Efficacy and safety of COVID-19 vaccines: a systematic review.

OBJECTIVE: To evaluate systematically the efficacy and safety of COVID-19 vaccines. METHODS: PubMed, Embase, Cochrane Library, Clinicaltrial.gov, CNKI, Wanfang Data, China Biomedical Literature Service System, and China Clinical Trial Registry were searched for randomized controlled trials of COVID-19 vaccines published up to December 31, 2020. The Cochrane bias risk assessment tool was used to assess the quality of studies. A qualitative analysis was performed on the results of clinical trials. RESULTS: Thirteen randomized, blinded, controlled trials, which involved the safety and efficacy of 11 COVID-19 vaccines, were included. In 10 studies, the 28-day seroconversion rate of subjects exceeded 80%. In two 10 000-scale clinical trials, the vaccines were effective in 95% and 70.4% of the subjects, respectively. The seroconversion rate was lower than 60% in only one study. In six studies, the proportion of subjects who had an adverse reaction within 28 days after vaccination was lower than 30%. This proportion was 30%-50% in two studies and > 50% in the other two studies. Most of the adverse reactions were mild to moderate and resolved within 24 hours after vaccination. The most common local adverse reaction was pain or tenderness at the injection site, and the most common systemic adverse reaction was fatigue, fever, or bodily pain. The immune response and incidence of adverse reactions to the vaccines were positively correlated with the dose given to the subjects. The immune response to the vaccines was worse in the elderly than in the younger population. In 6 studies that compared single-dose and double-dose vaccination, 4 studies showed that double-dose vaccination produced a stronger immune response than single-dose vaccination. CONCLUSIONS: Most of the COVID-19 vaccines appear to be effective and safe. Double-dose vaccination is recommended. However, more research is needed to investigate the long-term efficacy and safety of the vaccines and the influence of dose, age, and production process on the protective efficacy.

Real-time monitoring of hydrophobic aggregation reveals a critical role of cooperativity in hydrophobic effect.

The hydrophobic interaction drives nonpolar solutes to aggregate in aqueous solution, and hence plays a critical role in many fundamental processes in nature. An important property intrinsic to hydrophobic interaction is its cooperative nature, which is originated from the collective motions of water hydrogen bond networks surrounding hydrophobic solutes. This property is widely believed to enhance the formation of hydrophobic core in proteins. However, cooperativity in hydrophobic interactions has not been successfully characterized by experiments. Here, we quantify cooperativity in hydrophobic interactions by real-time monitoring the aggregation of hydrophobic solute (hexaphenylsilole, HPS) in a microfluidic mixer. We show that association of a HPS molecule to its aggregate in water occurs at sub-microsecond, and the free energy change is -5.8 to -13.6 kcal mol-1. Most strikingly, we discover that cooperativity constitutes up to 40% of this free energy. Our results provide quantitative evidence for the critical role of cooperativity in hydrophobic interactions.

Inhibition of ERK1/2 Signaling Pathway is Involved in Melatonin's Antiproliferative Effect on Human MG-63 Osteosarcoma Cells.

BACKGROUND: In a previous study, we found that melatonin inhibits MG-63 osteosarcoma cell proliferation; however, the underlying mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. AIMS: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin's antiproliferative actions on the human MG-63 osteosarcoma cells. METHODS/RESULTS: Western blot analysis confirmed that melatonin significantly inhibited phosphorylation of ERK1/2 but not p38, JNK, or Akt. The expression of ERK1/2, p38, JNK, and Akt was not altered by melatonin. PD98059 and melatonin alone, and especially in combination, significantly inhibited cell proliferation. The changes included G1 and G2/M phase arrest of the cell cycle, and a downregulation of the expression at both the protein and mRNA levels of cyclin D1 and CDK4 (related to the G1 phase) and of cyclin B1 and CDK1 (related to the G2/M phase) as measured by flow cytometry after propidium iodide staining, and both western blot and real-time PCR, respectively. Furthermore, the combination of PD98059 and melatonin synergistically and markedly augmented the action of either agent alone. Co-immunoprecipitation further confirmed that there was an interaction between p-ERK1/2 and cyclin D1, CDK4, cyclin B1, or CDK1, which was blunted in the presence of melatonin or PD98059. CONCLUSION: These findings suggest that melatonin's antiproliferative action is mediated by inhibition of the ERK1/2 signaling pathway rather than the p38, JNK, or Akt pathways.

Characterization of phosphorus leaching from phosphate waste rock in the Xiangxi River watershed, Three Gorges Reservoir, China.

Phosphate mining waste rocks dumped in the Xiangxi River (XXR) bay, which is the largest backwater zone of the Three Gorges Reservoir (TGR), are treated as Type I industry solid wastes by the Chinese government. To evaluate the potential pollution risk of phosphorus leaching from phosphate waste rocks, the phosphorus leaching behaviors of six phosphate waste rock samples with different weathering degrees under both neutral and acidic conditions were investigated using a series of column leaching experiments, following the Method 1314 standard of the US EPA. The results indicate that the phosphorus release mechanism is solubility-controlled. Phosphorus release from waste rocks increases as pH decreases. The phosphorus leaching concentration and cumulative phosphorus released in acidic leaching conditions were found to be one order of magnitude greater than that in neutral leaching conditions. In addition, the phosphorus was released faster during the period when environmental pH turned from weak alkalinity to slight acidity, with this accelerated release period appearing when L/S was in the range of 0.5-2.0 mL/g. In both neutral and acidic conditions, the average values of Total Phosphorus (TP), including orthophosphates, polyphosphates and organic phosphate, leaching concentration exceed the availability by regulatory (0.5 mg/L) in the whole L/S range, suggesting that the phosphate waste rocks stacked within the XXR watershed should be considered as Type II industry solid wastes. Therefore, the phosphate waste rocks deposited within the study area should be considered as phosphorus point pollution sources, which could threaten the adjacent surface-water environment.

Microsecond protein folding events revealed by time-resolved fluorescence resonance energy transfer in a microfluidic mixer.

We demonstrate the combination of the time-resolved fluorescence resonance energy transfer (tr-FRET) measurement and the ultrarapid hydrodynamic focusing microfluidic mixer. The combined technique is capable of probing the intermolecular distance change with temporal resolution at microsecond level and structural resolution at Angstrom level, and the use of two-photon excitation enables a broader exploration of FRET with spectrum from near-ultraviolet to visible wavelength. As a proof of principle, we used the coupled microfluidic laminar flow and time-resolved two-photon excitation microscopy to investigate the early folding states of Cytochrome c (cyt c) by monitoring the distance between the tryptophan (Trp-59)-heme donor-acceptor (D-A) pair. The transformation of folding states of cyt c in the early 500 µs of refolding was revealed on the microsecond time scale. For the first time, we clearly resolved the early transient state of cyt c, which is populated within the dead time of the mixer (<10 µs) and has a characteristic Trp-59-heme distance of ∼31 Å. We believe this tool can find more applications in studying the early stages of biological processes with FRET as the probe.

Visualizing millisecond chaotic mixing dynamics in microdroplets: A direct comparison of experiment and simulation.

In order to fully explore and utilize the advantages of droplet-based microfluidics, fast, sensitive, and quantitative measurements are indispensable for the diagnosis of biochemical reactions in microdroplets. Here, we report an optical detection technique using two-photon fluorescence lifetime imaging microscopy, with an aligning-summing and non-fitting division method, to depict two-dimensional (2D) maps of mixing dynamics by chaotic advection in microdroplets with high temporal and spatial resolution. The mixing patterns of two dye solutions inside droplets were quantitatively and accurately measured. The mixing efficiency in a serpentine droplet mixer was also quantified and compared with the simulation data. The mapped chaotic mixing dynamics agree well with the numerical simulation and theoretical prediction. This quantitative characterization is potentially applicable to the real-time kinetic study of biological and chemical reactions in droplet-based microfluidic systems.

Quantitative imaging of mixing dynamics in microfluidic droplets using two-photon fluorescence lifetime imaging.

Droplet-based microfluidic systems enable miniaturization of chemical reactions in femtoliter to picoliter volume compartments. Quantifying mixing dynamics of the reagents in droplets is critical to determine the system performance. In this Letter, we developed a two-photon excitation fluorescence lifetime imaging technique to quantitatively image the mixing dynamics in microfluidic droplets. A cross/autocorrelation method was used to reconstruct a high-quality fluorescence lifetime image of the droplet. The fluorescence decay was analyzed for accurate determination of the mixing ratio at each pixel of the image.