IMPORTANCE While the outbreak of coronavirus disease 2019 has resulted in more than 100 000 infected individuals in China and worldwide, there are few reports on the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular abnormalities. Understanding ocular manifestations of patients with COVID-19 by ophthalmologists and others may facilitate the diagnosis and prevention of transmission of the disease. OBJECTIVE To investigate ocular manifestations and viral prevalence in the conjunctiva of patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS In this case series, patients with COVID-19 treated from February 9 to 15, 2020, at a hospital center in Hubei province, China, were retrospectively reviewed for ocular manifestations. During the period of treatment, the ocular signs and symptoms as well as results of blood tests and reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for SARS-CoV-2 were noted and analyzed.MAIN OUTCOMES AND MEASURES Ocular signs and symptoms as well as results of blood tests and RT-PCR for SARS-CoV-2. RESULTSOf the 38 included patients with clinically confirmed COVID-19, 25 (65.8%) were male, and the mean (SD) age was 65.8 (16.6) years. Among them, 28 patients (73.7%) had positive findings for COVID-19 on RT-PCR from nasopharyngeal swabs, and of these, 2 patients (5.2%) yielded positive findings for SARS-CoV-2 in their conjunctival as well as nasopharyngeal specimens. A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had ocular manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis, epiphora, or increased secretions. By univariate analysis, patients with ocular symptoms were more likely to have higher white blood cell and neutrophil counts and higher levels of procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular symptoms. In addition, 11 of 12 patients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8) had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, 2 (16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and nasopharyngeal swabs. CONCLUSIONS AND RELEVANCEIn this study, one-third of patients with COVID-19 had ocular abnormalities, which frequently occurred in patients with more severe COVID-19. Although there is a low prevalence of SARS-CoV-2 in tears, it is possible to transmit via the eyes.

Physiologically, four major types of hepatic cells - the liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and hepatocytes - reside inside liver sinusoids and interact with flowing peripheral cells under blood flow. It is hard to mimic an in vivo liver sinusoid due to its complex multiple cell-cell interactions, spatiotemporal construction, and mechanical microenvironment. Here we developed an in vitro liver sinusoid chip by integrating the four types of primary murine hepatic cells into two adjacent fluid channels separated by a porous permeable membrane, replicating liver's key structures and configurations. Each type of cells was identified with its respective markers, and the assembled chip presented the liver-specific unique morphology of fenestration. The flow field in the liver chip was quantitatively analyzed by computational fluid dynamics simulations and particle tracking visualization tests. Intriguingly, co-culture and shear flow enhance albumin secretion independently or cooperatively, while shear flow alone enhances HGF production and CYP450 metabolism. Under lipopolysaccharide (LPS) stimulations, the hepatic cell co-culture facilitated neutrophil recruitment in the liver chip. Thus, this 3D-configured in vitro liver chip integrates the two key factors of shear flow and the four types of primary hepatic cells to replicate key structures, hepatic functions, and primary immune responses and provides a new in vitro model to investigate the short-duration hepatic cellular interactions under a microenvironment mimicking the physiology of a liver.

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a b s t r a c tThe maintenance of stem cell pluripotency or stemness is crucial to embryonic development and differentiation. The mechanical or physical microenvironment of stem cells, which includes extracellular matrix stiffness and topography, regulates cell morphology and stemness. Although a growing body of evidence has shown the importance of these factors in stem cell differentiation, the impact of these biophysical or biomechanical regulators remains insufficiently characterized. In the present study, we applied a micro-fabricated polyacrylamide hydrogel substrate with two elasticities and three topographies to systematically test the morphology, proliferation, and stemness of mESCs. The independent or combined impact of the two factors on specific cell functions was analyzed. Cells are able to grow effectively on both polystyrene and polyacrylamide substrates in the absence of feeder cells. Substrate stiffness is predominant in preserving stemness by enhancing Oct-4 and Nanog expression on a soft polyacrylamide substrate. Topography is also a critical factor for manipulating stemness via the formation of a relatively flattened colony on a groove or pillar substrate and a spheroid colony on a hexagonal substrate. Although topography is less effective on soft substrates, it plays a role in retaining cell stemness on stiff, hexagonal or pillar-shaped substrates. mESCs also form, in a timely manner, a 3D structure on groove or hexagonal substrates. These results further the understanding of stem cell morphology and stemness in a microenvironment that mimics physiological conditions.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

Apolipoprotein E (ApoE), encoded by the ApoE gene (APOE), influences the outcomes of traumatic brain injury (TBI), but the mechanism remains unclear. The present study aimed to investigate the effects of different ApoEs on the outcome of TBI and to explore the possible mechanisms. Controlled cortical impact (CCI) was performed on APOEε3 (E3) and APOEε4 (E4) transgenic mice, APOE-KO (KO) mice, and wild type (WT) mice to construct an in vivo TBI model. Neurological deficits, blood brain barrier (BBB) permeability and brain edema were detected at days 1, 3, and 7 after TBI. The results revealed no significant differences among the four groups at day 1 or day 3 after injury, but more severe deficits were found in E4 and KO mice than in E3 and WT mice. Furthermore, a significant loss of tight junction proteins was observed in E4 and KO mice compared with E3 and WT mice at day 7. Additionally, more expression and activation of NF-κB and MMP-9 were found in E4 mice compared with E3 mice. Different ApoEs had distinct effects on neuro-function and BBB integrity after TBI. ApoE3, but not E4, might inhibit the NF-κB/MMP-9 pathway to alleviate BBB disruption and improve TBI outcomes.

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Background & aims Sarcopenia is associated with poor clinical outcomes of patients who underwent esophagectomy. The current diagnostic criteria for sarcopenia are complex and laborious. We aimed to employ the simple and economic indicator sarcopenia index (SI = creatinine/cystatin C ×100) to screen for sarcopenia and to evaluate its prognostic value in patients with esophageal cancer (EC). Methods Older participants in the National health and nutrition examination survey (NHANES) database (1999–2002) were divided into three groups according to tertiles of the SI value to explore the feasibility of SI in the diagnosis of sarcopenia. Restricted cubic spline (RCS) was utilized to show the non-linear relationship between all-cause mortality and SI. Patients with EC admitted to Jinling Hospital were enrolled to validate the efficacy and prognostic value of SI. Cut-off values of SI were determined using receiver operating characteristic curves. Multivariable logistic analyses and Cox analyses were used to identify the independent factors of postoperative complications and long-term survival, respectively. Results A total of 989 participants were identified from the NHANES database. SI showed the diagnostic value of sarcopenia (tertile 1 vs. tertile 3: odds ratio [OR]=3.67, 95% confidence interval [CI]: 1.52–8.87, p=0.004; tertile 2 vs. tertile 3: OR=1.79, 95% CI: 0.75–4.28, p=0.191) adjusted for race, gender, and body mass index (BMI). Individuals with SI ≤ 68 had a poorer overall survival (OS) (hazard ratio [HR]=2.14, 95% CI: 1.71–2.68, p<0.001), and the RCS plot showed that the all-cause mortality risk gradually decreased with the increase in SI. Then, 203 patients with EC were enrolled, of which 76 patients were diagnosed with sarcopenia. There was a linear correlation between SI and skeletal muscle index and prealbumin, indicating that SI was reliable for diagnosing sarcopenia. Patients in the high sarcopenia risk group (Male: SI < 62; Female: SI < 55) showed a higher incidence of complications (OR=3.50, 95% CI: 1.85–6.61, p<0.001) and poorer long-term survival (HR=2.62, 95% CI: 1.02–6.77, p=0.046). Conclusion SI could be used to identify sarcopenia in patients with EC, and it is a useful prognostic factor of postoperative complications and long-term survival.