MCP-1 levels in astrocyte-derived exosomes are changed in preclinical stage of Alzheimer's disease

BackgroundAlzheimer's disease (AD) is the most common form of dementia in older adults. There is accumulating evidence that inflammatory processes play a critical role in AD pathogenesis. In this study, we investigated whether inflammatory factors in plasma and astrocyte-derived exosomes (ADEs) from plasma are differentially expressed in the early stages of AD and their potential role in pathological processes in the AD continuum.MethodWe included 39 normal controls (NCs), 43 participants with subjective cognitive decline (SCD), and 43 participants with amnestic mild cognitive impairment (aMCI)/AD. IL-6, IL-8, and MCP-1 in plasma and ADEs from plasma were evaluated using a commercial multiplex Luminex-based kit.ResultsPairwise comparisons between the groups showed no significant differences in plasma levels of IL-6, IL-8, or MCP-1. However, ADEs in the SCD group showed an increase in MCP-1 levels compared to the NC group. To differentiate the preclinical group, discriminant analysis was performed using sex, age, years of education, and genotype. This revealed a difference between the SCD and NC groups (area under the curve: 0.664). A Spearman correlation analysis of MCP-1 in plasma and ADEs showed no or weak correlation in the SCD (R = 0.150, p = 0.350) and aMCI/AD (R = 0.310, p = 0.041) groups, while a positive correlation in the NC group (R = 0.360, p = 0.026).ConclusionPlasma IL-6, IL-8, and MCP-1 levels were not significantly different. However, the concentration of MCP-1 in ADEs is slightly altered during the preclinical phase of AD, which could be a potential role of the central neuron system (CNS) immune response in the AD continuum.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT03370744

Take a Prior from Other Tasks for Severe Blur Removal

Recovering clear structures from severely blurry inputs is a challenging problem due to the large movements between the camera and the scene. Although some works apply segmentation maps on human face images for deblurring, they cannot handle natural scenes because objects and degradation are more complex, and inaccurate segmentation maps lead to a loss of details. For general scene deblurring, the feature space of the blurry image and corresponding sharp image under the high-level vision task is closer, which inspires us to rely on other tasks (e.g. classification) to learn a comprehensive prior in severe blur removal cases. We propose a cross-level feature learning strategy based on knowledge distillation to learn the priors, which include global contexts and sharp local structures for recovering potential details. In addition, we propose a semantic prior embedding layer with multi-level aggregation and semantic attention transformation to integrate the priors effectively. We introduce the proposed priors to various models, including the UNet and other mainstream deblurring baselines, leading to better performance on severe blur removal. Extensive experiments on natural image deblurring benchmarks and real-world images, such as GoPro and RealBlur datasets, demonstrate our method's effectiveness and generalization ability

Serum Procalcitonin Correlates with Renal Function in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure

Background/Aims: To investigate the relationship between elevated serum procalcitonin (PCT) and renal function in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods: HBV-ACLF patients (n = 201) presenting to the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, from January 2013 to November 2016 were categorized into three groups according to serum PCT levels: (i) normal group (n = 74) had PCT of ≤ 0.5 ng/mL; (ii) elevated group (n = 85) had PCT in the range 0.5–1.0 ng/mL; and (iii) highly elevated group (n = 42) had PCT of > 1.0 ng/mL. Thirty-five cases received standard care after admission. Serum PCT levels and renal function were determined during a two-week follow-up. Results: Significant increases in serum creatinine (Cr) were recorded in male and female patients in the elevated group and highly elevated group compared with the normal group (P < 0.05). In addition, serum Cr levels in male and female patients were significantly higher in the highly elevated group than in the elevated group (P < 0.05). The glomerular filtration rate (GFR) was significantly lower in the highly elevated group (P < 0.05) and this group had the highest risk of altered Cr (45.9% in males; 80% in females) and abnormal GFR (37.5%). Serum PCT levels correlated significantly with all renal function parameters including homocysteine (Hcy), GFR, Cr, blood urea nitrogen, uric acid, and cystatin C at baseline and during treatment. Univariate and multivariate analyses indicated that serum PCT was a strong predictor of renal dysfunction. Conclusion: Serum PCT is closely related to renal dysfunction in HBV-ACLF

The Protective Antibodies Induced by a Novel Epitope of Human TNF-α Could Suppress the Development of Collagen-Induced Arthritis

Tumor necrosis factor alpha (TNF-α) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-α (hTNF-α) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-α. We performed screening peptide library against anti-hTNF-α antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-α. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80–91 aa) of hTNF-α proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-α biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-α. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-α and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies

The components of tumor microenvironment as biomarker for immunotherapy in metastatic renal cell carcinoma

Substantial improvement in prognosis among metastatic renal cell carcinoma (mRCC) patients has been achieved, owing to the rapid development and utilization of immunotherapy. In particular, immune checkpoint inhibitors (ICIs) have been considered the backbone of systemic therapy for patients with mRCC alongside multi-targeted tyrosine kinase inhibitors (TKIs) in the latest clinical practice guidelines. However, controversies and challenges in optimal individualized treatment regarding immunotherapy remains still About 2/3 of the patients presented non-response or acquired resistance to ICIs. Besides, immune-related toxicities, namely immune-related adverse events, are still elusive and life-threatening. Thus, reliable biomarkers to predict immunotherapeutic outcomes for mRCC patients are needed urgently. Tumor microenvironment (TME), consisting of immune cells, vasculature, signaling molecules, and extracellular matrix and regulates tumor immune surveillance and immunological evasion through complex interplay, plays a critical role in tumor immune escape and consequently manipulates the efficacy of immunotherapy. Various studied have identified the different TME components are significantly associated with the outcome of mRCC patients receiving immunotherapy, making them potential valuable biomarkers in therapeutic guidance. The present review aims to summarize the latest evidence on the associations between the components of TME including immune cells, cytokines and extracellular matrix, and the therapeutic responses among mRCC patients with ICI-based treatment. We further discuss the feasibility and limitation of these components as biomarkers

Direct transformation of-alkane into all-conjugated polyene via cascade dehydrogenation

Selective C(sp$^{3}$) −H activation is of fundamental importance in processing alkane feedstocks to produce high-value-added chemical products. By virtue of an on-surface synthesis strategy, we report selective cascade dehydrogenation of n-alkane molecules under surface constraints, which yields monodispersed all-trans conjugated polyenes with unprecedented length controllability. We are also able to demonstrate the generality of this concept for alkyl-substituted molecules with programmable lengths and diverse functionalities, and more importantly its promising potential in molecular wiring