Mechanistic insights into G-protein coupling with an agonist-bound G-protein-coupled receptor.

G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by promoting guanine nucleotide exchange. Here, we investigate the coupling of G proteins with GPCRs and describe the events that ultimately lead to the ejection of GDP from its binding pocket in the Gα subunit, the rate-limiting step during G-protein activation. Using molecular dynamics simulations, we investigate the temporal progression of structural rearrangements of GDP-bound Gs protein (Gs·GDP; hereafter GsGDP) upon coupling to the ß2-adrenergic receptor (ß2AR) in atomic detail. The binding of GsGDP to the ß2AR is followed by long-range allosteric effects that significantly reduce the energy needed for GDP release: the opening of α1-αF helices, the displacement of the αG helix and the opening of the α-helical domain. Signal propagation to the Gs occurs through an extended receptor interface, including a lysine-rich motif at the intracellular end of a kinked transmembrane helix 6, which was confirmed by site-directed mutagenesis and functional assays. From this ß2AR-GsGDP intermediate, Gs undergoes an in-plane rotation along the receptor axis to approach the ß2AR-Gsempty state. The simulations shed light on how the structural elements at the receptor-G-protein interface may interact to transmit the signal over 30 Å to the nucleotide-binding site. Our analysis extends the current limited view of nucleotide-free snapshots to include additional states and structural features responsible for signaling and G-protein coupling specificity.

Band Alignment Transition and Enhanced Performance in Vertical SnS2/MoS2 van der Waals Photodetectors.

The strong light-matter interaction and naturally passivated surfaces of van der Waals materials make heterojunctions of such materials ideal candidates for high-performance photodetectors. In this study, we fabricated SnS2/MoS2 van der Waals heterojunctions and investigated their photoelectric properties. Using an applied gate voltage, we can effectively alter the band arrangement and achieve a transition in type II and type I junctions. It is found that the SnS2/MoS2 van der Waals heterostructures are type II heterojunctions when the gate voltage is above -25 V. Below this gate voltage, the heterojunctions become type I. Photoelectric measurements under various wavelengths of incident light reveal enhanced sensitivity in the ultraviolet region and a broadband sensing range from 400 to 800 nm. Moreover, due to the transition from type II to type I band alignment, the measured photocurrent saturates at a specific gate voltage, and this value depends crucially on the bias voltage and light wavelength, providing a potential avenue for designing compact spectrometers.

The Effects of Unconventional Feed Fermentation on Intestinal Oxidative Stress in Animals.

Unconventional feed, which is abundant in China, contains anti-nutritional factors and toxins; however, these can be greatly reduced with microbial fermentation, thus improving the nutrient content of the feed, enhancing animal appetites, and ultimately significantly improving the intestinal health and growth performance of animals. When oxidative stress occurs, fermented feed can effectively reduce the damage caused by stress to the gastrointestinal tract, accelerate the removal of gastrointestinal abnormalities, improve the ability to resist intestinal stress, and ensure the efficient production of animals. This review introduces the application of unconventional fermented feed in animal production, and expounds upon the function of unconventional fermented feed in animals with oxidative stress symptoms, so as to provide a theoretical reference for the development and application of unconventional fermented feed in antioxidative stress reduction.

Applying deep learning to recognize the properties of vitreous opacity in ophthalmic ultrasound images.

BACKGROUND: To explore the feasibility of artificial intelligence technology based on deep learning to automatically recognize the properties of vitreous opacities in ophthalmic ultrasound images. METHODS: A total of 2000 greyscale Doppler ultrasound images containing non-pathological eye and three typical vitreous opacities confirmed as physiological vitreous opacity (VO), asteroid hyalosis (AH), and vitreous haemorrhage (VH) were selected and labelled for each lesion type. Five residual networks (ResNet) and two GoogLeNet models were trained to recognize vitreous lesions. Seventy-five percent of the images were randomly selected as the training set, and the remaining 25% were selected as the test set. The accuracy and parameters were recorded and compared among these seven different deep learning (DL) models. The precision, recall, F1 score, and area under the receiver operating characteristic curve (AUC) values for recognizing vitreous lesions were calculated for the most accurate DL model. RESULTS: These seven DL models had significant differences in terms of their accuracy and parameters. GoogLeNet Inception V1 achieved the highest accuracy (95.5%) and minor parameters (10315580) in vitreous lesion recognition. GoogLeNet Inception V1 achieved precision values of 0.94, 0.94, 0.96, and 0.96, recall values of 0.94, 0.93, 0.97 and 0.98, and F1 scores of 0.94, 0.93, 0.96 and 0.97 for normal, VO, AH, and VH recognition, respectively. The AUC values for these four vitreous lesion types were 0.99, 1.0, 0.99, and 0.99, respectively. CONCLUSIONS: GoogLeNet Inception V1 has shown promising results in ophthalmic ultrasound image recognition. With increasing ultrasound image data, a wide variety of confidential information on eye diseases can be detected automatically by artificial intelligence technology based on deep learning.

Distinct serum GDNF coupling with brain structural and functional changes underlies cognitive status in Parkinson's disease.

AIM: Aberrations in brain connections are implicated in the pathogenesis of Parkinson's disease (PD). We previously demonstrated that Glial cell-derived neurotrophic factor (GDNF) reduction is associated with cognition decline. Nonetheless, it is elusive if the pattern of brain topological connectivity differed across PD with divergent serum GDNF levels, and the accompanying profile of cognitive deficits has yet to be determined. METHODS: We collected data on the participants' cognition, demographics, and serum GDNF levels. Participants underwent 3.0T magnetic resonance imaging, and we assessed the degree centrality, brain network topology, and cortical thickness of the healthy control (HC) (n = 25), PD-high-GDNF (n = 19), and PD-low-GDNF (n = 19) groups using graph-theoretic measures of resting-state functional MRI to reveal how much brain connectivity varies and its clinical correlates, as well as to determine factors predicting the cognitive status in PD. RESULTS: The results show different network properties between groups. Degree centrality abnormalities were found in the right inferior frontal gyrus and right parietal lobe postcentral gyrus, linked with cognition scores. The two aberrant clusters serve as a potentially powerful signal for determining whether a patient has PD and the patient's cognition level after integrating with GDNF, duration, and dopamine dosage. Moreover, we found a significant positive relationship between the thickness of the left caudal middle frontal lobe and a plethora of cognitive domains. Further discriminant analysis revealed that the cortical thickness of this region could distinguish PD patients from healthy controls. The mental state evaluation will also be more precise when paired with GDNF and duration. CONCLUSION: Our findings reveal that the topological features of brain networks and cortical thickness are altered in PD patients with cognitive deficits. The above change, accompanied by the serum GDNF, may have merit as a diagnosis marker for PD and, arguably, cognition status.

Dehydrin CaDHN2 Enhances Drought Tolerance by Affecting Ascorbic Acid Synthesis under Drought in Peppers.

Peppers (Capsicum annuum L.), as a horticultural crop with one of the highest ascorbic acid contents, are negatively affected by detrimental environmental conditions both in terms of quality and productivity. In peppers, the high level of ascorbic acid is not only a nutrient substance but also plays a role in environmental stress, i.e., drought stress. When suffering from drought stress, plants accumulate dehydrins, which play important roles in the stress response. Here, we isolated an SK3-type DHN gene CaDHN2 from peppers. CaDHN2 was located in the nucleus, cytoplasm, and cell membrane. In CaDHN2-silenced peppers, which are generated by virus-induced gene silencing (VIGS), the survival rate is much lower, the electrolytic leakage is higher, and the accumulation of reactive oxygen species (ROS) is greater when compared with the control under drought stress. Moreover, when CaDHN2 (CaDHN2-OE) is overexpressed in Arabidopsis, theoverexpressing plants show enhanced drought tolerance, increased antioxidant enzyme activities, and lower ROS content. Based on yeast two-hybrid (Y2H), GST-pull down, and bimolecular fluorescence complementation (BiFC) results, we found that CaDHN2 interacts with CaGGP1, the key enzyme in ascorbic acid (AsA) synthesis, in the cytoplasm. Accordingly, the level of ascorbic acid is highly reduced in CaDHN2-silenced peppers, indicating that CaDHN2 interacts with CaGGP1 to affect the synthesis of ascorbic acid under drought stress, thus improving the drought tolerance of peppers. Our research provides a basis for further study of the function of DHN genes.

Identification of potentially functional circRNAs and prediction of the circRNA-miRNA-hub gene network in mice with primary blast lung injury.

OBJECTIVES: Primary blast lung injury (PBLI) is the main cause of death in blast injury patients, and is often ignored due to the absence of a specific diagnosis. Circular RNAs (circRNAs) are becoming recognized as new regulators of various diseases, but the role of circRNAs in PBLI remain largely unknown. This study aimed to investigate PBLI-related circRNAs and their probable roles as new regulators in PBLI in order to provide new ideas for PBLI diagnosis and treatment. METHODS: The differentially expressed (DE) circRNA and mRNA profiles were screened by transcriptome high-throughput sequencing and validated by quantitative real-time PCR (qRT-PCR). The GO and KEGG pathway enrichment was used to investigate the potential function of DE mRNAs. The interactions between proteins were analyzed using the STRING database and hub genes were identified using the MCODE plugin. Then, Cytoscape software was used to illustrate the circRNA-miRNA-hub gene network. RESULTS: A total of 117 circRNAs and 681 mRNAs were aberrantly expressed in PBLI, including 64 up-regulated and 53 down-regulated circRNAs, and 315 up-regulated and 366 down-regulated mRNAs. GO and KEGG analysis revealed that the DE mRNAs might be involved in the TNF signaling pathway and Fanconi anemia pathway. Hub genes, including Cenpf, Ndc80, Cdk1, Aurkb, Ttk, Aspm, Ccnb1, Kif11, Bub1 and Top2a, were obtained using the MCODE plugin. The network consist of 6 circRNAs (chr18:21008725-21020999 + , chr4:44893533-44895989 + , chr4:56899026-56910247-, chr5:123709382-123719528-, chr9:108528589-108544977 + and chr15:93452117-93465245 +), 7 miRNAs (mmu-miR-3058-5p, mmu-miR-3063-5p, mmu-miR-668-5p, mmu-miR-7038-3p, mmu-miR-761, mmu-miR-7673-5p and mmu-miR-9-5p) and 6 mRNAs (Aspm, Aurkb, Bub1, Cdk1, Cenpf and Top2a). CONCLUSIONS: This study examined a circRNA-miRNA-hub gene regulatory network associated with PBLI and explored the potential functions of circRNAs in the network for the first time. Six circRNAs in the circRNA-miRNA-hub gene regulatory network, including chr18:21008725-21020999 + , chr4:44893533-44895989 + , chr4:56899026-56910247-, chr5:123709382-123719528-, chr9:108528589-108544977 + and chr15:93452117-93465245 + may play an essential role in PBLI.

Edaravone dexborneol ameliorates cognitive impairment by regulating the NF-κB pathway through AHR and promoting microglial polarization towards the M2 phenotype in mice with bilateral carotid artery stenosis (BCAS).

Cerebral small vessel disease (CSVD) is one of the most important causes of stroke and vascular dementia, so exploring effective treatment modalities for CSVD is warranted. This study aimed to explore the anti-inflammatory effects of Edaravone dexborneol (C.EDA) in a CSVD model. Mice with CSVD showed distinct cognitive decline, as assessed by the Morris water maze (MWM). Pathological staining verified leakage across the blood‒brain barrier (BBB), microglial proliferation, neuronal loss and demyelination. Western blot analysis demonstrated that M1 microglia dominated prophase and released proinflammatory molecules; the aryl hydrocarbon receptor (AHR) was found to participate in modulating nuclear factor-kappa B (NF-κB) signalling activation through tumour necrosis factor receptor-associated factor-6 (TRAF6). C.EDA treatment resulted in the polarization of microglia from the M1 to the M2 phenotype. Mice sequentially treated with C.EDA exhibited a significant improvement in cognitive function; expression of the anti-inflammatory cytokines and modulatory proteins AHR and TRAF6 was upregulated, while the levels of pNF-κBp65 and pIΚBα were downregulated. C.EDA promoted microglial activation towards the M2 phenotype by upregulating AHR expression, which prevented TRAF6 ubiquitination, promoted NF-κB RelA/p65 protein degradation and inhibited subsequent NF-κB phosphorylation. Mechanistically, the anti-inflammatory effect of C.EDA alleviated neuronal loss and myelin damage, while at the functional level, C.EDA improved cognitive function and thus showed good application prospects.

Scattering direction sampling methods for polarized Monte Carlo simulation of oceanic lidar.

Monte Carlo techniques have been widely applied in polarized light simulation. Based on different preconditions, there are two main types of sampling strategies for scattering direction: one is the scalar sampling method; the others are polarized sampling approaches, including the one- and two-point rejection methods. The polarized simulation of oceanic lidar involves a variety of mediums, and an efficient scattering sampling method is the basis for the coupling simulation of the atmosphere and ocean. To determine the optimal scattering sampling method for oceanic lidar simulation, we developed a polarized Monte Carlo model and simulated Mie scattering, Rayleigh scattering, and Petzold average-particle scattering experiments. This simulation model has been validated by comparison with Ramella-Roman's program [Opt. Express13, 4420 (2005)OPEXFF1094-408710.1364/OPEX.13.004420], with differences in reflectance and transmittance Stokes less than 1% in Mie scattering. The simulation results show these scattering sampling methods differ in runtime, scattering angle distributions, and reflectance and transmittance Stokes. Considering the current simulation accuracy of oceanic lidar, the differences in reflectance and transmittance Stokes are acceptable; thus, the runtime becomes the main evaluation factor. The one-point rejection method and scalar sampling method are preferable for the oceanic lidar polarized simulation. Under complex atmosphere-ocean coupling systems, scalar sampling methods may be a better choice since the calculation process of the sampling is independent of the incident Stokes vector.

miR-223: a key regulator of pulmonary inflammation.

Small noncoding RNAs, known as microRNAs (miRNAs), are vital for the regulation of diverse biological processes. miR-223, an evolutionarily conserved anti-inflammatory miRNA expressed in cells of the myeloid lineage, has been implicated in the regulation of monocyte-macrophage differentiation, proinflammatory responses, and the recruitment of neutrophils. The biological functions of this gene are regulated by its expression levels in cells or tissues. In this review, we first outline the regulatory role of miR-223 in granulocytes, macrophages, endothelial cells, epithelial cells and dendritic cells (DCs). Then, we summarize the possible role of miR-223 in chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), coronavirus disease 2019 (COVID-19) and other pulmonary inflammatory diseases to better understand the molecular regulatory networks in pulmonary inflammatory diseases.

Crosstalk between Inflammation and Hemorrhage/Coagulation Disorders in Primary Blast Lung Injury.

Primary blast lung injury (PBLI), caused by exposure to high-intensity pressure waves from explosions in war, terrorist attacks, industrial production, and life explosions, is associated with pulmonary parenchymal tissue injury and severe ventilation insufficiency. PBLI patients, characterized by diffused intra-alveolar destruction, including hemorrhage and inflammation, might deteriorate into acute respiratory distress syndrome (ARDS) with high mortality. However, due to the absence of guidelines about PBLI, emergency doctors and rescue teams treating PBLI patients rely on experience. The goal of this review is to summarize the mechanisms of PBLI and their cross-linkages, exploring potential diagnostic and therapeutic targets of PBLI. We summarize the pathophysiological performance and pharmacotherapy principles of PBLI. In particular, we emphasize the crosstalk between hemorrhage and inflammation, as well as coagulation, and we propose early control of hemorrhage as the main treatment of PBLI. We also summarize several available therapy methods, including some novel internal hemostatic nanoparticles to prevent the vicious circle of inflammation and coagulation disorders. We hope that this review can provide information about the mechanisms, diagnosis, and treatment of PBLI for all interested investigators.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson's disease.

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson's disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson's disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson's disease. We then established a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson's disease.

MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an overactivated inflammatory response caused by direct or indirect injuries that destroy lung parenchymal cells and dramatically reduce lung function. Although some research progress has been made in recent years, the pathogenesis of ALI/ARDS remains unclear due to its heterogeneity and etiology. MicroRNAs (miRNAs), a type of small noncoding RNA, play a vital role in various diseases. In ALI/ARDS, miRNAs can regulate inflammatory and immune responses by targeting specific molecules. Regulation of miRNA expression can reduce damage and promote the recovery of ALI/ARDS. Consequently, miRNAs are considered as potential diagnostic indicators and therapeutic targets of ALI/ARDS. Given that inflammation plays an important role in the pathogenesis of ALI/ARDS, we review the miRNAs involved in the inflammatory process of ALI/ARDS to provide new ideas for the pathogenesis, clinical diagnosis, and treatment of ALI/ARDS.

A novel animal model of primary blast lung injury and its pathological changes in mice.

BACKGROUND: Primary blast lung injury (PBLI) is a major cause of death in military conflict and terrorist attacks on civilian populations. However, the mechanisms of PBLI are not well understood, and a standardized animal model is urgently needed. This study aimed to establish an animal model of PBLI for laboratory study. METHODS: The animal model of PBLI was established using a self-made mini shock tube simulation device. In brief, mice were randomly divided into two groups: the control group and the model group, the model group were suffered 0.5 bar shock pressures. Mice were sacrificed at 2 hours, 4 hours, 6 hours, 12 hours, and 24 hours after injury. Lung tissue gross observation, hematoxylin and eosin staining and lung pathology scoring were performed to evaluated lung tissue damage. Evans blue dye leakage and bronchoalveolar lavage fluid examination were performed to evaluated pulmonary edema. The relative expression levels of inflammation factors were measured by real-time quantitative polymerase chain reaction and Western blotting analysis. The release of neutrophil extracellular traps was observed by immunofluorescence stain. RESULTS: In the model group, the gross observation and hematoxylin and eosin staining assay showed the inflammatory cell infiltration, intra-alveolar hemorrhage, and damaged lung tissue structure. The Evans blue dye and bronchoalveolar lavage fluid examination revealed that the lung tissue permeability and edema was significantly increased after injury. Real-time quantitative polymerase chain reaction and Western blotting assays showed that IL-1ß, IL-6, TNF-α were upregulated in the model group. Immunofluorescence assay showed that the level of neutrophil extracellular traps in the lung tissue increased significantly in the model group. CONCLUSION: The self-made mini shock tube simulation device can be used to establish the animal model of PBLI successfully. Pathological changes of PBLI mice were characterized by mechanical damage and inflammatory response in lung tissue.

Correlation Between Degree of Lens Opacity and the Phacoemulsification Energy Parameters Using Different Imaging Methods in Age-Related Cataract.

Purpose: To compare the correlation between degree of lens opacity and the phacoemulsification energy parameter in patients with age-related cataract as determined by slit lamp, 25-MHz ultrasound biomicroscopy (UBM), and Scheimpflug imaging (Pentacam) and to evaluate the application of these three methods to measuring lens opacification. Methods: This observational study was conducted in 319 patients (381 eyes) with different types of age-related cataract. The average age of patients was 67.3 ± 11.4 years. The degree of lens opacity acquired by slit lamp, 25-MHz UBM, and Pentacam was determined by the Lens Opacity Classification System III (LOCSIII), pixel units calculated by ImageJ, and lens density, respectively. We primarily analyzed and compared the correlation between lens opacity and the cumulative dissipated energy (CDE) values of phacoemulsification. Results: Cortical, nuclear, and posterior subcapsular (PSC) cataracts were evaluated as follows: LOCSIII grades 3.31 ± 1.42, 3.29 ± 1.49, and 0.91 ± 0.83; pixel units 120.91 ± 22.8, 93.2 ± 15.9, and 99.7 ± 13.0; and lens density 51.8 ± 31.2, 21.2 ± 6.10, and 53.3 ± 35.3, respectively. The CDE values were 12.1 ± 12.4, 13.5 ± 9.11, and 3.93 ± 1.96. In cortical cataract, there was a linear correlation among LOCSIII, pixel units, and CDE value (r = 0.560, r = 0.832, and r = 0.582, respectively; both P < 0.05), but lens density had no correlation with other parameters. In nuclear cataract, there was a linear correlation among LOCSIII, lens density, and CDE value (r = 0.747, r = 0.865, and r = 0.906, respectively; both P < 0.05), but pixel units had no correlation with other parameters. In PSC, only pixel units and LOCSIII showed a correlation. Conclusions: The various imaging methods offered different advantages in terms of determining lens opacity, a feature related to types of age-related cataracts. Choosing the most suitable imaging method to evaluate lens opacification based on the type of age-related cataract is important for accurately predicting the phacoemulsification parameters for cataract surgery. Translational Relevance: Determining the appropriate phacoemulsification strategy depends on quantitative analysis of the degree of lens opacity to reduce intraoperative and postoperative complications and to obtain the optimal postoperative visual outcome.

Comparison of the IOLMaster 700 and the Pentacam in the Analysis of the Lens Nuclear Density Before the Cataract Surgery.

Purpose: To evaluate the difference of the lens nuclear density measured before and after mydriasis by using the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany) and the Pentacam Scheimpflug imaging (Pentacam HR, Oculus Incorporation, Wetzlar, Germany) and investigate the relationship between the measurement data and the phacoemulsification parameters. Methods: Patients with age-related nuclear cataracts diagnosed on the slit-lamp examination were enrolled in the age range of 53-76 years. No patient had a history of ocular surgery, laser treatment, or general disorders affecting vision. The mean optical density (OD) was measured by the IOLMaster 700 by using the Image-Pro® Plus software before and after mydriasis. The Pentacam nucleus densitometry (PND) was obtained automatically from the Pentacam Scheimpflug imaging and compared with OD. The correlation between OD and effective phacoemulsification time (EPT), PND, and EPT were analyzed, respectively. Results: In this study, 53 eyes of 52 patients were evaluated. Before and after mydriasis, the mean OD values were 64.34 ± 23.31 and 63.81 ± 23.21 pixel units, respectively; the mean PND values were 28.51 ± 11.42 and 25.41 ± 11.31, respectively; and the mean EPT value was 6.24 ± 3.49. The Bland-Altman analysis showed that the lens nuclear densities of the two devices were highly consistent. There was no significant difference in the OD values (t = 0.455, p > 0.05) before and after mydriasis, but the difference has existed in the PND values (t = 2.509, p < 0.05). The OD and PND values were positively correlated with EPT before and after mydriasis (r OD-Before = 0.604, r OD-After = 0.593, r PND-Before = 0.701, and r PND-After = 0.891, p < 0.01). Conclusion: The combination of the IOLMaster 700 and the Image-Pro® Plus software can quantitatively evaluate the degree of the cataract lens opacification. It has good consistency with the Pentacam and is positively correlated with the phacoemulsification parameters. It is expected to become a new method to predict the phacoemulsification parameters before and during cataract surgery.

Mechanism of Phosgene-Induced Acute Lung Injury and Treatment Strategy.

Phosgene (COCl2) was once used as a classic suffocation poison and currently plays an essential role in industrial production. Due to its high toxicity, the problem of poisoning caused by leakage during production, storage, and use cannot be ignored. Phosgene mainly acts on the lungs, causing long-lasting respiratory depression, refractory pulmonary edema, and other related lung injuries, which may cause acute respiratory distress syndrome or even death in severe cases. Due to the high mortality, poor prognosis, and frequent sequelae, targeted therapies for phosgene exposure are needed. However, there is currently no specific antidote for phosgene poisoning. This paper reviews the literature on the mechanism and treatment strategies to explore new ideas for the treatment of phosgene poisoning.

Comprehensive serum metabolic and proteomic characterization on cognitive dysfunction in Parkinson's disease.

BACKGROUND: Given the increased incidence of Parkinson's disease (PD) and the lack of accurate early diagnosis of PD with cognitive impairment (PD-CI), we compared the serum metabolomes and proteomes of 26 patients with PD without cognitive impairment (PD-N) and 31 patients with PD-CI by combining grade-dependent proteomics and metabolomics analyses. METHODS: Logistic and linear regression analyses were performed for differential metabolic indicators, cognition, and clinical diagnosis. Ingenuity pathway analysis (IPA) was used to identify metabolites linked to different pathways. Bioinformatics revealed 16 differentially expressed proteins and 32 metabolites. RESULTS: The positive metabolic indicators related to the differential proteins were one sphingolipid, five phosphatidylcholines, and five long-chain fatty acids. The obtained metabolic and proteomics IPA network highlighted the central term of this network was inflammation and abnormal lipid metabolism which are prominent in PD-CI. There was a strong negative correlation between the Mini-Mental State Examination (MMSE)score and LPC (18:1). The receiver operating characteristic (ROC) of LPC (18:1) for PD-N and PD-CI showed that the area under the curve (AUC) value was 0.660 (P=0.039). CONCLUSIONS: In conclusion, serum LPC (18:1) is inversely linked to cognition in PD and presented its potential clinical value in distinguishing the presence or absence of cognitive impairment in PD. The deeper implication of our discovery indicates abnormal lipid metabolism is associated with changes of cognitive status and suggests the potential for possibility of immune system- inflammatory involvement.

Lower GDNF Serum Level Is a Possible Risk Factor for Constipation in Patients With Parkinson Disease: A Case-Control Study.

Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation. Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression. Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD. Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.