement for pseudonym certification in the dynamic VANETs environment. The security and performance analysis indicate that PAS is able protect the privacy of vehicles and has a high efficiency.

Abstract Background Mammalian small intestinal tight junctions (TJ) link epithelial cells to one another and function as a permselective barrier, strictly modulating the passage of ions and macromolecules through the pore and leak pathways, respectively, thereby preventing the absorption of harmful compounds and microbes while allowing regulated transport of nutrients and electrolytes. Small intestinal epithelial permeability is ascribed primarily to the properties of TJs between adjoining enterocytes (ENTs), because there is almost no information on TJ composition and the paracellular permeability of nonenterocyte cell types that constitute a small but significant fraction of the intestinal epithelia. Results Here we directed murine intestinal crypts to form specialized organoids highly enriched in intestinal stem cells (ISCs), absorptive ENTs, secretory goblet cells, or Paneth cells. The morphological and morphometric characteristics of these cells in organoids were similar to those in vivo. The expression of certain TJ proteins varied with cell type: occludin and tricellulin levels were high in both ISCs and Paneth cells, while claudin-1, -2, and -7 expression was greatest in Paneth cells, ISCs, and ENTs, respectively. In contrast, the distribution of claudin-15, zonula occludens 1 (ZO-1), and E-cadherin was relatively homogeneous. E-cadherin and claudin-7 marked mainly the basolateral membrane, while claudin-2, ZO-1, and occludin resided in the apical membrane. Remarkably, organoids enriched in ENTs or goblet cells were over threefold more permeable to 4 and 10 kDa dextran compared to those containing stem and Paneth cells. The TJ-regulator larazotide prevented the approximately tenfold increases in dextran flux induced by the TJ-disrupter AT1002 into organoids of different cell types, indicating that this ZO toxin nonselectively increases permeability. Forced dedifferentiation of mature ENTs results in the reacquisition of ISC-like characteristics in TJ composition and dextran permeability, suggesting that the post-differentiation properties of TJs are not hardwired. Conclusions Differentiation of adult intestinal stem cells into mature secretory and absorptive cell types causes marked, but potentially reversible, changes in TJ composition, resulting in enhanced macromolecular permeability of the TJ leak pathway between ENTs and between goblet cells. This work advances our understanding of how cell differentiation affects the paracellular pathway of epithelia.

To study the influence of different mix proportions on the fresh properties of wet shotcrete, the rheological properties and air content of wet shotcrete with different admixtures before pumping were measured. In addition, the pressure drop along the pipeline and the build-up thickness were studied, and the relationship between the rheological properties and the pumpability and sprayability was discussed. This paper attempts to reveal the influence mechanism of admixtures on the fluidity of wet shotcrete by means of pictures. The results show that free paste effect and ball effect are two key factors that affect the performance of fresh wet shotcrete. Air-entraining agent and fly ash are commonly used admixtures, which improve the pumping performance and spraying performance. Finally, the mix proportions of wet shotcrete are put forward to meet the requirements of different types of shotcrete.

Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT) by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice) as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells. As such, this review aims to highlight the potential clinical benefits of various armed antibody-based immunotherapies, including PDT, as alternative approaches for the treatment of metastatic melanoma.

Phase measuring deflectometry has been widely studied as a way of obtaining the three-dimensional shape of specular objects. Recently, a new direct phase measuring deflectometry technique has been developed to measure the three-dimensional shape of specular objects that have discontinuous and/or isolated surfaces. However, accurate calibration of the system parameters is an important step in direct phase measuring deflectometry. This paper proposes a new calibration method that uses phase information to obtain the system parameters. Phase data are used to accurately calibrate the relative orientation of two liquid crystal display screens in a camera coordinate system, by generating and displaying horizontal and vertical sinusoidal fringe patterns on the two screens. The results of the experiments with an artificial specular step and a concave mirror showed that the proposed calibration method can build a highly accurate relationship between the absolute phase map and the depth data.

The vast majority of gaseous chemical substances exhibit fundamental rovibrational absorption bands in the mid-infrared spectral region (2.5–25 μm), and the absorption of light by these fundamental bands provides a nearly universal means for their detection. A main feature of optical techniques is the non-intrusive in situ detection of trace gases. We reviewed primarily mid-infrared tunable laser-based broadband absorption spectroscopy for trace gas detection, focusing on 2008–2018. The scope of this paper is to discuss recent developments of system configuration, tunable lasers, detectors, broadband spectroscopic techniques, and their applications for sensitive, selective, and quantitative trace gas detection.

To determine the effects of heat-killed VSL#3 (B. breve, B. longum and B. infantis; L. plantarum, L. bulgaricus, L. casei and L. acidophilus; S. salivarius subsp. thermophilus) therapy in the dextran sulfate sodium (DSS)-induced acute experimental colitis in rats. Acute experimental colitis was induced in rats by 5% DSS and freely drink for seven days. Beginning on Day 8, rats underwent gavage once daily for seven days with heat-killed probiotic VSL#3 (0.6 g/kg/day), colonic damage was evaluated histologically and biochemically seven days after gavage. Expression of inflammatory related mediators (STAT3, P-STAT3) and cytokines (IL-6, IL-23, TGFβ) in colonic tissue were detected. The results revealed that heat-killed and live VSL#3 have identical anti-inflammatory properties by the assessed DAI (disease activity index), colon length, histological tissue and MPO activity. Heat-killed and live VSL#3 results in reduced IL-6, IL-23, TGFβ, STAT3 and P-STAT3 expression in colonic tissue. Heat-killed and live VSL#3 have showed the similar anti-inflammatory activity by inhibiting IL-6/STAT3 pathway in the DSS-induced acute experimental colitis in rats.

This protocol describes the procedure of visualizing secreted Wnt5 protein in serum free media via western blotting. This procedure can also be used to visualize other secreted proteins larger than 10,000 daltons. The work presented in this paper visualizes Wnt5 secreted by mouse embryonic fibroblast (MEF), but can be adapted to other cell lines including those transiently transfected by plasmids.

A series of natural photoactive dyes, named as D1–D6 were successfully extracted from six kinds of plant leaves for solar cells. The photoelectrical properties of dyes were measured via UV-Vis absorption spectra, cyclic voltammetry as well as photovoltaic measurement. To theoretically reveal the experimental phenomena, the chlorophyll was selected as the reference dye, where the ground and excited state properties of chlorophyll were calculated via density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The experimental results show that the absorption peaks of those dyes are mainly distributed in the visible light regions of 400–420 nm and 650–700 nm, which are consistent with the absorption spectrum of chlorophyll. The photoelectrical conversion efficiencies of the solar cells sensitized by the six kinds of natural dyes are in the order of D1 > D4 > D2 > D5 > D6 > D3. The dye D1 performance exhibits the highest photoelectrical conversion efficiency of 1.08% among the investigated six natural dyes, with an open circuit voltage of 0.58 V, a short-circuit current density of 2.64 mA cm−2 and a fill factor of 0.70.

Dyes D35 and XY1 for solar cells have been investigated theoretically with the quantum chemistry method and visualized 3D cube representation. Some important information (such as absorption spectra, molecular orbitals, reorganization energy, chemical reactivity, driving force of electron injection, light-harvesting efficiency, as well as the dipole moment, etc.) has been studied to explain the efficiency of dyes, and the visualized intramolecular and intermolecular charge transfer process and fast dynamic process of the interface electron transfer have been studied to estimate the strength of electron transfer in cosensitization. Calculated results indicated that the improved absorption spectra range, fast electron injection, and the larger dipole moment significantly promote the cosensitized solar cell efficiency in comparison with isolated Dye-Sensitized Solar Cells (DSSCs).

Modulating the chlorophyll a (Chl-a) fluorescence by all-trans-β-Carotene (β-Car) in the polarity and non-polarity solutions was investigated. The fluorescence intensity of Chl-a decreased as the concentration of β-Car increased. The excited electronic levels of Chl-a and β-Car became much closer owing to the solvent effect, which led to the electron transfer between both two molecules. A electron-separated pair Chl−·Chl+ that is not luminous was formed due to electron transfer. The solution of Chl-a and β-car in C3H6O was similar to the internal environment of chloroplast. We conclude that the polar solvent is good for the fluorescent modulation in photosystem II.