Unveiling the Reaction Mechanism of Nitrate Reduction to Ammonia Over Cobalt-Based Electrocatalysts.

Electrocatalytic reduction of nitrate to ammonia (NRA) has emerged as an alternative strategy for sewage treatment and ammonia generation. Despite excellent performances having been achieved over cobalt-based electrocatalysts, the reaction mechanism as well as veritable active species across a wide potential range are still full of controversy. Here, we adopt CoP, Co, and Co3O4 as model materials to solve these issues. CoP evolves into a core@shell structured CoP@Co before NRA. For CoP@Co and Co catalysts, a three-step relay mechanism is carried out over superficial dynamical Coδ+ active species under low overpotential, while a continuous hydrogenation mechanism from nitrate to ammonia is unveiled over superficial Co species under high overpotential. In comparison, Co3O4 species are stable and steadily catalyze nitrate hydrogenation to ammonia across a wide potential range. As a result, CoP@Co and Co exhibit much higher NRA activity than Co3O4 especially under a low overpotential. Moreover, the NRA performance of CoP@Co is higher than Co although they experience the same reaction mechanism. A series of characterizations clarify the reason for performance enhancement highlighting that CoP core donates abundant electrons to superficial active species, leading to the generation of more active hydrogen for the reduction of nitrogen-containing intermediates.

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 µg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. RESULTS: The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. CONCLUSIONS: The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 µg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. RESULTS: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. CONCLUSIONS: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Identification and culture of functional salivary gland ductal epithelial cells.

Sialadenitis is a prevalent salivary gland disease resulting in decreased salivary flow rate. To date, little is known about the exact changes and mechanism of ductal cells in sialadenitis. This study aims to establish an efficient method to identify and isolate ductal cells, thereby facilitating further research on this specific cell type. Immunofluorescence for cytokeratin 13 and cytokeratin 19 was conducted in salivary glands to confirm their specificity as ductal cell markers. The dissected ducts were assessed through PCR and Western blot of cytokeratin 19 and digested by dispase and collagenase. The functionality of the isolated ductal cells was determined by measuring intracellular calcium. Cytokeratin 19 and cytokeratin 13 were expressed in all segments of human ducts. Cytokeratin 19 was limited to ducts excluding granular convoluted tubules in rat and mouse. The purities of the obtained ductal cells were approximately 98% in humans and 93% in rats. Furthermore, intracellular free calcium increased with time and concentration of carbachol treatment. Cytokeratin 19 serves as a dependable marker for identifying ductal cells in salivary glands, except for granular convoluted tubules. Moreover, we have successfully developed an efficient method for isolating ductal cells from salivary glands.

Targeted protein degradation combined with PET imaging reveals the role of host PD-L1 in determining anti-PD-1 therapy efficacy.

PURPOSE: Immunohistochemical staining of programmed death-ligand 1 (PD-L1) in tumor biopsies acquired through invasive procedures is routinely employed in clinical practice to identify patients who are most likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy. Nevertheless, PD-L1 expression is observed in various cellular subsets within tumors and their microenvironments, including tumor cells, dendritic cells, and macrophages. The impact of PD-L1 expression across these different cell types on the responsiveness to anti-PD-1 treatment is yet to be fully understood. METHODS: We synthesized polymer-based lysosome-targeting chimeras (LYTACs) that incorporate both PD-L1-targeting motifs and liver cell-specific asialoglycoprotein receptor (ASGPR) recognition elements. Small-animal positron emission tomography (PET) imaging of PD-L1 expression was also conducted using a PD-L1-specific radiotracer 89Zr-αPD-L1/Fab. RESULTS: The PD-L1 LYTAC platform was capable of specifically degrading PD-L1 expressed on liver cancer cells through the lysosomal degradation pathway via ASGPR without impacting the PD-L1 expression on host cells. When coupled with whole-body PD-L1 PET imaging, our studies revealed that host cell PD-L1, rather than tumor cell PD-L1, is pivotal in the antitumor response to anti-PD-1 therapy in a mouse model of liver cancer. CONCLUSION: The LYTAC strategy, enhanced by PET imaging, has the potential to surmount the limitations of knockout mouse models and to provide a versatile approach for the selective degradation of target proteins in vivo. This could significantly aid in the investigation of the roles and mechanisms of protein functions associated with specific cell subsets in living subjects.

Study on Water Splitting of the 214-Type Perovskite Oxides LnSrCoO4 (Ln = La, Pr, Sm, Eu, and Ga).

We present a study on the electrocatalysis of 214-type perovskite oxides LnSrCoO4 (Ln = La, Pr, Sm, Eu, and Ga) with semiconducting-like behavior synthesized using the sol-gel method. Among these five catalysts, PrSrCoO4 exhibits the optimal electrochemical performance in both the oxygen evolution reaction and the hydrogen evolution reaction, mainly due to its larger electrical conductivity, mass activity, and turnover frequency. Importantly, the weak dependency of LSV curves in a KOH solution with different pH values, revealing the adsorbate evolving mechanism in PrSrCoO4, and the density functional theory (DFT) calculations indicate that PrSrCoO4 has a smaller Gibbs free energy and a higher density of states near the Fermi level, which accelerates the electrochemical water splitting. The mutual substitution of different rare-earth elements will change the unit-cell parameters, regulate the electronic states of catalytic active site Co ions, and further affect their catalytic performance. Furthermore, the magnetic results indicate strong spin-orbit coupling in the electroactive sites of Co ions in SmSrCoO4 and EuSrCoO4, whereas the magnetic moments of Co ions in the other three catalysts mainly arise from the spin itself. Our experimental results expand the electrochemical applications of 214-type perovskite oxides and provide a good platform for a deeper understanding of their catalytic mechanisms.

A nomogram model for predicting intramyocardial hemorrhage post-PCI based on SYNTAX score and clinical features.

OBJECTIVE: The aim of this study is to develop a nomogram model for predicting the occurrence of intramyocardial hemorrhage (IMH) in patients with Acute Myocardial Infarction (AMI) following Percutaneous Coronary Intervention (PCI). The model is constructed utilizing clinical data and the SYNTAX Score (SS), and its predictive value is thoroughly evaluated. METHODS: A retrospective study was conducted, including 216 patients with AMI who underwent Cardiac Magnetic Resonance (CMR) within a week post-PCI. Clinical data were collected for all patients, and their SS were calculated based on coronary angiography results. Based on the presence or absence of IMH as indicated by CMR, patients were categorized into two groups: the IMH group (109 patients) and the non-IMH group (107 patients). The patients were randomly divided in a 7:3 ratio into a training set (151 patients) and a validation set (65 patients). A nomogram model was constructed using univariate and multivariate logistic regression analyses. The predictive capability of the model was assessed using Receiver Operating Characteristic (ROC) curve analysis, comparing the predictive value based on the area under the ROC curve (AUC). RESULTS: In the training set, IMH post-PCI was observed in 78 AMI patients on CMR, while 73 did not show IMH. Variables with a significance level of P < 0.05 were screened using univariate logistic regression analysis. Twelve indicators were selected for multivariate logistic regression analysis: heart rate, diastolic blood pressure, ST segment elevation on electrocardiogram, culprit vessel, symptom onset to reperfusion time, C-reactive protein, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, high-sensitivity troponin T (HS-TnT), and SYNTAX Score. Based on multivariate logistic regression results, two independent predictive factors were identified: HS-TnT (Odds Ratio [OR] = 1.61, 95% Confidence Interval [CI]: 1.21-2.25, P = 0.003) and SS (OR = 2.54, 95% CI: 1.42-4.90, P = 0.003). Consequently, a nomogram model was constructed based on these findings. The AUC of the nomogram model in the training set was 0.893 (95% CI: 0.840-0.946), and in the validation set, it was 0.910 (95% CI: 0.823-0.970). Good consistency and accuracy of the model were demonstrated by calibration and decision curve analysis. CONCLUSION: The nomogram model, constructed utilizing HS-TnT and SS, demonstrates accurate predictive capability for the risk of IMH post-PCI in patients with AMI. This model offers significant guidance and theoretical support for the clinical diagnosis and treatment of these patients.

Stabilizing Hydrogen Radicals in Two-Dimensional Cobalt-Copper Mesoporous Nanoplates for Complete Nitrate Reduction Electrocatalysis to Ammonia.

Ambient electrochemical reduction of waste nitrate (NO3-) represents an alternative green route for sustainable ammonia (NH3) electrosynthesis in water. Despites some encouraged achievements, sluggish eight electron and nine proton reduction routes that involve multi-step hydrogenation pathways have severely hindered their NH3 Faradaic efficiency (FENH3) and yield rate. Herein, we develop a robust two-dimensional mesoporous cobalt-copper (meso-CoCu) nanoplate electrocatalyst that delivers excellent performance of complete NO3- reduction reaction (NO3RR), including superior FENH3 of 98.8%, high NH3 yield rate of 3.39 mol h-1 g-1 and energy efficiency of 49.8%, and good cycling stability. Mechanism investigations unveil that active hydrogen (*H) radicals produced from water splitting on Co sites spillover to adjacent Cu sites and further stabilize within confined mesopores, which kinetically promote its coupling hydrogenation reactions of nitrogen intermediates and thus facilitate complete NO3RR for favorable NH3 electrosynthesis. Moreover, meso-CoCu nanoplates perform well as a bifunctional electrocatalyst in the two-electrode coupling system that concurrently synthesizes NH3 from NO3- at cathode and 2,5-furanedicarboxylic acid from 5-hydroxymethylfurfural at anode. This work in stabilizing *H radicals in mesoporous microenvironment provides some insights applied to various hydrogenation reactions for selective electrosynthesis of highly value-added chemicals in water.

Sorting Nexin1 negatively modulates phosphate uptake by facilitating Phosphate Transporter1;1 degradation in Arabidopsis.

High-affinity phosphate (Pi) transporters (PHTs) PHT1;1 and PHT1;4 are necessary for plant root Pi uptake especially under Pi-deficient conditions, but how their protein stability is modulated remains elusive. Here, we identified a Ttransfer DNA insertion mutant of Sorting Nexin1 (SNX1), which had more Pi content and less anthocyanin accumulation than the wild type under deficient Pi. By contrast, the snx1-2 mutant displayed higher sensitivity to exogenous arsenate in terms of seed germination and root elongation, revealing higher Pi uptake rates. Further study showed that SNX1 could co-localize and interact with PHT1;1 and PHT1;4 in vesicles and at the plasma membrane. Genetic analysis showed that increased Pi content in the snx1-2 mutant under low Pi conditions could be extensively compromised by mutating PHT1;1 in the double mutant snx1-2 pht1;1, revealing that SNX1 is epistatic to PHT1;1. In addition, SNX1 negatively controls PHT1;1 protein stability; therefore, PHT1;1 protein abundance in the plasma membrane was increased in the snx1-2 mutant compared with the wild type under either sufficient or deficient Pi. Together, our study (i) identifies SNX1 as a key modulator of the plant response to low Pi and (ii) unravels its role in the modulation of PHT1;1 protein stability, PHT1;1 accumulation at the plasma membrane, and root Pi uptake.

Entacapone alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is a common clinical problem and an efficacious treatment is lacking. Ferroptosis, a newly discovered type of programmed cell death, has been reported to alleviate renal tubular injury in ischemia/reperfusion-induced acute kidney injury (I/R-AKI). Entacapone is a specific inhibitor of catechol-O-methyltransferase, which is used as an adjuvant drug against Parkinson's disease. We demonstrated that entacapone prevents renal I/R injury by inhibiting ferroptosis. Compared with a sham group, entacapone treatment mitigated I/R-induced pathological alterations, improved renal function, and inhibited ferroptosis. In HK-2 cells, entacapone treatment significantly reduced the lipid peroxidation and iron accumulation induced by the ferroptosis inducers erastin and RSL3, and significantly regulated expression of ferroptosis-related proteins. Entacapone upregulates p62 expression and affects the p62-KEAP1-NRF2 pathway, thereby upregulating nuclear translocation of NRF2. This action results in increased expression of the downstream SLC7A11, and significant suppression of oxidative stress and ferroptosis. Our results identify entacapone as a ferroptosis inhibitor that enhances antioxidant capacity. Entacapone may serve as a novel strategy to improve treatment of, and recovery from, I/R-AKI.

Rodlike FeS/SnS@N-C Core-Shell Microparticles for Lithium-Ion Batteries.

FeS/SnS@N-C composites were successfully synthesized through the combination of nucleation self-assembly, N-doped carbon coating, and in situ vulcanization. The experimental results show that the discharge capacitance of FeS/SnS@N-C in the lithium storage process is 796.90 mAh g-1 at 0.5 A g-1 after 200 cycles, and more importantly, the discharge capacitance can maintain 278.84 mAh g-1 at 5 A g-1 after 2000 cycles. FeS in FeS/SnS@N-C plays a key role in the electrochemical performance, which is due to the certain electronic density of states (DOS) near the Fermi level. In short, our research expands the application of transition metal sulfide composites in lithium-ion batteries.

TiO2 nanoparticles modified graphitic carbon nitride with potential-resolved multicolor electrochemiluminescence and application for sensitive sensing of rutin.

Recently, nanocomposites with potential-resolved multicolor electrochemiluminescence (ECL) property have attracted new research interests. Herein, TiO2 nanoparticles modified graphitic carbon nitride (TiO2-NPs/g-C3N4) with inherent potential-resolved multicolor ECL emission was prepared via a simple synthesis method. The morphology and chemical composition of the synthesized TiO2-NPs/g-C3N4 were characterized. The obtained TiO2-NPs/g-C3N4 exhibited dual-peak multicolor ECL emission under cyclic voltammetry scanning by using K2S2O8 as co-reagent. The first ECL peak (ECL-1) is composed of turquoise blue ECL emission (471 nm) located at -1.3 V and olive green ECL emission (490 nm) ranging from -1.4 to -2.0 V. The second ECL peak (ECL-2) is composed of navy blue ECL emission (458 nm) located at -3.0 V. The ECL mechanism for the potential-resolved multicolor ECL emission was proposed. Furthermore, the first ECL imaging sensing method was fabricated for the sensitive quantitative detection of rutin based on the effective quenching effect of rutin on the ECL of TiO2-NPs/g-C3N4. The linear response range is 0.005-400 µM with detection limit as low as 2 nM. This work presents a simple way to prepare g-C3N4-based nanocomposites with potential-resolved multicolor ECL, which broadens the potential applications of g-C3N4-based nanocomposites for ECL imaging sensing and light-emitting devices.

An electrochemiluminescence resonance energy transfer biosensor based on CDs/PAMAM/rGO nanocomposites and Au@Ag2S nanoparticles for PML/RARα fusion gene detection.

In recent years, electrochemiluminescence resonance energy transfer (ECL-RET) with low background signal and high specificity has attracted much attention among researchers. Herein, we established a novel ECL-RET biosensor for PML/RARα fusion gene detection. In this ECL-RET system, carbon dots (CDs) with low toxicity and prominent electrochemical activity were used as donor and Au@Ag2S core-shell nanoparticles (Au@Ag2S NPs) were employed as ECL acceptor. The Au@Ag2S NPs possessed a wide ultraviolet-visible (UV-vis) absorption spectrum between 500 nm and 700 nm, which completely overlapped with the ECL spectrum of CDs. Furthermore, the CDs-decorated poly-amidoamine/reduced graphene oxide (CDs/PAMAM/rGO) nanocomposites were prepared to improve the ECL signals and served as a substrate to stably load capture probe deoxyribonucleic acid (DNA). Based on the ECL-RET biosensing strategy, the Au@Ag2S NPs-labeled assistant probes and target DNA could pair with capture probes to form the sandwich-type DNA structure and the distance between donor and accepter was closed, leading to quenching of the ECL signal of CDs. The ECL-RET biosensor represented eminent analytical performance for PML/RARα fusion gene detection with a wide linear relationship from 5 fM to 500 pM and a low detection limit of 0.72 fM, which provided a novel technical means and theoretical basis for detection and diagnosis of acute promyelocytic leukemia.

Stevioside reduces inflammation in periodontitis by changing the oral bacterial composition and inhibiting P. gingivalis in mice.

BACKGROUND: Excessive sugar intake has become a major challenge in modern societies. Stevioside is a promising non-calorie sweetener with anti-inflammatory effects; however, its effects on the oral environment and periodontitis remain unclear. Therefore, this study explores the effect of stevioside on periodontitis in mice. METHODS: Mice were divided into four groups, namely, control, treated with water, and periodontitis models, established using 5 - 0 silk sutures ligation around the second molar then infected the oral cavity with Porphyromonas gingivalis (P. gingivalis) viscous suspension, divided into three groups treated with 0.1% stevioside (P + S), 10% glucose (P + G), or water (P). Micro-CT scanning was used to assess alveolar bone resorption, while RT-PCR was used to evaluate the inflammatory factors expression and P. gingivalis invasion in the gingiva. The composition of the oral bacteria was analysed using 16 S rRNA sequence in the saliva. In addition, P. gingivalis was co-cultured with stevioside at different concentrations in vitro, and bacterial activity was detected via optical density values and live/dead staining. The virulence was detected using RT-PCR, while biofilm formation was detected using scanning electron microscopy. RESULTS: Compared with 10% glucose, treatment with 0.1% stevioside reduced alveolar bone absorption and osteoclasts while decreasing IL-6, TNF-α, IL-1ß, and P. gingivalis in the gingiva of periodontitis mice. The CEJ-ABC distance in the P + S group was significantly lower than that in the P and P + G groups (P < 0.05). Moreover, the composition of the oral bacteria in the P + S group was similar to that of the control. In vitro stevioside treatment also reduced the bacterial activity and toxicity of P. gingivalis in a dose-dependent manner and affected its biofilm composition. CONCLUSION: Our results indicate that, compared with 10% glucose, 0.1% stevioside intake can reduce alveolar bone resorption and inflammation in periodontal tissues in mice; the bacterial composition following 0.1% stevioside intake was similar to that of a healthy environment. In vitro, high concentrations of stevioside reduced P. gingivalis activity, biofilm formation, and virulence expression. Therefore, stevioside is a potential alternative to glucose for patients with periodontitis.

A New Segmented Virus Associated with Human Febrile Illness in China.

BACKGROUND: In 2017, surveillance for tickborne diseases in China led to the identification of a patient who presented to a hospital in Inner Mongolia with a febrile illness that had an unknown cause. The clinical manifestation of the illness was similar to that of tickborne encephalitis virus (TBEV) infection, but neither TBEV RNA nor antibodies against the virus were detected. METHODS: We obtained a blood specimen from the index patient and attempted to isolate and identify a causative pathogen, using genome sequence analysis and electron microscopy. We also initiated a heightened surveillance program in the same hospital to screen for other patients who presented with fever, headache, and a history of tick bites. We used reverse-transcriptase-polymerase-chain-reaction (RT-PCR) and cell-culture assays to detect the pathogen and immunofluorescence and neutralization assays to determine the levels of virus-specific antibodies in serum specimens from the patients. RESULTS: We found that the index patient was infected with a previously unknown segmented RNA virus, which we designated Alongshan virus (ALSV) and which belongs to the jingmenvirus group of the family Flaviviridae. ALSV infection was confirmed by RT-PCR assay in 86 patients from Inner Mongolia and Heilongjiang who presented with fever, headache, and a history of tick bites. Serologic assays showed that seroconversion had occurred in all 19 patients for whom specimens were available from the acute phase and the convalescent phase of the illness. CONCLUSIONS: A newly discovered segmented virus was found to be associated with a febrile illness in northeastern China. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China.).

Capsid Structure of Anabaena Cyanophage A-1(L).

A-1(L) is a freshwater cyanophage with a contractile tail that specifically infects Anabaena sp. PCC 7120, one of the model strains for molecular studies of cyanobacteria. Although isolated for half a century, its structure remains unknown, which limits our understanding on the interplay between A-1(L) and its host. Here we report the 3.35 Å cryo-EM structure of A-1(L) capsid, representing the first near-atomic resolution structure of a phage capsid with a T number of 9. The major capsid gp4 proteins assemble into 91 capsomers, including 80 hexons: 20 at the center of the facet and 60 at the facet edge, in addition to 11 identical pentons. These capsomers further assemble into the icosahedral capsid, via gradually increasing curvatures. Different from the previously reported capsids of known-structure, A-1(L) adopts a noncovalent chainmail structure of capsid stabilized by two kinds of mortise-and-tenon inter-capsomer interactions: a three-layered interface at the pseudo 3-fold axis combined with the complementarity in shape and electrostatic potential around the 2-fold axis. This unique capsomer construction enables A-1(L) to possess a rigid capsid, which is solely composed of the major capsid proteins with an HK97 fold. IMPORTANCE Cyanobacteria are the most abundant photosynthetic bacteria, contributing significantly to the biomass production, O2 generation, and CO2 consumption on our planet. Their community structure and homeostasis in natural aquatic ecosystems are largely regulated by the corresponding cyanophages. In this study, we solved the structure of cyanophage A-1(L) capsid at near-atomic resolution and revealed a unique capsid construction. This capsid structure provides the molecular details for better understanding the assembly of A-1(L), and a structural platform for future investigation and application of A-1(L) in combination with its host Anabaena sp. PCC 7120. As the first isolated freshwater cyanophage that infects the genetically tractable model cyanobacterium, A-1(L) should become an ideal template for the genetic engineering and synthetic biology studies.

Retinochoroidal microvascular changes in newly developed obese children: an optical coherence tomography angiography study.

BACKGROUND: Childhood obesity was associated with retinochoroidal microvascular changes using optical coherence tomography angiography (OCTA), but obesity duration was neglected. Obesity is chronic and progressive and obesity duration is related to microvascular function. Thus, it is important to identify microvascular changes in obese children timely to allow possible interventions with the increase in the number of obese children. This pilot study aimed to characterize retinochoroidal microvascular changes in newly developed obese children compared to age- and sex-matched controls. METHODS: Forty newly developed obese children and 40 age- and sex-matched controls were recruited. All subjects completed comprehensive eye examinations, including axial length, cycloplegic refraction, optical coherence tomography angiography scans (AngioVue; Optovue Inc), etc. RESULTS: There were no statistically significant differences between groups in terms of month age (P = 0.927), spherical equivalent refraction (P = 0.753) and axial length (P = 0.196). Newly developed obese children had lower vessel density (VD) in the inferior parafovea (P = 0.026), nasal parafovea (P = 0.038) and temporal perifovea (P = 0.026) of deep vascular complex (DVC), higher VD in the fovea of superficial vascular complex (P = 0.021) and the fovea of DVC (P = 0.016), and smaller foveal avascular zone (P = 0.003) when compared to controls. Also, no apparent differences in any quadrant of total retinal thickness, subfoveal choroidal thickness (SFCT), and choriocapillaries fow voids were detected (all P > 0.05). CONCLUSION: Retinochoroidal microvascular changes had already occurred in newly developed obese children, so early screening and close follow-up eye examinations were recommended; Retinal microvascular insult may precede its structural change and that retina may be a better candidate to predict the onset of retinochoroidal microvascular changes than choroid in obese children.

Clinical Endpoints for Evaluating Efficacy in COVID-19 Vaccine Trials.

Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) have entered or will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy of these vaccines, a general set of clinical endpoints is proposed, along with considerations to guide the selection of the primary endpoints on the basis of clinical and statistical reasoning. The plausibility that vaccine protection against symptomatic COVID-19 could be accompanied by a shift toward more SARS-CoV-2 infections that are asymptomatic is highlighted, as well as the potential implications of such a shift.

A Deferred-Vaccination Design to Assess Durability of COVID-19 Vaccine Effect After the Placebo Group Is Vaccinated.

Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur before longer-term efficacy and safety are known. The absence of a placebo group could compromise assessment of longer-term vaccine effects. However, by continuing follow-up after vaccination of the placebo group, this study shows that placebo-controlled vaccine efficacy can be mathematically derived by assuming that the benefit of vaccination over time has the same profile for the original vaccine recipients and the original placebo recipients after their vaccination. Although this derivation provides less precise estimates than would be obtained by a standard trial where the placebo group remains unvaccinated, this proposed approach allows estimation of longer-term effect, including durability of vaccine efficacy and whether the vaccine eventually becomes harmful for some. Deferred vaccination, if done open-label, may lead to riskier behavior in the unblinded original vaccine group, confounding estimates of long-term vaccine efficacy. Hence, deferred vaccination via blinded crossover, where the vaccine group receives placebo and vice versa, would be the preferred way to assess vaccine durability and potential delayed harm. Deferred vaccination allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain them on placebo, yet still allows important insights about immunologic and clinical effectiveness over time.

[Influence of processing factors on honey-fried Codonopsis Radix].

The present study investigated the influence of heating and honey addition on the appearance, chemical component content, and pharmacological activity of Codonopsis Radix decoction pieces in the honey-frying process, and explored the processing mechanism of honey-fried Codonopsis Radix. The color, sweetness, and content of macromolecular components(e.g., oligosaccharides and polysaccharides) and small molecular components(e.g., lobetyolin and atractylenolide Ⅲ) of raw Codonopsis Radix, fried Codonopsis Radix, honey-mixed Codonopsis Radix, and honey-fried Codonopsis Radix were determined, and the antioxidant activities in vitro of their water extract, polysaccharide extract, and oligosaccharide extract were compared. The results showed that in terms of color and sweetness, compared with the raw Codonopsis Radix, the fried Codonopsis Radix slightly changed, the honey-mixed Codonopsis Radix changed significantly, and the honey-fried Codonopsis Radix changed with high significance. In terms of the content of lobetyolin, atractylenolide Ⅲ, and polysaccharides, the samples were ranked as raw Codonopsis Radix > fried Codonopsis Radix > honey-mixed Codonopsis Radix > honey-fried Codonopsis Radix, which indicated that heating and honey addition could reduce the content of these three components. In terms of the content of oligosaccharides, the samples were ranked as honey-fried Codonopsis Radix ≈ honey-mixed Codonopsis Radix > fried Codonopsis Radix ≈ raw Codonopsis Radix, indicating that honey addition could increase the content of oligosaccharides. In terms of antioxidant activity in vitro, ABTS radical scavenging ability of water extract, polysaccharides, and oligosaccharides of honey-fried Codonopsis Radix was most potent, while the change of antioxidant activity in vitro of each extract in the other three processed products was different. In short, both heating and honey addition can affect the appearance, chemical component content, and antioxidant activity in vitro of Codonopsis Radix decoction pieces, but the effect of the combination of the two factors is the best. The comprehensive analysis of the effects of heating and honey addition on Codonopsis Radix decoction pieces indicates that honey addition followed by heating at high temperature is the necessary condition for honey-fried Codonopsis Radix to enhance its activity.