Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

Laccase is a type of polyphenol oxidase that can catalyze the oxidation of various substances,including phenols,aromatic amines,and catecholamines.It has been widely utilized in pollutant degradation and analytical applications.However,the high cost of preparation of natural laccase and its susceptibility to environmental factors,which can lead to denaturation and inactivation,limit its practical applications.Nanozymes,which are nanomaterials that exhibit enzyme-like properties,offer advantages such as easy preparation,adjustable activity,and exceptional stability.Currently,many types of nanozymes have been developed.Inspired by the coordination of Cu2+with amino acids in the active site of natural laccase,researchers have employed coordination synthetic strategies to prepare laccase-like nanozymes.The metal nodes in these laccase-like nanozymes include copper,manganese,and cerium,while the ligands involve a variety of chemicals like nucleotides,amino acids,polypeptides,and aromatic acids.By manipulating factors such as the metal-to-ligand ratio,reducing capacity of ligands,buffer solutions,chloride ions,bromine ions,the catalytic activity of laccase-like nanozymes can be finely tuned.In this paper,laccase-like nanozymes developed through coordination strategies were categorized and summarized,along with review of their analytical applications in detection of phenolic compounds,disease biomarkers,antibiotics,pesticides,sulfur-containing pollutants,and time-temperature indicators.Furthermore,the challenges currently faced in the research of laccase-like nanozymes and future research directions were discussed.

Creutzfeldt-Jakob disease(CJD)is a rare neurodegenerative disorder characterized by abnor-malities in the prion protein(PrP),the most common form of human prion disease.Although Genome-Wide Association Studies(GWAS)have identified numerous risk genes for CJD,the mechanisms under-lying these risk loci remain poorly understood.This study aims to elucidate novel genetically prioritized candidate proteins associated with CJD in the human brain through an integrative analytical pipeline.Uti-lizing datasets from Protein Quantitative Trait Loci(pQTL)(NpQTL1=152,NpQTL2=376),expres-sion QTL(eQTL)(N=452),and the CJD GWAS(NCJD=4 110,NControls=13 569),we imple-mented a systematic analytical pipeline.This pipeline included Proteome-Wide Association Study(PWAS),Mendelian randomization(MR),Bayesian colocalization,and Transcriptome-Wide Associa-tion Study(TWAS)to identify novel genetically prioritized candidate proteins implicated in CJD patho-genesis within the brain.Through PWAS,we identified that the altered abundance of six brain proteins was significantly associated with CJD.Two genes,STX6 and PDIA4,were established as lead causal genes for CJD,supported by robust evidence(False Discovery Rate＜0.05 in MR analysis;PP4/(PP3+PP4)≥0.75 in Bayesian colocalization).Specifically,elevated levels of STX6 and PDIA4 were asso-ciated with an increased risk of CJD.Additionally,TWAS demonstrated that STX6 and PDIA4 were asso-ciated with CJD at the transcriptional level.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

ObjectiveGlutathione (γ-glutamyl-L-cysteinylglycine, GSH) is the most abundant non-protein compound containing sulfhydryl (―SH) groups in cells. It serves as a source of reducing equivalents, effectively neutralizing harmful reactive substances, and playing a crucial role in maintaining cellular redox balance. Therefore, sensitive detection and accurate measurement of GSH levels in tissues are of great importance. In this work, we presents a novel method for GSH detection utilizing electron paramagnetic resonance (EPR) spectroscopy. MethodsInitially, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate acid)) solution was mixed with K₂S₂O₈ solution and reacted in the dark for 12 to 16 h to prepare ABTS·⁺ solution, which was then quantified using UV-Vis spectroscopy. Subsequently, the concentration of glutathione (GSH) was determined based on the changes in the EPR signal of ABTS·⁺. On this basis, the optimal reaction time and temperature were explored to establish a standard equation correlating the EPR signal intensity of ABTS·⁺ with GSH concentration. Finally, the derived standard curve was employed to quantitatively analyze the GSH concentration in whole blood from C57BL/6J mice, and the results were compared with those reported in the literature to verify the accuracy of the method. ResultsThe experimental results demonstrate that this method has a linear detection range from50 nmol/L to 15 μmol/L for GSH, spanning two orders of magnitude, with a limit of detection (LOD) at0.50 nmol/L. The measured GSH content in mouse whole blood is (10 660±706) nmol/g Hb, which agrees with the value of (11 200±237) nmol/g Hb as previously reported. Furthermore, a similar method was developed for detection of glutathione disulfide (GSSG) at higher reaction temperature. ConclusionThis article presents a novel assay for the rapid detection of GSH using the intensity of EPR signal from ABTS·⁺ as indicator. This method demonstrates enhanced detection sensitivity and a broader linear range compared to conventional colorimetric methods. Furthermore, we have extended the application of this method to detect GSH content in blood samples efficiently and accurately, offering valuable information for assessing tissue redox balance, thus holding significant potentials.

According to the theory of traditional Chinese medicine(TCM),benign prostatic hyperplasia(BPH)belongs to the category of"Jing Long".Clinical management of BPH in TCM is root-aimed and kidney-targeted,in combination with the treatment of other viscera based on the syndrome differentiation of zang-fu organs.The neuro-endocrine-immune network of modern medicine is simi-lar to the holistic concept of TCM.Based on the study of the neuro-endocrine-immune network,with kidney deficiency as the root of pathogenesis,and starting from the classification of viscera,this review elucidates the etiologic mechanisms of BHP from the perspec-tive of Chinese and Western medicine and provides some reference for medication.

AIM: To compare the changes of corneal refractive power before and after wearing defocus rigid gas permeable contact lens(RGPCL)in children with high myopia, and to analyze its influence on corneal refractive power and astigmatism after wearing glasses.METHODS: Self-controlled before-after study. A total of 30 cases(60 eyes)of children aged 8-12, with high myopia who were treated and fitted with defocus RGPCL in the Optometry Center of Xi'an First Hospital from June 2019 to June 2020 were collected. Using TMS-4N corneal topography instrument to measure the corneal tangential refractive power at baseline and wearing lens for 0.5 and 1a, and analyze the nasal side(N), temporal side(T), superior(S)and inferior(I)of the maximum corneal refractive power values at the 4 axial directions and the changes of the corneal refractive power at the center were collected at the same time at 1 mm intervals. The changes of corneal refractive power at each point before and after wearing glasses were analyzed. The axial length, diopter and corneal topography were required to be measured after 0.5 and 1a, and the changes in axial length, spherical equivalent, astigmatism and corneal refraction compared with baseline were analyzed.RESULTS: The maximum corneal refractive power of nasal(N), temporal(T), superior(S)and inferior(I)side was significantly increased at 0.5 and 1a when wearing defocus RGPCL compared with that before wearing glasses, which all showed positive relative refractive power compared with the corneal refractive power at center and was significantly different from the negative relative refractive power before wearing lenses. The relative peripheral refractive power of the cornea changed in the direction of positive refractive power when the lenses were worn for 0.5 and 1a. Except for the increase in the peripheral negative refractive power at the T1 point, the peripheral refractive power at all points in the other axes increased significantly. After wearing for 0.5a, the corneal steep K value became flat by 0.11±0.10D, the simK value decreased by 0.20±0.18D, the corneal steep K value became flat by 0.10±0.12D after 1a, the average K value became flat by 0.02±0.05D, and the simK value decreased by 0.16±0.13D. There was no significant difference in corneal level K from the baseline after wearing glasses for 0.5 and 1a.CONCLUSIONS: The maximum refractive power of the cornea in the state of wearing defocus RGPCL is positive relative refractive power compared with the vertex of cornea, and the relative peripheral negative refractive power of the cornea at each point on the 4 axes changes from negative value to positive value. Within 1a of wearing glasses, the axial length and spherical equivalent increased compared with the baseline, while the amount of astigmatism decreased, and the corneal refractive power showed a trend of steep K and flattening.

Objective: To investigate the relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status. Methods: The demographic data and biochemical indicators of the adult population who had received physical examination in the Second Medical Center of the PLA General Hospital from January 2018 to December 2021 were collected. The subjects were divided into two groups according to the level of serum uric acid: the normal uric acid group and the hyperuricemia group. The relationship between hemoglobin (stratified into four levels of Q₁ to Q₄ by the quartile) and serum uric acid was quantified by using Pearson correlation and logistic regression analysis. The effects of age and glucose metabolism status on the relationship between hemoglobin and serum uric acid were analyzed. Results: A total of 33 183 adults were enrolled with age (50.6±10.0) years. The level of hemoglobin in the normal uric acid group (142.61±14.24) g/L was significantly lower than that in the hyperuricemia group [(151.79±11.24) g/L, P<0.001]. Univariate Pearson correlation analysis showed that hemoglobin was positively associated with serum uric acid (r=0.444, P<0.001). After adjusting for related confounding factors, multivariate logistic regression analysis showed that hemoglobin was associated with serum uric acid, and the OR values (95%CI) of hemoglobin Q₂ to Q₄ group were 1.29 (1.13-1.48), 1.42 (1.24-1.62) and 1.51 (1.32-1.72), respectively (P_trend<0.001) when compared with hemoglobin Q₁ group. Subgroup analysis and hierarchical interaction analysis suggested that with the increase of hemoglobin, the serum uric acid in the age<60 years subgroup, normal glucose subgroup and prediabetes subgroup increased gradually (P_trend<0.05 and P_interaction<0.001). Conclusion: The association between hemoglobin and serum uric acid in adults is affected by age and glucose metabolism status.
Humans ; Adult ; Middle Aged ; Uric Acid ; Hyperuricemia/epidemiology* ; Hemoglobins ; Prediabetic State ; Glucose ; Risk Factors

OBJECTIVE: To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes. METHODS: A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents. RESULTS: The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (P_interaction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis. CONCLUSION Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.
Humans ; Male ; Middle Aged ; Aged ; Female ; Metformin/adverse effects* ; Diabetes Mellitus, Type 2/drug therapy* ; Cohort Studies ; Ischemic Stroke/complications* ; Prospective Studies ; Hypoglycemic Agents/adverse effects* ; Stroke/prevention & control* ; Retrospective Studies