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ObjectiveThe study investigated the correlation and predictive value between the severity of cerebral microbleeds (CMBs) and the level of serum High Mobility Group Protein B1 (HMGB1) and the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD).MethodsA total of 139 patients with CSVD admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected as study subjects. The Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function and was divided into the cognitive impairment group and the cognitive normal group. Magnetic Resonance Imaging (MRI) and Susceptibility Weighted Imaging (SWI) were used to screen and assess the severity of CMBs. Serum HMGB1 levels of CSVD patients were measured by enzyme linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was used to explore risk factors for cognitive impairment and CMBs. Pearson correlation analysis was used to investigate the correlation between HMGB1 and cognitive function. Receiver Operating Characteristics (ROC) curves were used to assess the predictive value of HMGB1 for the occurrence of cognitive impairment in patients with CMBs.ResultsHigh Mobility Group Protein B1, uric acid (UA), glycosylated hemoglobin (HbA1c), CMBs, lacunar cerebral infarction (LI), years of education, and history of hypertension were risk factors for cognitive impairment (P < 0.05); HMGB1 was significantly and negatively associated with total MoCA score, visuospatial/executive ability, and delayed recall ability (P < 0.05). HMGB1 was significantly and positively correlated with the number of CMBs (P < 0.05). The area under the ROC curve for HMGB1 predicting cognitive impairment in patients with CMBs was 0.807 (P < 0.001).ConclusionSerum HMGB1 levels are associated with the development of cognitive impairment in CSVD patients, and serum HMGB1 levels have a high predictive value for the development of cognitive impairment in CSVD patients with combined CMBs, which can be used for early clinical identification and intervention of vascular cognitive impairment.

Cerebral small vascular disease (CSVD) is a common type of cerebrovascular disease, and an important cause of vascular cognitive impairment (VCI) and stroke. The disease burden is expected to increase further as a result of population aging, an ongoing high prevalence of risk factors (e.g., hypertension), and inadequate management. Due to the poor understanding of pathophysiology in CSVD, there is no effective preventive or therapeutic approach for CSVD. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that is related to the occurrence and development of vascular dysfunction diseases. Therefore, MIF may contribute to the pathogenesis of CSVD and VCI. Here, reviewed MIF participation in chronic cerebral ischemia-hypoperfusion and neurodegeneration pathology, including new evidence for CSVD, and its potential role in protection against VCI.

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features—intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.

GLT-1, the major glutamate transporter in the mammalian central nervous system, is expressed in presynaptic terminals that use glutamate as a neurotransmitter, in addition to astrocytes. It is widely assumed that glutamate homeostasis is regulated primarily by glutamate transporters expressed in astrocytes, leaving the function of GLT-1 in neurons relatively unexplored. We generated conditional GLT-1 knockout (KO) mouse lines to understand the cell-specific functions of GLT-1. We found that stimulus-evoked field extracellular postsynaptic potentials (fEPSPs) recorded in the CA1 region of the hippocampus were normal in the astrocytic GLT-1 KO but were reduced and often absent in the neuronal GLT-1 KO at 40 weeks. The failure of fEPSP generation in the neuronal GLT-1 KO was also observed in slices from 20 weeks old mice but not consistently from 10 weeks old mice. Using an extracellular FRET-based glutamate sensor, we found no difference in stimulus-evoked glutamate accumulation in the neuronal GLT-1 KO, suggesting a postsynaptic cause of the transmission failure. We hypothesized that excitotoxicity underlies the failure of functional recovery of slices from the neuronal GLT-1 KO. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist MK801, when present in the ACSF during the recovery period following cutting of slices, promoted full restoration of fEPSP generation. The inclusion of an enzymatic glutamate scavenging system in the ACSF conferred partial protection. Excitotoxicity might be due to excess release or accumulation of excitatory amino acids, or to metabolic perturbation resulting in increased vulnerability to NMDA receptor activation. Previous studies have demonstrated a defect in the utilization of glutamate by synaptic mitochondria and aspartate production in the synGLT-1 KO in vivo, and we found evidence for similar metabolic perturbations in the slice preparation. In addition, mitochondrial cristae density was higher in synaptic mitochondria in the CA1 region in 20–25 weeks old synGLT-1 KO mice in the CA1 region, suggesting compensation for loss of axon terminal GLT-1 by increased mitochondrial efficiency. These data suggest that GLT-1 expressed in presynaptic terminals serves an important role in the regulation of vulnerability to excitotoxicity, and this regulation may be related to the metabolic role of GLT-1 expressed in glutamatergic axon terminals.

MicroRNAs (miRNAs) are involved in human glioblastoma (GB). MiR-935 has been reported to have both tumor-inhibiting and tumorigenesis effects, but its role in GB remains unclear. Because of the high mortality and morbidity associated with the malignancy of GB, a deeper understanding of the molecular crosstalk that occurs in GB is needed to identify new potential targets for treatment. At present, the mechanism of GB at the molecular level is not fully understood. With the aid of bioinformatic analysis, miR-935 was significantly downregulated in GB, and it presented a poorer outcome. In the glioma cell line and in the nude mice model, the miR-935 inhibited cell proliferation by modulating cell circles in vitro and in vivo. Then, the target genes of miR-935 were analyzed by using the online database, and the direct binding was tested with a luciferase analysis. FZD6 was found to be the direct target of miR-935. The effect of miR-935 was recovered by the overexpression of FZD6 in vitro. In addition, the negative correlation of miR-935 and the expression of FZD6 were confirmed in our clinical samples, and the expression of FZD6 has a strong correlation with tumor malignancy and prognosis. This study showed that miR-935 directly inhibited the expression of FZD6 and inhibited the cell proliferation, thereby suppressing the development of GB, suggesting that miR-935 is a cancer suppressor miRNA and may become a prognostic biomarker or a promising potential therapeutic target for human GBs.

The development of land subsidence has seriously affected the safe operation of Beijing-Tianjin high-speed railway. The South-to-North Water Diversion Project Central Route (SNWDP-CR) was officially put into operation in December 2014. It has changed the water supply pattern in Beijing and provided conditions for reducing groundwater exploitation and controlling land subsidence. In this paper, the time-series interferometric data, in situ monitoring data of recent 20 years and the basic geological datasets are combined to compare and analyze the changes of groundwater level, land subsidence and the main subsidence layers along the Beijing-Tianjin high-speed railway before and after the SNWDP-CR. The effects of the environment of Quaternary sedimentary, groundwater exploitation and soil deformation of different lithology on land subsidence along the high-speed railway under the background of new water conditions are revealed. The main conclusions are as follows: 1) The serious land subsidence area along the Beijing-Tianjin high-speed railway always concentrated in the section of DK11-DK23. After the operation of SNWDP-CR, the land subsidence along the railway generally showed a slowing trend. The maximum subsidence rate was reduced from 80 mm/yr to 49 mm/yr. The length of subsidence rate that more than 50 mm/yr of the section was reduced from 8.0 km to 0 km. 2) The groundwater level of different aquifer groups along the Beijing-Tianjin high-speed railway rose and declined before and after the SNWDP-CR. in eastern part of the plain, the groundwater level of each aquifer group has changed from a continuous decline (range 0.13–1.82 m) to a gradual rise (range 0.45–1.87 m) since 2017. However, in the southeast of the plain, the groundwater level still showed a continuous decline trend, with an average annual decline of 1.2–1.8 m. 3) From 2006 to 2019, the subsidence of the first, second and third compression layer group along the railway accounted for 2.71%, 28.29% and 69%, respectively. The third compression layer group (monitoring layer 94–182 m) had the largest subsidence proportion and was the main subsidence layer. 4) The land subsidence along the Beijing-Tianjin high-speed railway is controlled by the basement structure. The difference of groundwater exploitation intensity led to differences in the spatial distribution of land subsidence along the railway. The subsidence of the soil layer below the bearing layer (about 50 m) of the high-speed railway pile foundation exhibited the characteristics of viscoplastic or viscoelastic plasticity deformation. This section of strata is a key layer that needs to be considered for land subsidence control along the Beijing-Tianjin high-speed railway in the future.

In this study, the effects of different enzymes (lysozyme, α-amylase and neutral protease) on sludge hydrolysis efficiency and microbial community in sequencing batch reactor (SBR) were introduced. The results showed that the hydrolysis efficiencies of the three enzymes were 48.5, 22.5 and 31%, respectively, compared with the accumulated sludge discharge of the blank control group. However, it has varying degrees of impact on the effluent quality, and the denitrification and phosphorus removal effect of the system deteriorates. The lysozyme that achieves the optimal sludge hydrolysis effect of 48.5% has the greatest impact on the chemical oxygen demand (COD), total nitrogen (TN), and nitrate nitrogen (NO3−-N) of the effluent. The sludge samples of the control group and the groups supplemented with different enzyme preparations were subjected to high-throughput sequencing. It was found that the number of OTUs (Operational Taxonomic Units) of the samples was lysozyme > α-amylase > blank control > neutral protease. Moreover, the abundance grade curve of the sludge samples supplemented with lysozyme and α-amylase was smoother, and the community richness and diversity were improved by lysozyme and α-amylase. The species diversity of the sludge supplemented with lysozyme and neutral protease was great, and the community succession was obvious. The introduction of enzymes did not change the main microbial communities of the sludge, which were mainly Proteobacteria, Actinobacteria and Bacteroidetes. The effects of three enzyme preparations on sludge reduction and microbial diversity during pilot operation were analyzed, the gap in microbial research was filled, which provided theoretical value for the practical operation of enzymatic sludge reduction.