Cerebellar and cerebral white matter changes in Parkinson's disease with resting tremor.

PURPOSE: Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). METHODS: In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. RESULTS: In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. CONCLUSION: We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD.

Zinc-α2-glycoprotein relieved seizure-Induced neuronal glucose uptake impairment via insulin-like growth factor 1 receptor-regulated glucose transporter 3 expression.

Glucose hypometabolism is observed in epilepsy and promotes epileptogenesis. Glucose hypometabolism in epilepsy may be attributed to decreased neuronal glucose uptake, but its molecular mechanism remains unclear. Zinc-α2-glycoprotein (ZAG) is related to glucose metabolism and is reported to suppress seizures. The anti-epileptic effect of ZAG may be attributed to its regulation of neuronal glucose metabolism. This study explored the effect of ZAG on neuronal glucose uptake and its molecular mechanism via insulin-like growth factor 1 receptor (IGF1R)-regulated glucose transporter 3 (GLUT-3) expression. The ZAG level was modulated by lentivirus in primary culture neurons. Neuronal seizure models were induced by Mg2+ -free artificial cerebrospinal fluid. We assessed neuronal glucose uptake by the 2-NBDG method and Glucose Uptake Colorimetric Assay Kit. IGF1R was activated by IGF1 and blocked by AXL1717. The expression and distribution of IGF1R and GLUT-3, together with IGF1R phosphorylation, were measured by western blot. The binding between ZAG and IGF1R was determined by coimmunoprecipitation. Neuronal glucose uptake and GLUT-3 expression were significantly decreased by seizure or ZAG knockdown, whereas ZAG over-expression or IGF1 treatment reversed this decrease. The effect of ZAG on neuronal glucose uptake and GLUT-3 expression was blocked by AXL1717. ZAG increased IGF1R distribution and phosphorylation possibly by binding. Additionally, IGF1R increased GLUT-3 activity by increasing GLUT-3 expression. In epilepsy/seizure, neuronal glucose uptake suppression may be attributed to a decrease in ZAG, which suppresses neuronal GLUT-3 expression by regulating the activity of IGF1R. ZAG, IGF1R, and GLUT-3 may be novel potential therapeutic targets of glucose hypometabolism in epilepsy and seizures.

Plasma C-Reactive Protein Level and Outcome of Acute Ischemic Stroke Patients Treated by Intravenous Thrombolysis: A Systematic Review and Meta-Analysis.

INTRODUCTION: The plasma C-reactive protein (CRP) level in predicting prognosis of acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT) is not yet established. This study is aiming to investigate the relationship between the plasma CRP level and outcome of AIS patients receiving IVT. METHODS: PubMed and EMBASE were searched for relevant studies that evaluated the relationship between the CRP level and outcome of AIS patients receiving IVT. STATA 12.0 was used to pool the data for meta-analysis. RESULTS: In total, 8 studies were included. Six studies reported a positive relationship between the high CRP level and unfavorable outcome at 3 months. Five studies associated the high plasma CRP level with high mortality at 3 months. And meta-analysis further confirmed that the high CRP level was related to unfavorable outcomes (odds ratio [OR] = 1.716, 95% CI: 1.170-2.517, p = 0.006) and mortality (OR = 2.751, 95% CI: 1.613-4.693, p < 0.001) at 3 months. However, an elevated CRP level was not found to increase the risk of symptomatic intracerebral hemorrhage. CONCLUSION: A high plasma CRP level was associated with a 3-month poor outcome of AIS patients treated with IVT. CRP may be used as a biomarker for the risk stratification of AIS patients as candidates receiving IVT or other alternative therapy such as mechanical thrombectomy.

Seizure-induced impairment in neuronal ketogenesis: Role of zinc-α2-glycoprotein in mitochondria.

Ketone bodies (KBs) were known to suppress seizure. Untraditionally, neurons were recently reported to utilize fatty acids and produce KBs, but the effect of seizure on neuronal ketogenesis has not been researched. Zinc-α2-glycoprotein (ZAG) was reported to suppress seizure via unclear mechanism. Interestingly, ZAG was involved in fatty acid ß-oxidation and thus may exert anti-epileptic effect by promoting ketogenesis. However, this promotive effect of ZAG on neuronal ketogenesis has not been clarified. In this study, we performed immunoprecipitation and mass spectrometry to identify potential interaction partners with ZAG. The mechanisms of how ZAG translocated into mitochondria were determined by quantitative coimmunoprecipitation after treatment with apoptozole, a heat shock cognate protein 70 (HSC70) inhibitor. ZAG level was modulated by lentivirus in neurons or adeno-associated virus in rat brains. Seizure models were induced by magnesium (Mg2+ )-free artificial cerebrospinal fluid in neurons or intraperitoneal injection of pentylenetetrazole kindling in rats. Ketogenesis was determined by cyclic thio-NADH method in supernatant of neurons or brain homogenate. The effect of peroxisome proliferator-activated receptor γ (PPARγ) on ZAG expression was examined by Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and chromatin immunoprecipitation qRT-PCR. We found that seizure induced ketogenesis deficiency via a ZAG-dependent mechanism. ZAG entered mitochondria through a HSC70-dependent mechanism, promoted ketogenesis by binding to four ß-subunits of long-chain L-3-hydroxyacyl-CoA dehydrogenase (HADHB) and alleviated ketogenesis impairment in a neuronal seizure model and pentylenetetrazole-kindled epileptic rats. Additionally, PPARγ activation up-regulated ZAG expression by binding to promoter region of AZGP1 gene and promoted ketogenesis through a ZAG-dependent mechanism.

Comparative transcriptome analysis of human conjunctiva between normal and conjunctivochalasis persons by RNA sequencing.

Conjunctivochalasis (CCH) is a common ocular disease, especially in aged people. However, the molecular mechanism of CCH on transcriptional level has been unclear. In this study, we characterized the transcriptional landscape of human conjunctiva and compared the transcriptome between normal persons (n = 10) and CCH patients (n = 11). Illumina RNA sequencing (RNA-seq) was performed to obtain transcriptional data, and these data were analyzed using various bioinformatics methods, including read mapping, the analysis of gene expression, gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) metabolic pathway analysis. Additionally, expression patterns of 20 dysregupated genes were validated by qRT-PCR. RNA-seq result showed that clean ratios of 21 samples were more than 95% and more than 92% of all clean reads (32-41 million reads) were mapped to human genome sequence. There were 175 up-regulated genes and 582 down-regulated genes identified in CCH compared to normal persons. Among down-regulated genes in CCH, many genes were related with cell cycle and proliferation, such as BUB1, CCNB1, CCNB2 and CENPA, which might disturb cell growth and proliferation. In addition, several down-regulated genes were associated with keratinization and differentiation of epidermal cells, such as SPRR1A, SPRR1B, and CALML5. In over-expressed genes, CALML6 might play important roles on the development of CCH. The results of qRT-PCR confirmed the accuracy and credibility of RNA-Seq analysis. This study provided a lot of valuable information about pathogenic mechanism of CCH, which could be used to better study CCH in the future.

Statin, cholesterol, and sICH after acute ischemic stroke: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Conflicts exist regarding relationship between prior/new statin use, cholesterol, and early poststroke intracranial hemorrhage (ICH) in acute ischemic stroke (AIS) patients. This meta-analysis is aimed at evaluating the safety of prior/new statin use, cholesterol level and risk of ICH in AIS patients. METHODS: We searched PubMed and Embase for studies examining relation between statin use, cholesterol level, and early poststroke ICH in AIS. Included studies should report risk of early poststroke symptomatic ICH (sICH) or overall ICH. A random-effects model was used to pool the data. RESULTS: Twenty-five articles involving 26,327 participants were included, among whom 925 had sICH. Prior statin use was not associated with overall ICH (adjusted odds ratio (OR), 1.478; 95% confidence interval (CI), 0.924-2.362; p = 0.103) and sICH in patients who received thrombolysis (adjusted OR, 1.567; 95% CI, 0.994-2.471; p = 0.053) or overall ICH in patients, most of whom had not received recanalization therapy (crude OR, 1.342; 95% CI, 0.872-2.065; p = 0.181). New statin use was associated with decreased sICH after recanalization therapy (crude OR, 0.292; 95% CI, 0.168-0.507; p < 0.001).Cholesterol level was not associated with overall ICH. CONCLUSION: Prior/new statin use and lower cholesterol level are not risk factors for sICH and overall ICH in AIS patients, whether or not the patient has received recanalization therapy. New statin use is likely associated with decreased sICH.

Overexpression of zinc-α2-glycoprotein suppressed seizures and seizure-related neuroflammation in pentylenetetrazol-kindled rats.

BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein reported as an anti-inflammatory adipocytokine. Evidences from clinical and experimental studies revealed that brain inflammation plays important roles in epileptogenesis and seizure. Interestingly, closely relationship between ZAG and many important inflammatory mediators has been proven. Our previous study identified ZAG in neurons and found that ZAG is decreased in epilepsy and interacts with TGFß and ERK. This study aimed to investigate the role of ZAG in seizure and explore its effect on seizure-related neuroinflammation. METHODS: We overexpressed AZGP1 in the hippocampus of rats via adeno-associated virus vector injection and observed their seizure behavior and EEG after pentylenetetrazol (PTZ) kindling. The level of typical inflammation mediators including TNFα, IL-6, TGFß, ERK, and ERK phosphorylation were determined. RESULTS: The overexpression of AZGP1 reduced the seizure severity, prolonged the latency of kindling, and alleviated epileptiform discharges in EEG changes induced by PTZ. Overexpression of AZGP1 also suppressed the expression of TNFα, IL-6, TGFß, and ERK phosphorylaton in PTZ-kindled rats. CONCLUSIONS: ZAG may inhibit TGFß-mediated ERK phosphorylation and inhibit neuroinflammation mediated by TNFα and IL-6, suggesting ZAG may suppress seizure via inhibiting neuroinflammation. ZAG may be a potential and novel therapeutic target for epilepsy.

Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.

The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26 °C for more than 9 d and at 37 °C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures.

Expression of visfatin in the diabetic rat retina.

BACKGROUND: Visfatin has been found in adipose tissue, liver and kidney of healthy and diabetic people, with its expression being increased in the aforementioned tissues in diabetes. Based on the former researches, visfatin may exist in the retina and affect the development of diabetic retinopathy. The expression of visfatin in Sprague-Dawley rats' retina, which may carve a path to study the pathogenesis of diabetic retinopathy, was investigated by this study. METHODS: The mRNA and protein expression of visfatin in Sprague-Dawley rats' retina were detected by the reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Immunohistochemical staining was applied to detect the expression location of visfatin in the rats' retinas. RESULTS: The mRNA and visfatin protein expressions in both normal and streptozocin-induced diabetic rats' retina increased significantly in 2 to 8 weeks of diabetes mellitus (DM). Compared with the normal control groups, the difference was statistically significant (P < 0.05). The histological examination showed that the retinal thickness decreased gradually over the course of DM and the decrease in the outer nuclear layer was the most obvious. At 4 and 8 weeks, the decrease in the retinal thickness was significant (P < 0.01). Visfatin was expressed in the retinal nerve fibre layer, inner plexiform layer and outer plexiform layer, and with the progression of DM, its expression was increased. CONCLUSIONS: Visfatin was expressed in the rats' retinas, mainly in the retinal nerve fibre layer, inner plexiform layer and outer plexiform layer. As the development of DM course, its expression was gradually increased.

Protocadherin 17 acts as a tumour suppressor inducing tumour cell apoptosis and autophagy, and is frequently methylated in gastric and colorectal cancers.

Gastric and colorectal cancers are among the most common cancers worldwide and cause serious cancer mortality. Both epigenetic and genetic disruptions of tumour suppressor genes (TSGs) are frequently involved in their pathogenesis. Here, we studied the epigenetic and genetic alterations of a novel TSG-PCDH17 and its functions in the pathogenesis of these tumours. We found that PCDH17 was frequently silenced and methylated in almost all gastric and colorectal tumour cell lines as well as in ∼95% of primary tumours, but not in normal gastric and colonic mucosa. Moreover, its deletion was detected in only 18% of gastric and 12% of colorectal cancer tissues, suggesting that epigenetic and genetic inactivation of PCDH17 are both involved in gastric and colorectal tumourigenesis. PCDH17 protein expression was significantly correlated with low tumour stage and less lymph node metastasis of gastric and colorectal cancer patients, indicating its potential as a tumour marker. Restoring PCDH17 expression inhibited tumour cell growth in vitro and in vivo through promoting apoptosis, as evidenced by increased TUNEL staining and caspase-3 activation. Furthermore, PCDH17-induced autophagy, along with increased numbers of autophagic vacuoles and up-regulated autophagic proteins Atg-5, Atg-12 and LC3B II. Thus, PCDH17 acts as a tumour suppressor, exerting its anti-proliferative activity through inducing apoptosis and autophagy, and is frequently silenced in gastric and colorectal cancers. PCDH17 methylation is a tumour-specific event that could serve as an epigenetic biomarker for these tumours.

Corpus callosum and cerebellum participate in semantic dysfunction of Parkinson's disease: a diffusion tensor imaging-based cross-sectional study.

Language dysfunction is common in Parkinson's disease (PD) patients, among which, the decline of semantic fluency is usually observed. This study aims to explore the relationship between white matter (WM) alterations and semantic fluency changes in PD patients. 127 PD patients from the Parkinson's Progression Markers Initiative cohort who received diffusion tensor imaging scanning, clinical assessment and semantic fluency test (SFT) were included. Tract-based special statistics, automated fiber quantification, graph-theoretical and network-based analyses were performed to analyze the correlation between WM structural changes, brain network features and semantic fluency in PD patients. Fractional anisotropy of corpus callosum, anterior thalamic radiation, inferior front-occipital fasciculus, and uncinate fasciculus, were positively correlated with SFT scores, while a negative correlation was identified between radial diffusion of the corpus callosum, inferior longitudinal fasciculus, and SFT scores. Automatic fiber quantification identified similar alterations with more details in these WM tracts. Brain network analysis positively correlated SFT scores with nodal efficiency of cerebellar lobule VIII, and nodal local efficiency of cerebellar lobule X. WM integrity and myelin integrity in the corpus callosum and several other language-related WM tracts may influence the semantic function in PD patients. Damage to the cerebellum lobule VIII and lobule X may also be involved in semantic dysfunction in PD patients.

A novel variant of the RON receptor tyrosine kinase derived from colorectal carcinoma cells which lacks tyrosine phosphorylation but induces cell migration.

Generation of splice variants in the RON receptor tyrosine kinase facilitates the invasive phenotype of colorectal cancers. Here, we report a new splice variant of RON in the human colorectal cancer cell line HCT116. This variant is encoded by a transcript differing from the full-length RON mRNA by an in-frame deletion of 106 amino acids in the extracellular domain of RON ß-chain. The deleted transcript originates by an alternative deletion of exon 2 and exon 3. The molecular weight of this variant is 160 kDa. Thus, we named this variant RONΔ160(E2E3). This variant is a single-chain protein and expressed in the intracellular compartment. We found that RONΔ160(E2E3) had no tyrosine phosphorylation ability, but it has constitutively activated Akt activity in transfected HEK293 epithelial cells. The expression of this variant in HEK293 cells resulted in an increased migratory activity in vitro mediated through the PI-3K/Akt pathway. Our data describes a new splice variant of RON and suggests a novel role for the RON receptor in the progression of metastasis in colorectal cancer.

Epileptiform Discharges Reduce Neuronal ATP Production by Inhibiting F0F1-ATP Synthase Activity via A Zinc-α2-Glycoprotein-Dependent Mechanism.

Neuronal energy metabolism dysfunction, especially adenosine triphosphate (ATP) supply decrease, is observed in epilepsy and associated with epileptogenesis and prognosis. Zinc-α2-glycoprotein (ZAG) is known as an important modulator of energy metabolism and involved in neuronal glucose metabolism, fatty acid metabolism, and ketogenesis impairment in seizures, but its effect on neuronal ATP synthesis in seizures and the specific mechanism are unclear. In this study, we verified the localization of ZAG in primary cultured neuronal mitochondria by using double-labeling immunofluorescence, immune electron microscopy, and western blot. ZAG level in neuronal mitochondria was modulated by lentiviruses and detected by western blot. The F0F1-ATP synthase activity, ATP level, and acetyl-CoA level were measured. The binding between ZAG and F0F1-ATP synthase was determined by coimmunoprecipitation. We found that both ZAG and F0F1-ATP synthase existed in neuronal mitochondria, and there was mutual binding between them. Epileptiform discharge-induced decrease of mitochondrial ZAG level was reversed by ZAG overexpression. Epileptiform discharge or ZAG knockdown decreased F0F1-ATP synthase activity and ATP level in neurons, which were reversed by ZAG overexpression, while overexpression of ZAG along only increased F0F1-ATP synthase activity but not increased ATP level. Meanwhile, neither epileptiform discharges nor changes of ZAG level can alter the acetyl-CoA level. Moreover, epileptiform discharge did not alter F0F1-ATP synthase level. In conclusion, epileptiform discharge-induced ZAG decrease in neuronal mitochondria is correlated to F0F1-ATP synthase activity inhibition, which may possibly lead to ATP supply impairments. ZAG may be a potential therapeutic target for treating neuronal energy metabolism dysfunction in seizures with further researches.

Risk factors related to early neurological deterioration in lacunar stroke and its influence on functional outcome.

OBJECTIVE: To identify risk factors for early neurological deterioration (END) in acute lacunar stroke patients and its influence on functional outcome. METHODS: Consecutive acute lacunar stroke patients defined by magnetic resonance imaging (MRI) between January 2018 and June 2020 were included in the study. END was defined as any persisting increase in National Institutes of Health Stroke Scale (NIHSS) score of ⩾ 2 points post admission, and favorable outcome was defined as a modified Rankin Scale (mRS) of 0-2 at discharge. Univariable and multivariable logistic regression were performed to identify risk factors related to END, as well as the influence of END on functional outcome. RESULTS: Among a total of 638 lacunar stroke patients (420 males (65.8%), median age 66 years (interquartile range (IQR): 56-74)), 108 (16.9%) developed END, and 94.4% (102/108) of the END occurred within 72 h post admission. Admission NIHSS score (adjusted odds ratio (aOR) 1.132, 95% confidence interval (CI) 1.046-1.225, p = 0.002), female (aOR 2.752, 95% CI 1.277-5.933, p = 0.010), admission systolic blood pressure (SBP) (160-179 mm Hg) (aOR 9.395, 95% CI 4.310-20.479, p < 0.001) and admission SBP (⩾180 mm Hg) (aOR 16.030, 95% CI 5.991-42.891, p < 0.001) were significantly associated with END. Delay time from onset to admission (aOR 0.995, 95% CI 0.990-1.000, p = 0.031), SBP dropping (⩾20 mm Hg) within 3 days or when END occurred (aOR 0.037, 95% CI 0.016-0.086, p < 0.001) and thalamic lacunar infarction (aOR 0.098, 95% CI 0.012-0.827, p = 0.033) were inversely associated with END. END (aOR 12.374, 95% CI 6.881-22.254, p < 0.001) and higher admission NIHSS score (aOR 1.488, 95% CI 1.359-1.629, p < 0.001) predicted unfavorable outcome at discharge. CONCLUSION: END in lacunar stroke patients is common and is associated with unfavorable outcome. Admission high SBP is a potentially modifiable risk factor for prevention of END, but this needs further investigation.

Collagen changes in rabbit conjunctiva after conjunctival crosslinking.

This study aims to determine the ultrastructural changes in collagen fibrils in rabbit conjunctiva after conjunctival crosslinking using riboflavin and ultraviolet A (UVA) light at an irradiation intensity of 45 mW/cm2. Conjunctival crosslinking may increase conjunctival stiffness. The supertemporal quadrants of the right eyes of 24 adult rabbits were treated with a topical riboflavin solution (0.25%) before irradiation with UVA light at 45 mW/cm2 for 4 min. After 3 weeks, the collagen fibrils in fibril bundles were examined by electron microscopy. Immunohistochemical staining was used to detect the expression levels of collagen I and collagen III in the rabbits' conjunctiva. The diameter of the collagen fibrils in the fibril bundles varied slightly, ranging from 30 to 60 nm in the conjunctival stroma of the control group. In the treatment group, the diameter of collagen fibrils ranged from 60 to 90 nm. The thickest collagen fibrils were observed in the treatment group (up to 90 nm in diameter). In contrast, those in the conjunctival stroma of the control group were considerably smaller (up to 60 nm in diameter). However, thicknesses of collagen fibrils displayed a unimodal distribution. Both collagen I and collagen III increased after treatment with riboflavin and UVA light irradiation at 45 mW/cm2. The data indicate that in rabbits, conjunctival crosslinking with riboflavin and UVA light at 45 mW/cm2 for 4 min is safe and does not induce ultrastructural alterations of the conjunctival cells. The conjunctival crosslinking with riboflavin and UVA light at 45 mW/cm2 can increase the diameter of collagen fibrils, but the average densities of collagen I and collagen III have no statistical significance.

Glucose metabolism impairment in Parkinson's disease.

Impairments in systematic and regional glucose metabolism exist in patients with Parkinson's disease (PD) at every stage of the disease course, and such impairments are associated with the incidence, progression, and special phenotypes of PD, which affect each physiological process of glucose metabolism including glucose uptake, glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and pentose phosphate shunt pathway. These impairments may be attributed to various mechanisms, such as insulin resistance, oxidative stress, abnormal glycated modification, blood-brain-barrier dysfunction, and hyperglycemia-induced damages. These mechanisms could subsequently cause excessive methylglyoxal and reactive oxygen species production, neuroinflammation, abnormal aggregation of protein, mitochondrial dysfunction, and decreased dopamine, and finally result in energy supply insufficiency, neurotransmitter dysregulation, aggregation and phosphorylation of α-synuclein, and dopaminergic neuron loss. This review discusses the glucose metabolism impairment in PD and its pathophysiological mechanisms, and briefly summarized the currently-available therapies targeting glucose metabolism impairment in PD, including glucagon-likepeptide-1 (GLP-1) receptor agonists and dual GLP-1/gastric inhibitory peptide receptor agonists, metformin, and thiazoledinediones.

Eggshell-inspired biomineralization generates vaccines that do not require refrigeration.

We're not gonna bake it: In situ biomineralization creates an egg-like shell on vaccine particles to improve their thermostability. Different from the bare vaccine (squares), the biomineralized vaccine (red circles) can be stored at ambient temperature without refrigeration for up to a week and retain biological activity both in vitro (see graph), as well as in a mouse model.

Characterization of plant growth-promoting traits of Enterobacter sp. and its ability to promote cadmium/lead accumulation in Centella asiatica L.

In the present study, we characterized the plant growth-promoting traits of Enterobacter sp. FM-1 (FM-1) and investigated its ability to promote growth and increase IAA, P, and Fe concentrations as well as Cd and Pb accumulation in Centella asiatica L. (C. asiatica L.) in upstream area (UA) soil and downstream area (DA) soil that we collected from Siding mine. The results demonstrated that FM-1 secreted IAA, produced siderophores, and had P-solubilization ability even under Cd exposure. IAA secretion reached a maximum of 108.3 ± 1.3 mg L-1 under Cd exposure at 25 mg L-1. Siderophore production reached a maximum of 0.94 ± 0.01 under Cd exposure at 50 mg L-1. Pot experiments indicated that FM-1 successfully colonized the roots of C. asiatica L. In both soils, inoculation with FM-1 decreased the pH in rhizosphere soil and increased the bioavailability of both Cd and Pb. In addition, inoculation with FM-1 increased the IAA, P, and Fe concentrations and simultaneously promoted both Cd and Pb accumulation in C. asiatica L. The Cd and Pb concentrations in leaves increased 1.73- and 1.07-fold in the UA soil and 1.25- and 1.11-fold in the DA soil, respectively. Thus, the Cd-resistant strain FM-1 presented excellent PGP traits and could facilitate Cd and Pb phytoremediation by C. asiatica L.

Diffusion-weighted imaging lesions after endovascular treatment of cerebral aneurysms: A network meta-analysis.

Background: Thromboembolism is one of the common complications in endovascular treatments including coiling alone, stent-assisted coiling (SAC), balloon-assisted coiling (BAC), and flow-diverting (FD) stents. Such treatments are widely used in intracranial aneurysms (IAs), which usually present as positive lesions in diffusion-weighted imaging (DWI). Whether these adjunctive techniques increase postprocedural DWI-positive lesions after endovascular treatment remains unclear. Methods: A thorough electronic search for the literature published in English between January 2000 and October 2022 was conducted on PubMed, Medline, and EMBASE. Eighteen studies (3 cohort studies and 15 case-control studies) involving 1,843 patients with unruptured IAs (UIAs) were included. We performed a frequentist framework network meta-analysis (NMA) to compare the rank risks of cerebral thromboembolism of the above four endovascular treatments. The incoherence test was used to analyze the statistical disagreement between direct and indirect evidence. Funnel plots were used to analyze publication bias. Results: The incidences of DWI lesions in patients who received FD stents, SAC, BAC, and coiling alone were 66.1% (109/165), 37.6% (299/795), 31.1% (236/759), and 25.6% (236/921). The incidence of DWI lesions in patients who received FD stents was higher than that in patients who received SAC [OR: 2.40; 95% CI (1.15, 5.00), P < 0.05], BAC [OR: 2.62; 95% CI (1.19, 5.77), P < 0.05], or coiling alone [OR: 2.77; 95% CI (1.26, 6.07), P < 0.05]. The incoherence test showed preferable consistency in this NMA. No obvious publication bias was found in the funnel plot. Conclusion: FD stent placement brings more ischemic lesions identified by DWI than any other procedures for patients with UIA. The characteristics of FD stents may result in a high incidence of DWI lesions.

Effects of Anti-Parkinsonian Drugs on Verbal Fluency in Patients with Parkinson's Disease: A Network Meta-Analysis.

Verbal fluency impairment is common in patients with Parkinson's disease (PD), but the effect of drugs on verbal fluency in PD patients has not been comprehensively evaluated. We conducted a network meta-analysis based on four online databases to compare the effect of drugs on verbal fluency in PD patients. This study was performed and reported according to PRISMA-NMA guidelines. In total, 6 out of 3707 articles (three RCTS and three cross-sectional studies) covering eight drug regimens were included (five for letter fluency, five for semantic fluency). In terms of letter fluency, the ranking of the overall efficacy of included drug regimens was: levodopa, levodopa combined with pramipexole, rotigotine, cabergoline, pramipexole, pergolide, but no drug regimen presented a significant advantage over the others. In terms of semantic fluency, the ranking of the overall efficacy of included drug regimens was: rotigotine, levodopa, cabergoline, pergolide, pramipexole, among which, levodopa alone (SMD = 0.93, 95%CI: 0.28-1.59) and rotigotine alone (SMD = 1.18, 95%CI: 0.28-2.09) were statistically superior to pramipexole, while no significant difference was identified between all the other drug regimens. Levodopa and rotigotine seem to be more appropriate choices for PD patients with verbal fluency impairment. Further study is needed to illustrate the efficacy of drugs on verbal fluency in PD patients.