Coronavirus disease 2019 (COVID-19) is mainly an infectious disease of the respiratory system transmitted through air droplets, and pulmonary symptoms constitute main presentations of this disease. However, COVID-19 demonstrates a clinically diverse manifestation ranging from asymptomatic presentation to critically illness with severe pneumonia, acute respiratory distress syndrome, respiratory failure, or multiple organ failure. Accumulating evidences demonstrated that COVID-19 has extrapulmonary involvement, including neurological, smelling sensation, cardiovascular, digestive, hepatobiliary, renal, endocrinologic, dermatologic system, and others. Over a third of COVID-19 patients manifest a wide range of neurological symptoms involving the central/peripheral nervous system. Underlying cardiovascular comorbidities were associated with detrimental outcomes, meanwhile the occurrence of cardiovascular complications correlate to poor survival. Gastrointestinal symptoms frequently occur and have been associated with a longer period of illness. Impaired hepatic functions were associated with the severity of the disease. Higher rate of acute kidney injury was reported in critically ill patients with COVID-19. Endocrinologic presentations of COVID-19 include exacerbating hyperglycemia, euglycemic ketosis, and diabetic ketoacidosis. The most common cutaneous manifestation was acro-cutaneous (pernio or chilblain-like) lesions, and other skin lesions consist of maculopapular rash, vesicular lesions, livedoid/necrotic lesions, exanthematous rashes, and petechiae. This review article summarized the general clinical signs and symptoms, radiologic features, and disease manifestation with progression in patients with COVID-19.

Targeted degradation approaches such as proteolysis targeting chimeras (PROTACs) offer new ways to address disease through tackling challenging targets and with greater potency, efficacy, and specificity over traditional approaches. However, identification of high-affinity ligands to serve as PROTAC starting points remains challenging. As a complementary approach, we describe a class of molecules termed biological PROTACs (bioPROTACs)—engineered intracellular proteins consisting of a target-binding domain directly fused to an E3 ubiquitin ligase. Using GFP-tagged proteins as model substrates, we show that there is considerable flexibility in both the choice of substrate binders (binding positions, scaffold-class) and the E3 ligases. We then identified a highly effective bioPROTAC against an oncology target, proliferating cell nuclear antigen (PCNA) to elicit rapid and robust PCNA degradation and associated effects on DNA synthesis and cell cycle progression. Overall, bioPROTACs are powerful tools for interrogating degradation approaches, target biology, and potentially for making therapeutic impacts.

Non-alcoholic fatty liver disease (NAFLD) has been on a global rise. While animal models have rendered valuable insights to the pathogenesis of NAFLD, discrepancy with patient data still exists. Since non-alcoholic steatohepatitis (NASH) involves chronic inflammation, and CD4 + T cell infiltration of the liver is characteristic of NASH patients, we established and characterized a humanized mouse model to identify humanspecific immune response(s) associated with NAFLD progression. Immunodeficient mice engrafted with human immune cells (HIL mice) were fed with high fat and high calorie (HFHC) or chow diet for 20 weeks. Liver histology and immune profile of HIL mice were analyzed and compared with patient data. HIL mice on HFHC diet developed steatosis, inflammation and fibrosis of the liver. Human CD4 + central and effector memory T cells increased within the liver and in the peripheral blood of our HIL mice, accompanied by marked up-regulation of pro-inflammatory cytokines (IL-17A and IFNγ). In vivo depletion of human CD4 + T cells in HIL mice reduced liver inflammation and fibrosis, but not steatosis. Our results highlight CD4 + memory T cell subsets as important drivers of NAFLD progression from steatosis to fibrosis and provides a humanized mouse model for pre-clinical evaluation of potential therapeutics.

Hip fracture is an important health care issue in the elderly. Postoperative pulmonary complications occur in 4% of patients after hip fracture surgery. However, previous research is limited regarding pulmonary rehabilitation in this group. In this study, we present clinical evidence regarding the impact of a comprehensive pulmonary rehabilitation program in elderly hip fracture patients after hip surgery.We designed a nonrandomized, Quasi-experimental study, comparing 2 sequential time periods in the same center. Elderly patients (≥65 years) with a new hip fracture from February 1, 2014 to December 31, 2015 and who were willing to undergo a postoperative pulmonary rehabilitation program were enrolled. The pulmonary rehabilitation program started on January 1, 2015. Patients who refused rehabilitation or did not receive a surgical intervention were excluded. Patients received either standard care (standard care group) or standard care plus the postoperative rehabilitation program (intervention group).A total of 240 patients (163 women and 77 men) were enrolled, including 138 in the standard care group and 102 in the intervention group. The intervention group had a significantly lower incidence of pneumonia (6 patients, 5.9%) compared to the standard care group (19 patients, 13.9%). An age >80 years, cancer status, and not undergoing the postoperative pulmonary rehabilitation program were factors associated with a higher risk of pneumonia. In multivariate analysis, age >80 years, history of stroke/cancer, thrombocytopenia, and hyperglycemia (>200 mg/dL) were identified as risk factors for pneumonia.The incidence of pneumonia was lower in the elderly patients with hip fractures who received the postoperative pulmonary rehabilitation program after surgery. This is the first trial to demonstrate the effect of a postoperative pulmonary rehabilitation program in hip surgery patients.

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