Emergence of an Extensive Drug Resistant Citrobacter portucalensis Clinical Strain Harboring bla SFO-1, bla KPC-2, and bla NDM-1.

Background: To explore the plasmid characteristics and transfer mechanisms of an extensive drug resistant (XDR) clinical isolate, Citrobacter portucalensis L2724hy, co-producing bla SFO-1, bla NDM-1, and bla KPC-2. Methods: Species confirmation of L2724hy was achieved through 16S rRNA sequencing and Average Nucleotide Identity (ANI) analysis. Antimicrobial susceptibility testing (AST) employed the agar dilution and micro broth dilution methods. Identification of resistance genes was carried out by PCR and whole-genome sequencing (WGS). Essential resistance gene locations were verified by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and southern hybridization experiments. Subsequent WGS data analysis delved into drug resistance genes and plasmids. Results: The confirmation of the strain L2724hy as an extensive drug-resistant Citrobacter portucalensis, resistant to almost all antibiotics tested except polymyxin B and tigecycline, was achieved through 16S rRNA sequencing, ANI analysis and AST results. WGS and subsequent analysis revealed L2724hy carrying bla SFO-1, bla NDM-1, and bla KPC-2 on plasmids of various sizes. The uncommon ESBL gene bla SFO-1 coexists with the fosA3 gene on an IncFII plasmid, featuring the genetic environment IS26-fosA3-IS26-ampR-bla SFO-1-IS26. The bla NDM-1 was found on an IncX3 plasmid, coexisting with bla SHV-12, displaying the sequence IS5-IS3000-IS3000-Tn2-bla NDM-1-ble-trpF-dsbD-cutA-gros-groL, lacking ISAa125. The bla KPC-2 is located on an unclassified plasmid, exhibiting the sequence Tn2-tnpR-ISKpn27-bla KPC-2-ISKpn6-korC. Conjugation assays confirmed the transferability of both bla NDM-1 and bla KPC-2. Conclusion: We discovered the coexistence of bla SFO-1, bla NDM-1, and bla KPC-2 in C. portucalensis for the first time, delving into plasmid characteristics and transfer mechanisms. Our finding highlights the importance of vigilant monitoring of drug-resistance genes and insertion elements in uncommon strains.

Paeoniflorigenone inhibits ovarian cancer metastasis through targeting the MUC1/Wnt/ß­catenin pathway.

Ovarian cancer (OC) is one of the most common gynecological malignancies. Currently, chemoradiotherapy is the primary clinical treatment approach for OC; however, it has severe side effects and a high rate of recurrence. Thus, there is an urgent need to develop innovative therapeutic options. Paeoniflorigenone (PFG) is a monoterpene compound isolated from the traditional Chinese medicine Paeoniae Radix Rubra. PFG can inhibit the proliferation of tumor cells; however, its anticancer activity against OC has yet to be elucidated. Mucin 1 (MUC1) is highly expressed in various malignant tumors, and is associated with tumor proliferation, metastasis and epithelial­mesenchymal transition (EMT). In addition, MUC1 affects numerous signaling pathways in tumor cells. In order to develop a possible treatment approach for metastatic OC, the antitumor activity of PFG in OC cells was investigated using Cell Counting Kit­8 assay, Edu assay, flow cytometry, Transwell assay and western blot analysis. In addition, it was assessed how PFG affects MUC1 expression and function. The experiments revealed that PFG significantly inhibited OC cell proliferation, migration, invasion and EMT. PFG also induced S­phase cell cycle arrest in OC cells. Furthermore, PFG inhibited MUC1 promoter activity, which led to a decrease in MUC1 protein expression. By contrast, MUC1 promoted OC progression, including cell proliferation, cell cycle progression and cell migration. Stable knockdown of MUC1 in OC cells improved the ability of PFG to block the Wnt/ß­catenin pathway, and to limit tumor cell invasion and migration, whereas MUC1 overexpression partially counteracted the antitumor effects of PFG. In conclusion, the present study demonstrated that PFG may inhibit the MUC1/Wnt/ß­catenin pathway to induce anti­metastatic, anti­invasive and anti­EMT effects on OC. Notably, MUC1 may be a direct target of PFG. Thus, PFG holds promise as a specific antitumor agent for the treatment of OC.

GLP-1 modulated the firing activity of nigral dopaminergic neurons in both normal and parkinsonian mice.

The spontaneous firing activity of nigral dopaminergic neurons is associated with some important roles including modulation of dopamine release, expression of tyrosine hydroxylase (TH), as well as neuronal survival. The decreased neuroactivity of nigral dopaminergic neurons has been revealed in Parkinson's disease. Central glucagon-like peptide-1 (GLP-1) functions as a neurotransmitter or neuromodulator to exert multiple brain functions. Although morphological studies revealed the expression of GLP-1 receptors (GLP-1Rs) in the substantia nigra pars compacta, the possible modulation of GLP-1 on spontaneous firing activity of nigral dopaminergic neurons is unknown. The present extracellular in vivo single unit recordings revealed that GLP-1R agonist exendin-4 significantly increased the spontaneous firing rate and decreased the firing regularity of partial nigral dopaminergic neurons of adult male C57BL/6 mice. Blockade of GLP-1Rs by exendin (9-39) decreased the firing rate of nigral dopaminergic neurons suggesting the involvement of endogenous GLP-1 in the modulation of firing activity. Furthermore, the PKA and the transient receptor potential canonical (TRPC) 4/5 channels are involved in activation of GLP-1Rs-induced excitatory effects of nigral dopaminergic neurons. Under parkinsonian state, both the exogenous and endogenous GLP-1 could still induce excitatory effects on the surviving nigral dopaminergic neurons. As the mild excitatory stimuli exert neuroprotective effects on nigral dopaminergic neurons, the present GLP-1-induced excitatory effects may partially contribute to its antiparkinsonian effects.

A pollen selection system links self and interspecific incompatibility in the Brassicaceae.

Self-incompatibility and recurrent transitions to self-compatibility have shaped the extant mating systems underlying the nonrandom mating critical for speciation in angiosperms. Linkage between self-incompatibility and speciation is illustrated by the shared pollen rejection pathway between self-incompatibility and interspecific unilateral incompatibility (UI) in the Brassicaceae. However, the pollen discrimination system that activates this shared pathway for heterospecific pollen rejection remains unknown. Here we show that Stigma UI3.1, the genetically identified stigma determinant of UI in Arabidopsis lyrata × Arabidopsis arenosa crosses, encodes the S-locus-related glycoprotein 1 (SLR1). Heterologous expression of A. lyrata or Capsella grandiflora SLR1 confers on some Arabidopsis thaliana accessions the ability to discriminate against heterospecific pollen. Acquisition of this ability also requires a functional S-locus receptor kinase (SRK), whose ligand-induced dimerization activates the self-pollen rejection pathway in the stigma. SLR1 interacts with SRK and interferes with SRK homomer formation. We propose a pollen discrimination system based on competition between basal or ligand-induced SLR1-SRK and SRK-SRK complex formation. The resulting SRK homomer levels would be sensed by the common pollen rejection pathway, allowing discrimination among conspecific self- and cross-pollen as well as heterospecific pollen. Our results establish a mechanistic link at the pollen recognition phase between self-incompatibility and interspecific incompatibility.

Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1.

A triterpenoid isolated from the plant Hedera helix, hederagenin was discovered to have anti-cancer, anti-inflammatory, anti-depressant and anti-fibrosis properties both in vivo and in vitro. In this study, the relationship between mitochondrial fission and hederagenin-induced apoptosis in ovarian cancer (OC) was investigated and the underlying mechanisms were deciphered. Hederagenin's cytotoxicity on OC cells was analyzed using colony formation and CCK-8 assays. The effect of hederagenin on OC cells was also verified by a mouse xenograft tumor model. Flow cytometric analysis was conducted to examine hederagenin's effects on mitochondrial membrane potential, apoptosis, and cell cycle OC cells. MitoTracker Red (CMXRos) staining was performed to observe the mitochondrial morphology. The protein levels of Bak, Bcl-2, Caspase 3, Caspase 9, Cyclin D1 and Bax were measured by Western blot. This study found that hederagenin could suppress the in vivo and in vitro SKOV3 and A2780 cell proliferation in an effective manner. Besides, hederagenin altered the mitochondrial membrane potential, induced S-phase and G0/G1-phase arrest, mitochondrial morphology changes, and apoptosis in OC cells. Additionally, our findings further demonstrated that hederagenin changed the mitochondrial morphology by suppressing dynamin-related protein 1 (Drp1), a crucial mitochondrial division factor. Moreover, Drp1 overexpression could reverse hederagenin-induced apoptosis, whereas the Drp1 knockdown had the opposite effect. Furthermore, hederagenin may trigger BAX mitochondrial translocation and apoptosis in OC cells. These results provided a novel perspective on the relationship between the modulation of mitochondrial morphology and the suppression of ovarian cancer by hederagenin.

Correction: Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFß-Induced EMT in Ovarian Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0168892.].

Monitoring and management of abandoned, lost and discarded fishing gear (ALDFG) in Penghu Islands, Taiwan.

This study investigated the conditions of abandoned, lost, discarded fishing gear (ALDFG) in natural and artificial reef zones and removed it afterward in Penghu Islands. Various feasible suggestions for improving ALDFG management were proposed for the county government to manage and reduce the generation of ALDFG in the future and maintain the marine ecosystem. This study divided the ocean areas of Penghu into five sub-areas for carrying out research and surveys. 165 boat trips of ALDFG investigation and removal were conducted from July 2018 to October 2019. The results show the ALDFG in natural reef areas is mostly large-mesh gillnets (26 %). The rest are single-layer bottom gillnets (21 %) and multi-layer bottom gillnets (20 %). In line with the recent efforts of the Penghu County Government to address ALDFG, it is recommended that the participation of citizen scientists and the promotion of ocean education can be utilized for fishery co-management in Penghu.

Regulation of hPCL3 isoforms' ubiquitination by TRIM21 in non-small cell lung cancer progression.

Non-small cell lung cancer (NSCLC) is the main subtype of lung cancer. The role of hPCL3 isoforms, hPCL3S and hPCL3L, remains ambiguous. This study examines the functional implications of these isoforms in NSCLC, using lung cancer cell lines A549 and NCI-H226c for in vivo and in vitro analyses. The results indicate that elevated expression of both hPCL3S and hPCL3L correlates with diminished overall survival, although only hPCL3S levels are augmented in clinical NSCLC specimens. Inhibition of either isoform leads to reduced cell proliferation, invasion, and migration, with hPCL3S knockdown displaying superior effectiveness. Moreover, the findings reveal that TRIM21 interacts with both isoforms and mediates hPCL3S degradation through K48-linked ubiquitination in NSCLC cells. Conversely, TRIM21 does not facilitate hPCL3L degradation, despite forming K63-linked polyubiquitin chains. These observations highlight the divergent roles of hPCL3 isoforms in NSCLC and underscore the potential therapeutic value of targeting hPCL3S.

Attack Site Density of a Highly-efficient PET Hydrolases.

INTRODUCTION: Poly (ethylene terephthalate) (PET) is one of the most abundant polyester materials used in daily life and it is also one of the main culprits of environmental pollution. ICCG (F243I/D238C/S283C/Y127G) is an enzyme that performs four modifications on the leaf branch compost keratase (LCC). It shows excellent performance in the hydrolysis of PET and has a great potential in further applications. METHOD: Here, we used ICCG to degrade PET particles of various sizes and use the density of attack sites (Γattack) and kinetic parameters to evaluate the effect of particle size on enzyme degradation efficiency. We are surprised to observe that there is a certain relationship between Km and Γattack. In order to further confirm the relationship, we obtained three different enzymes (Y95K, M166S and H218S) by site-directed mutagenesis on the basis of ICCG. RESULT: The results confirmed that there was a negative correlation between Km and Γattack. In addition, we also found that increasing the affinity between the enzyme and the substrate does not necessarily lead to the increase of degradation rate. CONCLUSION: These findings show that the granulation of PET and the selection of appropriate particle size are helpful to improve its industrial application value. At the same time, additional protein engineering to increase ICCG performance is realistic, but it can't be limited to enhance the affinity between enzyme and substrate.

Dissection of Hyperspectral Reflectance to Estimate Photosynthetic Characteristics in Upland Cotton (Gossypium hirsutum L.) under Different Nitrogen Fertilizer Application Based on Machine Learning Algorithms.

Hyperspectral technology has enabled rapid and efficient nitrogen monitoring in crops. However, most approaches involve direct monitoring of nitrogen content or physiological and biochemical indicators directly related to nitrogen, which cannot reflect the overall plant nutritional status. Two important photosynthetic traits, the fraction of absorbed photosynthetically active radiation (FAPAR) and the net photosynthetic rate (Pn), were previously shown to respond positively to nitrogen changes. Here, Pn and FAPAR were used for correlation analysis with hyperspectral data to establish a relationship between nitrogen status and hyperspectral characteristics through photosynthetic traits. Using principal component and band autocorrelation analyses of the original spectral reflectance, two band positions (350-450 and 600-750 nm) sensitive to nitrogen changes were obtained. The performances of four machine learning algorithm models based on six forms of hyperspectral transformations showed that the light gradient boosting machine (LightGBM) model based on the hyperspectral first derivative could better invert the Pn of function-leaves in cotton, and the random forest (RF) model based on hyperspectral first derivative could better invert the FAPAR of the cotton canopy. These results provide advanced metrics for non-destructive tracking of cotton nitrogen status, which can be used to diagnose nitrogen nutrition and cotton growth status in large farms.

Interfacial Engineering of Co3 O4 /Fe2 O3 Nano-Heterostructure Toward Superior Li-O2 Batteries.

A major issue with Li-O2 batteries is their slow oxygen reduction and evolution kinetics, necessitating catalysts with high catalytic activity to improve reaction kinetics and cycle stability. Herein, a nano-heterostructured catalyst composed of Co3 O4 and Fe2 O3 (Co3 O4 /Fe2 O3 ) with a porous rod morphology is achieved through an interfacial engineering strategy by constructing Fe2 O3 on the Co3 O4 surface, which can function as a high-performance cathode in order to efficiently encourage the oxygen reduction and evolution while also reduce the battery polarization during charging and discharging. The density functional theory (DFT) calculations show the differences in charge density at the interface of nano-heterostructures, demonstrating the occurrence of an electron transfer process in the interface region of Co3 O4 and Fe2 O3 , implying a strong electronic coupling transfer, and in turn changing the electronic structure of the Co3 O4 . This significantly reduces the adsorption energy of LiO2 intermediates, thereby effectively lowering the overpotential. The resultant Li-O2 battery has larger discharge specific capacity, lower overpotential for the efficient oxygen evolution/reduction, as well as good cycling stability of 280 cycles. This work demonstrates an effective method to fabricate the nano-heterostrucutred materials with enhanced catalytic efficiency for advanced energy applications.

Emergence of a NDM-1-producing ST25 Klebsiella pneumoniae strain causing neonatal sepsis in China.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) seriously threaten the efficacy of modern medicine with a high associated mortality rate and unprecedented transmission rate. In this study, we isolated a clinical K. pneumoniae strain DY1928 harboring bla NDM-1 from a neonate with blood infection. Antimicrobial susceptibility testing indicated that DY1928 was resistant to various antimicrobial agents, including meropenem, imipenem, ceftriaxone, cefotaxime, ceftazidime, cefepime, piperacillin-tazobactam, and amoxicillin-clavulanate. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE), southern blot and conjugation experiment revealed that the bla NDM-1 gene was located on a conjugative plasmid of IncA/C2 type with a 147.9 kb length. Whole-genome sequencing showed that there was a conservative structure sequence (bla NDM-1-ble-trpF-dsbD) located downstream of the bla NDM-1 gene. Multilocus sequence typing (MLST) classified DY1928 as ST25, which was a hypervirulent K. pneumoniae type. Phylogenetic analysis of genomic data from all ST25 K. pneumoniae strains available in the NCBI database suggested that all bla NDM-1 positive strains were isolated in China and had clinical origins. A mouse bloodstream infection model was constructed to test the virulence of DY1928, and 11 K. pneumoniae strains homologous to DY1928 were isolated from the feces of infected mice. Moreover, we found that DY1928 had a tendency to flow from the blood into the intestine in mice and caused multiple organ damage. To our knowledge, this is the first study to report an infection caused by bla NDM-1-positive ST25 K. pneumoniae in the neonatal unit. Our findings indicated that stricter surveillance and more effective actions were needed to reduce the risk of disseminating such K. pneumoniae strains in clinical settings, especially in neonatal wards.

Network Pharmacology, Molecular Docking, and Experimental Validation to Unveil the Molecular Targets and Mechanisms of Compound Fuling Granule to Treat Ovarian Cancer.

Background: Compound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets. Methods: Significant genes were collected from Therapeutic Target Database and Database of Gene-Disease Associations. The components of CFG were analyzed by LC-MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug-likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein-protein interaction network was prepared using STRING. The ingredient-target network was established using Cytoscape. Molecular docking was performed to visualize the molecule-protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK-8 assay, wound-scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells. Results: A total of 56 bioactive ingredients of CFG and 185 CFG-OC-related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S-transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin-dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways (P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo. DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells. Conclusion: Based on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation.

The Predictive Value of Barthel Score, Sequential Organ Failure Assessment Score, and D-Dimer in the 28-Day Prognosis of Patients with Non-ST Elevation Myocardial Infarction: A Retrospective Study of 358 Patients.

Purpose: To investigate the nursing prediction value of Barthel score, sequential organ failure assessment (SOFA) score and D-dimer on non-ST-elevation myocardial infarction (NSTEMI) inpatients. Methods: The clinical data of 358 NSTEMI patients admitted to the emergency department were analyzed using logistic regression equation and a ROC curve was drawn. The area under ROC curve (AUC) of different indicators was compared. A COX regression model was created, and a survival curve was drawn. Results: There were significant differences in age, D-dimer, WBC, NT-proBNP, EF (%), BI score, MEWS score, and SOFA score between the 28-day death group and the survival group (P < 0.05). The results showed that D-dimer (P = 0.002), SOFA score (P = 0.017), BI score (P < 0.001), and chest pain symptoms (P < 0.001) were independent predictors of 28-day death. When chest pain symptoms (AUC = 0.585), D-dimer (AUC = 0.945, Z = 8.00, P < 0.01), BI score (AUC = 0.145, Z = 5.36, P < 0.01), and SOFA score (AUC = 0.847, Z = 4.93, P < 0.01) were compared, the results showed that BI score (HR = 0.961, P < 0.01) and SOFA score (HR = 1.316, P < 0.001) had statistical significance on the 28-day survival time of the dead patients. Conclusion: The Barthel score, SOFA score, and D-dimer are all essential in predicting the severity of NSTEMI patients, with a high nursing evaluation value. The Barthel and SOFA scores are associated with the risk of death within 28 days.

Exercise Intervention Modulates Synaptic Plasticity by Inhibiting Excessive Microglial Activation via Exosomes.

Background: Exosomes can activate microglia to modulate neural activity and synaptic plasticity by phagocytosis of neural spines or synapses. Our previous research found that an early 4-week exercise intervention in middle cerebral artery occlusion (MCAO) rats can promote the release of exosomes and protect the brain. This study intended to further explore the intrinsic mechanism of neuroprotection by exosome release after exercise. Methods: Rats were randomly divided into four groups: the sham operation (SHAM), middle cerebral artery occlusion (MCAO) with sedentary intervention (SED-MCAO), MCAO with exercise intervention (EX-MCAO), and MCAO with exercise intervention and exosome injection (EX-MCAO-EXO). Modified neurological severity score (mNSS), cerebral infarction volume ratio, microglial activation, dendritic complexity, and expression of synaptophysin (Syn) and postsynaptic density protein 95 (PSD-95) were detected after 28 days of intervention. Results: (1) The exercise improved body weight and mNSS score, and the survival state of the rats after exosome infusion was better. (2) Compared with the SED-MCAO group, the EX-MCAO (P = 0.039) and EX-MCAO-EXO groups (P = 0.002) had significantly lower cerebral infarct volume ratios (P < 0.05), among which the EX-MCAO-EXO group had the lowest (P = 0.031). (3) Compared with the SED-MCAO group, the EX-MCAO and EX-MCAO-EXO groups had a significantly decreased number of microglia (P < 0.001) and significantly increased process length/cell (P < 0.01) and end point/cell (P < 0.01) values, with the EX-MCAO-EXO group having the lowest number of microglia (P = 0.036) and most significantly increased end point/cell value (P = 0.027). (4) Compared with the SED-MCAO group, the total number of intersections and branches of the apical and basal dendrites in the EX-MCAO and EX-MCAO-EXO groups was increased significantly (P < 0.05), and the increase was more significant in the EX-MCAO-EXO group (P < 0.05). (5) The expression levels of Syn and PSD-95 in the EX-MCAO (P Syn = 0.043, P PSD-95 = 0.047) and EX-MCAO-EXO groups were significantly higher than those in the SED-MCAO group (P < 0.05), and the expression levels in the EX-MCAO-EXO group were significantly higher than those in the EX-MCAO group (P < 0.05). Conclusion: Early exercise intervention after stroke can inhibit the excessive activation of microglia and regulate synaptic plasticity by exosome release.

Study on the Correlation between Chinese Medicine Syndrome and Cognitive Dysfunction in Mild Cognitive Impairment.

Objective: To investigate the correlation between Chinese medicine syndrome and cognitive dysfunction in patients with mild cognitive impairment (MCI). Methods: 121 MCI patients were included for syndrome differentiation and syndrome scoring according to the Chinese medicine syndrome classification standard of senile dementia. The cognitive function and cognitive subitems (including visual space and executive function, naming, attention, language, abstraction, delayed recall, and orientation) of patients with different Chinese medicine syndromes were scored with the Montreal Cognitive Assessment (MoCA). Correlation analysis was made on Chinese medicine syndromes and cognitive domain damage. Results: Chinese medicine syndromes from most to least were kidney deficiency and marrow reduction syndrome, turbid phlegm obstructing orifices syndrome, deficiency of heart and spleen syndrome, qi stagnation and blood stasis syndrome, and yin deficiency of heart and liver syndrome. There were no significant differences in MoCA scores among different Chinese medicine syndromes (P > 0.05).In the kidney deficiency and marrow reduction syndrome, the delayed recall score was 1.74 ± 1.23 and the difference was statistically significant when compared with deficiency of heart and spleen syndrome or the yin deficiency of heart and liver syndrome (P < 0.05). In the turbid phlegm obstructing orifices syndrome, the delayed recall score was 1.81 ± 1.33 and the difference was statistically significant when compared with the yin deficiency of heart and liver syndrome (P < 0.05). There was a significant negative correlation between the kidney deficiency and marrow reduction syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.01), and there was a negative correlation between the turbid phlegm obstructing orifices syndrome's Chinese medicine syndrome scores and MoCA scores (P < 0.05). Correlation analysis showed that the kidney deficiency and marrow reduction syndrome was significantly negatively correlated with delayed recall scores (P < 0.01), and it was also negatively correlated with visual space and executive function scores (P < 0.05). The turbid phlegm obstructing orifices syndrome was significantly negatively correlated with delayed recall scores (P < 0.01). Conclusion: The kidney deficiency and marrow reduction syndrome and the turbid phlegm obstructing orifices syndrome were the most common syndromes in MCI. Patients with kidney deficiency and marrow reduction syndrome might have obvious damage in delayed recall function and have damage in visual space and executive function. Patients with turbid phlegm obstructing orifices syndrome might have obvious damage in delayed recall function.

Dexmedetomidine attenuates acute stress-induced liver injury in rats by regulating the miR-34a-5p/ROS/JNK/p38 signaling pathway.

Dexmedetomidine (DEX) protects against acute stress-induced liver injury, but what's less clear lies in the specific mechanism. To elucidate the specific mechanism underlying DEX on acute stress-induced liver injury, an in vivo model was constructed on rats with acute stress-induced liver injury by 15 min of exhaustive swimming and 3 hr of immobilization. DEX (30 µg/kg) or miR-34a-5p agomir was injected into model rats. Open field test was used to verify the establishment of the model. Liver injury was observed by hematoxylin-eosin (H&E) staining. Contents of norepinephrine (NE), alanine aminotransfease (ALT) and aspartate aminotransferase (AST) in serum of rats were detected by enzyme-linked immunosorbent assay (ELISA) and those of oxidative stress markers (reactive oxygen species (ROS), Malondialdehyde (MDA), Glutathione (GSH), Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPX)) were measured using commercial kits. Apoptosis of hepatocytes was detected by Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Western blot was performed to detect the expressions of SOD2, COX-2, cytochrome C, Cleaved caspase 3, Bax, Bcl-2, P-JNK, JNK, P-p38, p38 and c-AMP, p-PKA and PKA in liver tissues. As a result, liver injury in model rat was alleviated by DEX. DEX attenuated the increase in the levels of NE, ALT, AST, MDA, ROS, apoptosis, SOD2, COX-2, Cytochrome C, cleaved caspase 3, Bax, and P-JNK, P-p38, c-AMP, P-PKA and miR-34a-5p, and the decrease in the levels of SOD, GPX, GSH and Bcl-2 in model rats. Furthermore, miR-34a-5p overexpression could partly reverse the effects of DEX. Collectively, DEX could alleviate acute stress-induced liver injury through ROS/JNK/p38 signaling pathway via downregulation of miR-34a-5p.

Investigating the Association between Wake-Up Stroke and Obstructive Sleep Apnea: A Meta-Analysis.

BACKGROUND: Management of wake-up stroke (WUS) is always a challenge as no clear time of onset could be ascertained, and how to choose an appropriate therapy remains unclear. Sleep-disordered breathing (SDB) has been regarded as a potential risk factor to WUS, yet no consensus was achieved. Motivated by the need for a deeper understanding of WUS and its association with sleep apnea, meta-analyses summarizing the available evidence of respiratory events and indices were conducted, and sensitivity analysis was also used for heterogeneity. METHODS: Electronic databases were systematically searched, and cross-checking was done for relevant studies. Collected data included demographic characteristics, and sleep apnea parameters were extracted with stroke patients divided into WUS and NWUS groups. Clinical data of stroke patients accompanied with sleep apnea syndrome (OSA, SAS, and severe SAS) were also extracted for meta-analysis. RESULTS: A total of 13 studies were included in the analysis. The meta-analysis results showed that OSA, SAS, and severe SAS were significantly higher in WUS patients. A significantly higher AHI (WMD 7.74, 95% CI: 1.38-14.11; p = 0.017) and ODI (WMD of 3.85, 95% CI: 0.261-7.438; p = 0.035) than NWUS patients was also observed in the analysis of respiratory indices. CONCLUSION: WUS patients have severer SDB problems compared to NWUS patients suggesting that respiratory events during sleep might be underlying the induction of WUS. Besides, the induction of WUS was significantly associated with men rather than women. Therefore, early diagnosis and management of potential WUS patients should benefit from the detection of SDB status and respiratory effects.

GYY4137 protected the integrity of the blood-brain barrier via activation of the Nrf2/ARE pathway in mice with sepsis.

Injury to the blood-brain barrier (BBB) plays a vital role in sepsis-associated encephalopathy (SAE), which is one of the most common complications of sepsis. GYY4137, a new synthetic compound of hydrogen sulfide (H2 S), has extensive biological benefits. In this study, we focused on the protective effects of GYY4137 on the BBB in septic mice and the underlying mechanisms. The results suggested that whether administrated at the same time or 3 hours after LPS injection, GYY4137 both significantly alleviated the clinical symptoms and the long-term prognosis. Besides, GYY4137 improved the pathological abnormalities of septic mice. Moreover, the degradation of tight junctions in the BBB was considerably inhibited by GYY4137. In addition, GYY4137 significantly attenuated inflammation and apoptosis in the brain. Furthermore, GYY4137 activated the Nrf2/ARE pathway through the sulfhydrylation of Keap1 and inhibited oxidative stress. ML385, the specific inhibitor of Nrf2, significantly reversed the protective effects of GYY4137 in sepsis mice. In conclusion, this study indicated that through the sulfhydrylation of Keap1, GYY4137 activated the Nrf2/ARE pathway and exerted anti-inflammatory, anti-apoptotic and antioxidant effects in septic mice that consequently protected the integrity of the BBB and improved the clinical outcome of sepsis. Our findings suggest that GYY4137 might be a promising agent for the treatment of SAE.