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.

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.

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.

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.

Geniposide reduces Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation.

Staphylococcus aureus (S.aureus), a Gram-positive organism, is a frequent cause of subclinical mastitis. Geniposide, an iridoid glucoside isolated from the fruits of Gardenia jasminoides, has been reported to exhibit antibacterial and anti-inflammatory properties. The ability of S. aureus internalizing into bovine mammary epithelial cells (bMEC) has been responsible for the establishment of the bovine mastitis. In this study, we evaluated the effect of geniposide on S. aureus internalization into bMEC and investigated the possible mechanism of action. The results revealed that geniposide (25-100 µg/ml) reduced S. aureus internalization by 17%-67% and down-regulated the mRNA expressions of TAP and BNBD5. Furthermore, geniposide inhibited S.aureus-induced NF-κB activation in a dose-dependent manner. In summary, the potential mechanism of geniposide reducing S. aureus internalization may be by inhibiting NF-κB activation.

A novel CAV derived cell-penetrating peptide efficiently delivers exogenous molecules through caveolae-mediated endocytosis.

Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity. Moreover, CVP1 could successfully deliver ß-glycosidase, poly (I:C) and plasmid into HCT116 cells. Inhibitors and temperature sensitivity analysis further indicated that the cell-penetrating activity of CVP1 was based on ATP-dependent and caveolae-mediated endocytosis. All these data demonstrate that CVP1 has efficient cell-penetrating activity and great potential for developing a novel delivery vector.

Costunolide protects lipopolysaccharide/d-galactosamine-induced acute liver injury in mice by inhibiting NF-κB signaling pathway.

BACKGROUND: Costunolide, a well-known sesquiterpene lactone, has been reported to have anti-inflammatory and anti-oxidative effects. METHODS: In this study, we aim to investigate the protective effects and mechanism of costunolide on lipopolysaccharide/d-galactosamine (LPS/D-Gal)-induced acute liver injury. Acute liver injury animal model was induced by intraperitoneal injection with D-Gal and LPS. Costunolide (10, 20, and 30 mg/kg) was injected intraperitoneally 1 h before or after LPS/D-Gal treatment. RESULTS: The results showed that costunolide significantly attenuated liver pathologic changes, as well as alanine aminotransferase and aspartate aminotransferase levels in serum. Meanwhile, costunolide inhibited the expressions of interleukin (IL-1ß) and tumor necrosis factor (TNF-α) in liver tissues in a dose-dependent manner. Furthermore, costunolide dose dependently inhibited LPS/D-Gal-induced NF-κB activation. CONCLUSIONS: In conclusion, this study suggested that costunolide could attenuate LPS/D-Gal-induced liver injury and might be a potential therapeutic reagent for liver injury.

[Construction of Saccharomyces cerevisiae cell factories for lycopene production].

For microbial production of lycopene, the lycopene synthetic genes from Pantoea agglomerans were integrated into Saccharomyces cerevisiae strain BY4742, to obtain strain ZD-L-000 for production of 0.17 mg · L(-1) lycopene. Improving supplies of isoprenoid precursors was then investigated for increasing lycopene production. Four key genes were chosen to be overexpressed, inclu- ding truncated 3-hydroxy-3-methylglutaryl-CoA reductase gene (tHMG1), which is the major rate-limiting enzyme in the mevalonate (MVA) pathway, a mutated global regulatory factor gene (upc2.1), a fusion gene of FPP synthase (ERG20) and endogenous GGPP synthase (BTS1), which is a key enzyme in the diterpenoid synthetic pathway, and GGPP synthase gene (SaGGPS) from Sulfolobus acidocaldarius. Over-expression of upc2.1 could not improve lycopene production, while over-expression of tHMGI , BTS1-ERG20 and SaGGPS genes led to 2-, 16. 9- and20. 5-fold increase of lycopene production, respectively. In addition, three effective genes, tHMG1, BTS1-ERG20 and SaGGPS, were integrated into rDNA sites of ZD-L-000, resulting in strain ZD-L-201 for production of 13.23 mg · L(-1) lycopene, which was 77-fold higher than that of the parent strain. Finally, two-phase extractive fermentation was performed. The titer of lycopene increased 10-fold to 135.21 mg · L(-1). The engineered yeast strains obtained in this work provided the basis for fermentative production of lycopene.

[Optimization of synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid].

OBJECTIVE: To optimize the synthetic pathway and fermentation process of yeast cell factories for production of oleanoic acid. METHOD: Using the DNA assembler method, one copy of Glycyrrhiza glabra beta-amyrin synthase (GgbAS), Medicago truncatula oleanolic acid synthase (MtOAS) and Arabidopsis thaliana cytochrome P450 reductase 1 (AtCPR1) genes were introduced into Saccharomyces cerevisiae strain BY-OA, resulting in strain BY-20A. YPD medium with different glucose concentration were then used to cultivate strain BY-2OA. RESULT: Increasing gene copies of GgbAS, MtOAS and AtCPR1 resulted in increased beta-amyrin and oleanolic acid production. The strain BY-2OA produced 136.5 mg x L(-1) beta-amyrin and 92.5 mg x L(-1) oleanolic acid, which were 54% and 30% higher than the parent strain BY-OA. Finally, the titer of oleanolic acid increased to 165.7 mg x L(-1) when cultivated in YPD medium with 40 mg x L(-1) glucose. CONCLUSION: Production of oleanoic acid increased significantly in the yeast strain BY-2OA, which can provide the basis for creating an alternative way for production of oleanoic acid in place of extraction from plant sources.

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.

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.

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.

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.

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.

Metabolic engineering of Saccharomyces cerevisiae for production of ginsenosides.

Ginsenosides are the primary bioactive components of ginseng, which is a popular medicinal herb and exhibits diverse pharmacological activities. Protopanaxadiol is the aglycon of several dammarane-type ginsenosides, which also has anticancer activity. For microbial production of protopanaxadiol, dammarenediol-II synthase and protopanaxadiol synthase genes of Panax ginseng, together with a NADPH-cytochrome P450 reductase gene of Arabidopsis thaliana, were introduced into Saccharomyces cerevisiae, resulting in production of 0.05 mg/g DCW protopanaxadiol. Increasing squalene and 2,3-oxidosqualene supplies through overexpressing truncated 3-hydroxyl-3-methylglutaryl-CoA reductase, farnesyl diphosphate synthase, squalene synthase and 2,3-oxidosqualene synthase genes, together with increasing protopanaxadiol synthase activity through codon optimization, led to 262-fold increase of protopanaxadiol production. Finally, using two-phase extractive fermentation resulted in production of 8.40 mg/g DCW protopanaxadiol (1189 mg/L), together with 10.94 mg/g DCW dammarenediol-II (1548 mg/L). The yeast strains engineered in this work can serve as the basis for creating an alternative way for production of ginsenosides in place of extraction from plant sources.

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.

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.

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.

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.

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.