The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2.

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Correlation between the triglyceride-glucose index and arterial stiffness in Japanese individuals with normoglycaemia: a cross-sectional study.

BACKGROUND: The association between the triglyceride-glucose (TyG) index and arterial stiffness in individuals with normoglycaemia remains unclear. We aimed to evaluate the relationship between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia, providing additional evidence for predicting early arterial stiffness. METHODS: This study included 15,453 adults who participated in the NAGALA Physical Examination Project of the Murakami Memorial Hospital in Gifu, Japan, from 2004 to 2015. Data on clinical demographic characteristics and serum biomarker levels were collected. The TyG index was calculated from the logarithmic transformation of fasting triglycerides multiplied by fasting glucose, and arterial stiffness was measured using the estimated pulse wave velocity calculated based on age and mean blood pressure. The association between the TyG index and arterial stiffness was analysed using a logistic regression model. RESULTS: The prevalence of arterial stiffness was 3.2% (500/15,453). After adjusting for all covariates, the TyG index was positively associated with arterial stiffness as a continuous variable (adjusted odds ratio (OR) = 1.86; 95% Confidence Interval = 1.45-2.39; P<0.001). Using the quartile as the cutoff point, a regression analysis was performed for arterial stiffness when the TyG index was converted into a categorical variable. After adjusting for all covariates, the OR showed an upward trend; the trend test was P<0.001. Subgroup analysis revealed a positive association between the TyG index and arterial stiffness in Japanese individuals with normoglycaemia and different characteristics. CONCLUSION: The TyG index in Japanese individuals with normoglycaemia is significantly correlated with arterial stiffness, and the TyG index may be a predictor of early arterial stiffness.

A Protective Role of Canonical Wnt/ß-Catenin Pathway in Pathogenic Bacteria-Induced Inflammatory Responses.

Inflammation is a complex host defensive response against various disease-associated pathogens. A baseline extent of inflammation is supposed to be tightly associated with a sequence of immune-modulated processes, resulting in the protection of the host organism against pathogen invasion; however, as a matter of fact is that an uncontrolled inflammatory cascade is the main factor responsible for the host damage, accordingly suggesting a significant and indispensable involvement of negative feedback mechanism in modulation of inflammation. Evidence accumulated so far has supported a repressive effect of the canonical Wnt/ß-catenin pathway on microbial-triggered inflammation via diverse mechanisms, although that consequence is dependent on the cellular context, types of stimuli, and cytokine environment. It is of particular interest and importance to comprehend the precise way in which the Wnt/ß-catenin pathway is activated, due to its essential anti-inflammatory properties. It is assumed that an inflammatory milieu is necessary for initiating and activating this signaling, implying that Wnt activity is responsible for shielding tissues from overwhelming inflammation, thus sustaining a balanced physiological condition against bacterial infection. This review gathers the recent efforts to elucidate the mechanistic details through how Wnt/ß-catenin signaling modulates anti-inflammatory responses in response to bacterial infection and its interactions with other inflammatory signals, which warrants further study for the development of specific interventions for the treatment of inflammatory diseases. Further clinical trials from different disease settings are required.

Molecularly imprinted electrochemiluminescence sensor based on a novel luminol derivative for detection of human serum albumin via click reaction.

A novel luminol derivative of N-(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-5-yl)acrylamide (DTA) with excellent luminescence efficiency was designed and synthesized. Furthermore, a molecularly imprinted electrochemiluminescence sensor (MIECLS) was fabricated to detect ultratrace levels of human serum albumin (HSA) with high sensitivity and selectivity via a click reaction. The molecularly imprinted polymers (MIPs) were formed on the electrode surface via electropolymerization with HSA as a template molecule and catechol as a monomer. In the detection process, the -SH group of HSA on the electrode and the C = C bond of acryloyl group in DTA formed a new C-S bond via the Michael addition reaction to construct the MIECLS. The higher the concentration of HSA, the greater electrochemiluminescence (ECL) intensity measured. Taking advantage of MIECLS for ECL detection (scanning potential, - 0.4 to 0.5 V), there was a good linear relationship between ECL intensity and the logarithm of HSA concentration in the range 5 × 10-9 to 1 × 10-13 mg mL-1. The limit of detection (LOD) of the sensor was 1.05 × 10-15 mg mL-1. The sensor exhibited outstanding selectivity and stability. The sensor was applied to detect HSA in human serum with good recoveries of 97.7-105.2%. The concentration of HSA was detected by electrochemical method using the gating effect of MIP.

The higher the household income, the lower the possibility of depression and anxiety disorder: evidence from a bidirectional Mendelian randomization study.

Objectives: Observational studies have demonstrated that household income is associated with morbidity of mental disorders. However, a causal relationship between the two factors remains unclear. Therefore, we investigated the causal relationship between household income status and genetic liability of mental disorders using a bidirectional Mendelian randomization (MR) study. Methods: This MR study included a large cohort of the European population from publicly available genome-wide association study datasets. A random-effects inverse-variance weighting model was used as the main standard, with MR-Egger regression, weighted median, and maximum likelihood estimations performed concurrently as supplements. Sensitivity analysis, consisting of heterogeneity and horizontal pleiotropy tests, was performed using Cochran's Q test, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of the conclusions. Results: A higher household income tended to be associated with a lower risk of genetic liability for depression (odds ratio [OR]: 0.655, 95% confidence interval [CI] = 0.522-0.822, p < 0.001) and anxiety disorder (OR: 0.666, 95% CI = 0.526-0.843, p < 0.001). No associations were observed for schizophrenia (OR: 0.678, 95% CI = 0.460-1.000, p = 0.05), panic disorder (OR: 0.837, 95% CI = 0.445-1.577, p = 0.583), insomnia (OR: 1.051, 95% CI = 0.556-1.986, p = 0.877), obsessive-compulsive disorder (OR: 1.421, 95% CI = 0.778-2.596, p = 0.252), and bipolar disorder (OR: 1.126, 95% CI = 0.757-1.677, p = 0.556). A reverse MR study showed no reverse causal relationship between psychiatric disorders and household income. Sensitivity analysis verified the reliability of the results. Conclusion: Our results revealed that the population with a higher household income tended to have a minor risk of genetic liability in depression and anxiety disorders.

MCNN-DIC: a mechanical constraints-based digital image correlation by a neural network approach.

Digital image correlation (DIC) is a widely used photomechanical method for measuring surface deformation of materials. Practical engineering applications of DIC often encounter challenges such as discontinuous deformation fields, noise interference, and difficulties in measuring boundary deformations. To address these challenges, a new, to the best of our knowledge, DIC method called MCNN-DIC is proposed in this study by incorporating mechanical constraints using neural network technology. The proposed method applied compatibility equation constraints to the measured deformation field through a semi-supervised learning approach, thus making it more physical. The effectiveness of the proposed MCNN-DIC method was demonstrated through simulated experiments and real deformation fields of nuclear graphite material. The results show that the MCNN-DIC method achieves higher accuracy in measuring non-uniform deformation fields than a traditional mechanical constraints-based DIC and can rapidly measure deformation fields without requiring extensive pre-training of the neural network.

A molecularly imprinted sensor for single-molecule detection of pesticide metabolite at the amol/L level sensitized by water-soluble luminol derivative encapsulated liposome via click reaction.

A novel luminol derivative, 4-[(1,4-dioxo-1,2,3,4-tetrahydrophthalazin-5-yl)amino]-4-oxobut-2-enoic acid (ALD) with electrochemiluminescence intensity and stability characteristics similar to luminol, but higher solubility in near neutral solution, was designed and synthesized in this study. Using this derivative, a molecular imprinted electrochemiluminescence sensor (MIECLS) was prepared for the sensitive and selective determination of 2-amino-5-mercapto-1,3,4-thiadiazole (AMT), a metabolite of bismerthiazol, thiediazole copper, thiazole zinc, and other pesticides. The ALD probes encapsulated in liposomes are immobilized on the molecularly imprinted film by light-triggered click reaction, and the concurrent release of multiple probes allows for highly sensitive detection. In the AMT concentration range of 1.00 × 10-18 - 5.00 × 10-13 mol/L, the relation between ECL response and log AMT concentration is linear. With a detection limit of 5.25 × 10-19 mol/L (about 4 - 6 molecules in 10 µL of the sample), the sensor allows for high sensitivity analysis of ultra-trace amounts of small organic compounds. In general, the ECL-based single-molecule detection technique proposed herein might be a promising alternative to fluorescence single-molecule detection.

Peptide YY inhibits transcription and replication of hepatitis B virus by suppressing promoter/enhancer activity.

Hepatitis B virus (HBV) infection is a noteworthy cause of liver diseases, especially cirrhosis and hepatocellular carcinomas. However, the interaction between the host and HBV has not been fully elucidated. Peptide YY (PYY) is a 36-amino-acid gastrointestinal hormone that is mainly involved in the regulation of the human digestive system. This study found that PYY expression was reduced in HBV-expressing hepatocytes and HBV patients. Overexpression of PYY could significantly inhibit HBV RNA, DNA levels, and the secretion of HBsAg. In addition, PYY inhibits HBV RNA dependent on transcription through reducing the activities of CP/Enh I/II, SP1 and SP2. Meanwhile, PYY blocks HBV replication independent on core, polymerase protein and ε structure of pregenomic RNA. These results suggest that PYY can impair HBV replication by suppressing viral promoters/enhancers in hepatocytes. Our data shed light on a novel role for PYY as anti-HBV restriction factor.

Magnetic MXene-based molecularly imprinted electrochemical sensor for methylmalonic acid.

A novel magnetic Ti3C2Tx-MXene/Fe3O4 composite was prepared from Ti3C2Tx and magnetic Fe3O4. The characterizations by electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) exhibited that the Ti3C2Tx/Fe3O4 nanomaterial presented an outstanding conductivity and a large specific area, which could improve the electron transfer rate, leading to the amplification of the sensor's signal. Furthermore, an ultrasensitive molecularly imprinted electrochemical sensor based on MXene/Fe3O4 composites was fabricated for detecting methylmalonic acid (MMA) with high selectivity. The current intensity of differential pulse voltammetry of the sensor presented a good linear relationship with the logarithm of MMA concentration ranging from 9 × 10-15 mol L-1 to 9 × 10-13 mol L-1. The detection limit of the sensor was 2.33 × 10-16 mol L-1. The fabricated sensor was utilized for detecting MMA in human serum samples with excellent recoveries. Therefore, this method significantly improved the sensitivity of detection, and constitutes an  affordable sensing platform for trace detection of organic carboxylic acid.

Association of adiposity indices with prehypertension among Chinese adults: A cross-sectional study.

The association of adiposity indices with prehypertension remains unclear in the Chinese non-hypertensive population. This study aimed to compare the association of adiposity indices, including waist circumference (WC), waist-to-height ratio, body roundness index (BRI), a body shape index (ABSI), and conicity index (CI), and prehypertension in the Chinese population. We recruited 61 475 participants from a population-based screening project in Guangdong province, China. Multiple logistic regression analyses were performed to detect the association between the six adiposity indices and prehypertension. Receiver operator characteristic curve (ROC) analysis was used to evaluate the predictive values of adiposity indices to prehypertension. The individuals were divided into two categories by blood pressure (BP) levels: normotension (<120/80 mmHg) and prehypertension (120-139/80-89 mmHg). A total of 33 233 people had prehypertension, with a prevalence of 54.04% and 42% males. Both logistics regression models presented a positive association between each adiposity index and prehypertension (p < .05), except for ABSI. The body mass index (BMI) was slightly more correlated with prehypertension than any other index. The standardized ORs for the six indices were 1.392, 1.361, 1.406, 1.039, 1.372, and 1.151, respectively. Compared to other adiposity indices, the WC had a significantly higher area under the curve (AUC) for predicting prehypertension (AUC: .619, sensitivity: 57%, specificity: 60.6%). In conclusion, WC and BMI might be the best indicators for prehypertension. Increasing evidence supports avoiding obesity as a preferred primary prevention strategy for prehypertension while controlling other major hypertension risk factors.

Isolation of Cytochrome C for Proteomics with Lindqvist-type Polyiodate Modified Metal Organic Framework.

Separation and purification of Cytochrome C (Cyt-C) is important for proteomic. High efficient and selective pretreatment method for Cyt-C in real samples are always needed. Herein, polyniobate (K7H[Nb6O19]·13H2O, Nb6O19) is modified on a metal-organic framework MIL-125(Ti) through intermolecular hydrogen bonds and an aqueous-stable composite Nb6O19/MIL-125(Ti) is successfully prepared to pretreat complex protein sample. Protein adsorption studies have shown that Nb6O19/MIL-125(Ti) can promote the selective adsorption of Cyt-C due to the synergistic effect of electrostatic and hydrogen-bond interactions. At pH=10.0 (Britton-Robinson buffer), the adsorption efficiency of 300 µL 100 µg·mL-1 Cyt-C onto 1.0 mg Nb6O19/MIL-125(Ti) can reach 99.5%. The adsorption behavior of Cyt-C fits well with the Langmuir adsorption model, corresponding to a maximum theoretical adsorption capacity of 168.35 mg·g-1. Using 3 mol·L-1 NaCl as the eluent, a high elution efficiency of 92.19% is obtained. In addition, the results of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis confirm that Nb6O19/MIL-125(Ti) efficiently adsorbed Cyt-C from scrofa heart extraction. LC-MS/MS spectrometry results show that the purification of Cyt-C reduces the abundance from the 12th to the 154th place after Nb6O19/MIL-125(Ti) treatment. Moreover, low abundant proteins, e.g., Superoxide dismutase 1, IF rod domain-containing protein and Ubiquitin-60S ribosomal protein L40 were considerably enriched. These outcomes confirm the practicability of Nb6O19/MIL-125 (Ti) as a Cyt-C extractant has potential application value in scrofa heart proteomics.

Effect of Temperature on the Physical Salt Attack of Cement Mortars under Repeated Partial Immersion in Sodium Sulfate Solution.

Physical salt attack (PSA) is one of the dominant durability issues of cement-based materials, where salt crystallization pressure is the driving force inducing damage. However, research on the temperature-related deterioration behavior of cement-based materials is limited. In this study, salt-contaminated cement mortars were rewetted at different temperatures. The assessment criteria were based on the visual appearance, weight evolution and size distribution of scaled materials, and the alterations in the microstructure were investigated by microscopy, thermal and mineralogical analyses. The results indicated that more severe damage developed at 5 °C than that at 20 °C due to the greater crystallization pressure caused by the conversion from thenardite (Na2SO4) to mirabilite (Na2SO4·10H2O) at the lower temperature. No damage was observed at 35 °C, since the repeated dissolution and re-crystallization of thenardite were harmless for the specimens. In addition, two distinct damage patterns were observed for PSA performed at 5 °C and 20 °C, namely, granular disintegration and contour scaling.

Interferon-alpha responsible EPN3 regulates hepatitis B virus replication.

Hepatitis B virus (HBV) infection remains a major health problem worldwide, and the current antiviral therapy, including nucleoside analogs, cannot achieve life-long cure, and clarification of antiviral host immunity is necessary for eradication. Here, we found that a clathrin-binding membrane protein epsin3 (EPN3) negatively regulates the expression of HBV RNA. EPN3 expression was induced by transfection of an HBV replicon plasmid, and reduced HBV-RNA level in hepatic cell lines and murine livers hydrodynamically injected with the HBV replicon plasmid. Viral RNA reduction by EPN3 was dependent on transcription, and independent from epsilon structure of viral RNA. Viral RNA reduction by overexpression of p53 or IFN-α treatment, was attenuated by knockdown of EPN3, suggesting its role downstream of IFN-α and p53. Taken together, this study demonstrates the anti-HBV role of EPN3. The mechanism how it decreases HBV transcription is discussed.

Inversion Method of the Young's Modulus Field and Poisson's Ratio Field for Rock and Its Test Application.

As one typical heterogeneous material, the heterogeneity of rock micro parameters has an important effect on its macro mechanical behavior. The study of the heterogeneity of micro parameters is more important to reveal the root cause of deformation and failure. However, as a typical heterogeneous material, the current testing and inversion method is not suitable for micro parameters measurement for the rock. Aiming at obtaining the distribution of micro Young's modulus and micro Poisson's ratio of the rock, based on the digital image correlation method (DIC) and finite element method (FEM), this paper proposed a parameter field inversion method, namely the DF-PF inversion method. Its inversion accuracy is verified using numerical simulation and laboratory uniaxial compression test. Considering the influences of heterogeneity, stress state and dimension difference, the average inversion error of Young's modulus field and Poisson's ratio field are below 10%, and the proportion of elements with an error of less than 15% accounts for more than 86% in the whole specimen model. Compared with the conventional measuring method, the error of macro Young's modulus and macro Poisson's ratio calculated by the DF-PF inversion method is less than 2.8% and 9.07%, respectively. Based on the statistical analysis of Young's modulus field and Poisson's ratio field, the parameter homogeneity and quantitative function relation between the micro parameter and the principal strain can also be obtained in laboratory tests. The DF-PF inversion method provides a new effective method of testing Young's modulus field and Poisson's ratio field of the rocks under complex stress states.

Electrochemical sensor based on Ti3C2 membrane doped with UIO-66-NH2 for dopamine.

A Ti3C2 membrane was prepared by doping UIO-66-NH2 with Ti3C2 through hydrogen bonds. When the doping mass ratio of Ti3C2 and UIO-66-NH2 was 6:1, the electrochemical performance was optimal. Characterization was done by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and electrochemical impedance spectroscopy (EIS) which exhibited hierarchical cave-like physiognomy, large specific area, outstanding electronic conductive network, and excellent film-forming property. Moreover, the Ti3C2 film was analyzed via atomic force microscopy (AFM), which displayed good mechanical properties and rough surface morphology. The fabricated Ti3C2 membrane/GCE sensor was applied to the detection of dopamine (working potential of + 0.264 V vs. Ag/AgCl) with LOD of 0.81 fM and a sensitivity of 14.72 µA fM-1 cm-2. It was demonstrated that the Ti3C2 membrane can be used to construct nonenzymatic sensors with excellent performance. The fabricated sensor has high selectivity and stability and has good practicability with recoveries of 101.2-103.5% and a relative standard deviation (RSD) of 1.2-2.4%.

PM2.5 deregulated microRNA and inflammatory microenvironment in lung injury.

PM2.5 negatively affects human health, particularly lung injury. However, the role of PM2.5-regulated miRNAs in lung injury remains unknown. MiRNA array results showed mmu-miR-467c-5p regulated Prdx6 expression to adapt to lung injury condition, and deregulated miRNAs regulated macrophages to build a localized inflammatory microenvironment. In addition, miRNAs were transferred into adjacent alveolar epithelial cells, regulating the expressions of cell injury signaling pathway-targeted genes, and accelerating local lung tissue injury. NO and RAGE were increased in the coculture supernatant, and SPD was decreased. PM2.5 exposure induced local lung injury, promoted inflammation in local lung tissues, increased capillary permeability in the lung tissue, and rearranged the local lung tissue structure. We also confirmed in AECOPD patients TNF-α and IL-1ß levels are obviously higher than healthy person. These findings provide new mechanistic insights regarding PM2.5 and targeted miRNAs in the inflammatory microenvironment, which increases our knowledge of PM2.5-lung injury interactions.

Imidazole Compounds: Synthesis, Characterization and Application in Optical Analysis.

Imidazole is a five-membered heterocyclic ring containing three carbon atoms, two nitrogen atoms, and two double bonds. Among two nitrogen atoms, one of which carries with a hydrogen atom is a pyrrole-type nitrogen atom, another is a pyridine type nitrogen atom. Hence, the imidazole ring belongs to the π electron-rich aromatic ring and can accept strong suction to the electronic group. Moreover, the nitrogen atom of the imidazole ring is coordinated with metal ions to form metal-organic frameworks. In recent years, because of imidazole compounds' unique optical properties, their applications have attracted more and more attention in optical analysis. Thus, this review has summarized the synthesis, characterization, and application with emphasis on the research progress of imidazole compounds in optical analysis, including fluorescence probe, colorimetric probe, electrochemiluminescence sensor, fiber optical sensor, surface plasmon resonance, etc. This paper will suggest the direction for the development of imidazole-containing sensors with high sensitivity and selectivity.

Liposomes: Preparation, Characteristics, and Application Strategies in Analytical Chemistry.

In recent years, the application of liposomes in the field of analytical chemistry has attracted more and more attention. In this paper, the preparation and characterization of liposomes are briefly summarized, and the research and application of liposomes in organic and biological substances analysis are mainly reviewed, including immobilized liposome chromatography, liposome capillary electrophoresis, liposome application in electrochemical analysis, and optical analysis. The future developments of liposomes in the assay are also prospected.

Highly oxygenated ent-atisane and podocarpane diterpenoids from Excoecaria agallocha.

A new highly oxygenated ent-atisane diterpenoid, namely excagallonoid A (1), together with five known analogues (2 - 6) were isolated from the leaves and twigs of Excoecaria agallocha. Their structures were elucidated on the basis of extensive spectroscopic analyses (HRESIMS, UV, IR, 1 D and 2 D NMR), and the absolute configurations of 1 and 5 were determined by single-crystal X-ray diffraction. Compound 1 represents the first example of an ent-atisane diterpenoid featuring a vicinal 2,3-diol moiety. Compounds 1 and 4 exhibited weak cytotoxicities in vitro against RKO colon cancer cells with IC50 values of 28.7 ± 1.98 and 32.6 ± 2.81 µM, respectively.

Construction of immune/Creutzfeldt-Jakob disease-related gene coexpression network to predict biomarkers.

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy characterized by rapid onset and high mortality. Despite considerable progress in the treatment and diagnosis of CJD, patient prognosis remains poor. Many studies have found that the immune response is associated with the pathophysiology of CJD. However, few studies have reported coexpression correlations between genes associated with CJD and the immune response. This study was undertaken to construct a network of coexpressed immune- and CJD-related genes that may reveal new biomarkers and therapeutic targets for CJD. METHODS: Gene expression data from 11 CJD patients and 10 nonneurological controls were obtained from the Gene Expression Omnibus database. High-confidence protein-protein interaction (PPI) data were downloaded from the Human Protein Reference Database, and gene expression data of immune- and CJD-associated genes were downloaded from the AmiGo16 and DisGeNET databases, respectively. An immune/CJD-related expression network was constructed based on Pearson correlation coefficients and PPI networks, and a CJD-directed neighbour coexpression network was extracted, in which we compared the gene expression patterns and correlations between different groups. The samples were classified using CJD-specific modules, and differentially expressed genes (DEGs) between the CJD and nonneurological controls groups were identified within the CJD-specific modules. Further functional analysis was performed using Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis of genes in each CJD-specific module. RESULTS: We constructed an immune/CJD-related coexpression gene network comprising 2007 nodes and 5268 edges, with immune-associated genes occupying important positions in the network. In the CJD-directed neighbour coexpression network, immune-associated genes exhibited the highest coexpression level with their interacting genes. Results from Pearson correlation analysis showed that most of the CJD-associated genes were positively correlated with immune-associated genes. Screening for CJD-specific modules identified MAPK1, CASP3, APP, MAPT, SNCA, and YWHAH, indicating a close connection between CJD and the immune response. Analyses of coexpression status and expression level of CJD-specific genes revealed a very high coexpression pattern for any two genes, with most genes being DEGs. Finally, KEGG enrichment analyses of all CJD-specific genes showed that the pathophysiology of CJD is closely related to infection and the immune response. CONCLUSIONS: Our coexpression network analysis revealed a close connection between CJD- and immune-associated genes, and we identified six CJD-specific modules. Biological function analysis of CJD-specific module genes revealed that immune responses are associated with CJD pathophysiology and may provide novel diagnostic and therapeutic biomarkers for this disease.