Meningeal lymphatic vessels (mLVs), the functional lymphatic system present in the meninges, are the key drainage route responsible for the clearance of molecules, immune cells, and cellular debris from the cerebrospinal fluid and interstitial fluid into deep cervical lymph nodes. Aging and ApoE4, the two most important risk factors for Alzheimer’s disease (AD), induce mLV dysfunction, decrease cerebrospinal fluid influx and outflux, and exacerbate amyloid pathology and cognitive dysfunction. Dysfunction of mLVs results in the deposition of metabolic products, accelerates neuroinflammation, and promotes the release of pro-inflammatory cytokines in the brain. Thus, mLVs represent a novel therapeutic target for treating neurodegenerative and neuroinflammatory diseases. This review aims to summarize the structure and function of mLVs and to discuss the potential effect of aging and ApoE4 on mLV dysfunction, as well as their roles in the pathogenesis of AD.

Objective: To describe the clinical manifestations and outcomes of COVID-19, and explore the risk factors of deterioration and death of the disease. Methods: In this retrospective study, we collected data from 121 COVID-19 cases confirmed by RT-PCR and next-generation sequencing in Renmin Hospital of Wuhan University from January 30, 2019, to March 23, 2020, and conducted statistical analysis. Results: A total of 121 patients were included in our study, the median age was 65 years (IQR, 55.0–71.5 years), and 54.5% cases were men. Among those cases, 52 (43.0%) cases progressed to severe, and 14 (11.6%) died. Overall, the most common manifestations were fever (78.5%) and respiratory symptoms (77.7%), while neurological symptoms were found in only 9.9% of the patients. 70.2% of all the cases had comorbidities, including hypertension (40.5%) and diabetes (20.7%). On admission, cases usually show elevated levels of neutrophils (27.3%), D-dimer (72.6%), Interleukin-6 (35.2%), Interleukin-10 (64.4%), high-sensitivity C-reactive protein (82.6%), and lactate dehydrogenase (62.0%), and decreased levels of lymphocytes (66.9%), CD3 cells (67.2%), and CD4 cells (63.0%). The proportional hazard Cox models showed that the risk factors for severity progression and death included comorbidities (HR: 4.53, 95% CI: 1.78–11.55 and HR: 7.81, 95% CI: 1.02–59.86), leukocytosis (HR: 1.13; 95% CI: 1.05–1.22 and HR: 1.25, 95% CI: 1.10–1.42), neutrophilia (HR: 1.15, 95% CI: 1.07–1.13 and HR: 1.28, 95% CI: 1.13–1.46, and elevated LDH (HR: 1.14, 95% CI: 1.12–1.15 and HR: 1.11, 95% CI: 1.10–1.12). Elevated D-dimer (HR: 1.02, 95% CI: 1.01–1.03), IL-6 (HR: 1.01, 95% CI: 1.00–1.02) and IL-10 levels (HR: 1.04, 95% CI: 1.01–1.07) were also risk factors for the progression of disease severity. Meanwhile, lymphopenia and wake immune responses [e.g., lower CD3, CD4, or CD19 counts (all HR < 1)] were associated with disease deterioration and death. Conclusions: Severe cases and death of COVID-19 are associated with older age, comorbidities, organ dysfunction, lymphopenia, high cytokines, and weak immune responses.

Netrin-1 reduction activates AEP that cleaves UNC5C receptor, contributing to AD pathogenesis.

Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.