Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus  genus of the Pneumoviridae family in the order Mononegavirales. RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 years and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV's virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Humans ; Respiratory Syncytial Virus Infections/prevention & control* ; Respiratory Syncytial Viruses/pathogenicity* ; Respiratory Syncytial Virus, Human/pathogenicity* ; Antiviral Agents/therapeutic use*

ObjectiveTo investigate the influence of different diagnostic criteria on the short-term prognosis of patients with acute-on-chronic liver failure （ACLF）. MethodsA total of 115 ACLF patients who were hospitalized in Department of Gastroenterology， The Second Affiliated Hospital of Kunming Medical University， from January 2018 to January 2022 were enrolled， and all patients received internal medical treatment combined with artificial liver therapy. According to the guidelines， the patients were divided into CMA guideline group （Diagnostic and treatment guidelines for liver failure by Chinese Medical Association）（n=100）， APASL guideline group （Consensus statements of Asian Pacific Association for the Study of the Liver）（n=94）， and EASL guideline group （Criteria proposed by European Association for the Study of the Liver）（n=36）. The above three guidelines were compared in terms of 90-day mortality rate. A one-way analysis of variance was used for comprision of continuous date between groups； the chi-square test was used for comprision of categorical date between groups. The receiver operating characteristic （ROC） curve of related variables. ResultsThe 90-day mortality rate was 50.0% in the CMA guideline group， 51.1% in the APASL guideline group， and 77.8% in the EASL guideline group， and the EASL guideline group had a significantly higher 90-day mortality rate than the CMA guideline group （χ²=8.351， P=0.004） and the APASL guideline group （χ²=7.650， P=0.006）. EASL guideline had a sensitivity of 22.2% and a specificity of 92.3% in predicting the risk of short-term mortality， with an area under the ROC curve was 0.576. ConclusionACLF patients who meet EASL guideline tend to have a worse short-term prognosis， and this guideline may help to identify patients at a relatively high risk of short-term death.