Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells. Here, we designed a nanomotor with integrated fluorescence and therapeutic potential based on biodegradable polymersomes equipped with aggregation-induced emission (AIE) agents. The AIE segments provided the polymersomes with autofluorescence, facilitating the visualization of cell uptake. Furthermore, the membrane structure enabled the reshaping of the AIE polymersomes into asymmetric, peanut-shaped polymersomes. Upon laser irradiation, these peanut polymersomes not only displayed fluorescence, but also produced reactive oxygen species (ROS). Because of their specific shape, the ROS gradient induced motility in these particles. As ROS is also used for cancer cell treatment, the peanut polymersomes not only acted as delivery vehicles but also as therapeutic agents. As an integrated platform, these peanut polymersomes therefore represent an interesting delivery system with biomedical potential.</p

Inherently Fluorescent Peanut-Shaped Polymersomes for Active Cargo Transportation

Nanomotors have been extensively explored for various applications in nanomedicine, especially in cargo transportation. Motile properties enable them to deliver pharmaceutical ingredients more efficiently to the targeted site. However, it still remains a challenge to design motor systems that are therapeutically active and can also be effectively traced when taken up by cells. Here, we designed a nanomotor with integrated fluorescence and therapeutic potential based on biodegradable polymersomes equipped with aggregation-induced emission (AIE) agents. The AIE segments provided the polymersomes with autofluorescence, facilitating the visualization of cell uptake. Furthermore, the membrane structure enabled the reshaping of the AIE polymersomes into asymmetric, peanut-shaped polymersomes. Upon laser irradiation, these peanut polymersomes not only displayed fluorescence, but also produced reactive oxygen species (ROS). Because of their specific shape, the ROS gradient induced motility in these particles. As ROS is also used for cancer cell treatment, the peanut polymersomes not only acted as delivery vehicles but also as therapeutic agents. As an integrated platform, these peanut polymersomes therefore represent an interesting delivery system with biomedical potential.</p

Efficacy, safety, and immunogenicity of SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012: a randomized, double-blind, placebo-controlled phase 3 trial

BackgroundWe aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China.MethodsThis is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention.Results2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals.ConclusionThe LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period.Clinical trial registrationClinicalTrials.gov, identifier NCT05745545

A Study on Thermal Performance of a Novel All-Glass Evacuated Tube Solar Collector Manifold Header with an Inserted Tube

A novel all-glass evacuated tube collector manifold header with an inserted tube is proposed in this paper which makes water in all-glass evacuated solar collector tube be forced circulated to improve the performance of solar collector. And a dynamic numerical model was presented for the novel all-glass evacuated tube collector manifold header water heater system. Also, a test rig was built for model validation and comparison with traditional all-glass evacuated tube collector. The experiment results show that the efficiency of solar water heater with a novel collector manifold header is higher than traditional all-glass evacuated tube collector by about 5% and the heat transfer model of water heater system is valid. Based on the model, the relationship between the average temperature of water tank and inserted tube diameter (water mass flow) has been studied. The results show that the optimized diameter of inserted tube is 32 mm for the inner glass with the diameter of 47 mm and the water flow mass should be less than 1.6 Kg/s

Comparison of three sample size calculation methods for non-inferiority vaccine trials with multiple continuous co-primary endpoints

Clinical trials that study immunogenicity of combination vaccines often have less power than desirable. To make up for the reduction in statistical power at the study level, researchers have to increase the study sample size. To study immunogenicity variables, we used the geometric mean concentration of immune response after vaccination as immunologic endpoint and compared 3 sample size calculation methods: the “Inflation factors” method, the “Incrementing” method, and the “Bonferroni correction” method when there are multiple continuous co-primary endpoints. The parameters were set according to the actual situation of the use of combination vaccines and the simulation results were used as reference. The present study demonstrates that all 3 methods are applicable when the effect size of each endpoint is similar and the endpoints are at most weakly correlated, but when there is a true difference in effect sizes among endpoints, the “Incrementing” method has the best performance

Long-Term Prognostic Value of Myocardial Viability by Myocardial Contrast Echocardiography in Patients after Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

Background and Objectives: According to recent guidelines, myocardial contrast echocardiography (MCE) is recommended for detecting residual myocardial viability (MV). However, the long-term prognostic value of MV as assessed by MCE in identifying major adverse cardiac events (MACE) after acute myocardial infarction (AMI) remains undefined. Materials and Methods: We searched multiple databases, including PubMed, EMBASE, and Web of Science for studies on the prognostic value of MCE for clinical outcomes in AMI patients. The primary endpoints were MACEs during follow-up. Six studies that evaluated a total of 536 patients with a mean follow-up of 36.8 months were reviewed. Results: The pooled sensitivity and specificity of MCE for predicting MACEs were 0.80 and 0.78, respectively, and the summary operating receiver characteristics achieved an area under the curve of 0.84. The pooled relative risks demonstrated that the MV evaluated by MCE after AMI was correlated with a high risk for total cardiac events (pooled relative risk: 2.07; 95% confidence interval: 1.28&ndash;3.37) and cardiac death (pooled relative risk: 2.48; 95% confidence interval: 1.03&ndash;5.96). MV evaluated by MCE was a highly independent predictor of total cardiac events (pooled hazard ratio: 2.09, 95% confidence interval: 1.14&ndash;3.81) in patients after AMI. Conclusions: Residual MV evaluated by MCE may be an effective long-term prognostic tool for predicting MACE in patients after AMI that can provide moderate predictive accuracy. The assessment of MV by MCE may become an alternative technique with the potential to rapidly provide important information for improving long-term risk stratification in patients after AMI, at the bedside in clinical practice, especially for patients who cannot tolerate prolonged examinations. The PROSPERO registration number is CRD42020167565

A novel SLC6A8 mutation associated with intellectual disabilities in a Chinese family exhibiting creatine transporter deficiency: case report

Abstract Background X-linked creatine transporter deficiency (OMIM#300036,CRTR-D) is characterized by cerebral creatine deficiency, intellectual disabilities, severe speech impairment, seizures and behavioral problems. Mutations in the creatine transporter gene SLC6A8, a member of the solute-carrier family 6 mapped to Xq28, have been reported to cause the creatine transporter deficiency. Case presentation The proband presented at 5 yrs. 1 month of age with delays in intellectual and development, seizures and behavioral problems. A novel missense mutation, c.1181C > A (p.Thr394Lys), in the SLC6A8 gene (NM_005629.3) was detected via targeted exome sequencing, and then validated by Sanger sequencing. Multiple in silico variant effect analysis methods, including SIFT, PolyPhen2, PROVEAN, and Mutation Taster predicted that this variant was likely damaging or diseasing-causing. This hemizygous variation was also identified in the affected brother with the same clinical condition and inherited from the heterozygous carrier mother. The diagnosis was suggested by increased urinary creatine/creatinine (Cr:Crn) ratio and markedly reduced creatine content peak by brain proton magnetic resonance spectroscopy (MRS). The proband’s mother became pregnant with a 3rd sibling, in whom the Sanger sequencing result of c.1181C > A was negative. Conclusion The novel mutation c.1181C > A in the SLC6A8 gene reported in a Chinese family has expanded the mutation spectrum of CRTR-D. The combination of powerful new technologies such as targeted exome sequencing with thorough systematic clinical evaluation of patients will improve the diagnostic yield, and assist in genetic counselling and prenatal diagnosis for suspected genetic disorders

Regional Impacts of ENSO on Summer Precipitation along the Chinese Coast

Rainfall and sea surface temperature grid data, as well as rainfall data from coastal stations in China, were used to obtain the spatiotemporal response characteristics of summer rainfall along the Chinese coast to ENSO and analyzed interdecadal changes in summer rainfall. The results show that: (1) Summer rainfall along the coast of China was significantly affected by ENSO and can be divided into three regions, with Lianyungang and Yunao as the boundaries. The Niño3.4 index was negatively correlated with summer rainfall along the Bohai and Yellow Sea coasts, positively correlated with that of the East China Sea coast, and not significantly correlated with that of the South China Sea coast. (2) On an interdecadal timescale, the relationship between summer rainfall along the coast of China and the Niño3.4 index was unstable. The negative correlation between summer rainfall along the Bohai and Yellow Sea coasts and the Niño3.4 index was significant before and after 1980 and 2010, respectively. The positive correlation along the East China Sea coast became insignificant after the 1980s, whereas the correlation along the South China Sea coast remained insignificant. (3) On the interdecadal timescale, the summer Niño3.4 index, winter Arctic Oscillation (AO) index in the previous year, and spring Antarctic Oscillation (AAO) index in current year were significantly negatively correlated with summer interdecadal rainfall along the Bohai and Yellow Sea coasts and positively correlated with summer interdecadal rainfall along the East China Sea coast. Summer interdecadal rainfall along the coast of the South China Sea was significantly negatively correlated with the spring Arctic Sea ice index in the current year. Regarding the Niño3.4 index, the high sea surface temperature in the Central and Eastern Pacific triggered a negative Pacific-Japan-type interconnection wave train in the 500 hPa geopotential height field, resulting in a decrease in interdecadal rainfall along the Bohai and Yellow Sea coast and an increase in interdecadal rainfall along the East China Sea coast. When the winter AO in the last year and spring AAO in the current year were in a positive phase, the abnormal anticyclone in the southern part of Baikal Lake at 850 hPa wind field guided the airflow in the mid to high latitudes southward, causing a weakening of the East Asian summer monsoon and a decrease in interdecadal summer rainfall along the Bohai and Yellow Sea. In addition, the strong, westward position of the subtropical high pressure in the northwest Pacific increases the upward movement, increasing interdecadal summer rainfall along the East China Sea coast. The interdecadal variation of spring Arctic Sea ice stimulates the opposite atmospheric circulation pattern that induced interdecadal variation of summer rainfall along the South China Sea coast in the 850 hPa wind and 500 hPa geopotential height fields