Study on the epoxidation of chain olefins using biquaternary ammonium phosphotungstic acid phase transfer catalysts under no-solvent condition.

In this study, we have developed a novel catalyst synthesized by phosphotungstic acid and a gemini quaternary ammonium cation salt. This quaternary ammonium salt not only reduces the interfacial tension between olefins and hydrogen peroxide but also forms a notably stable structure with phosphotungstic acid. Dodecene was successfully epoxidized to epoxy dodecane with a selectivity of 82.9 %. The impact of initial conditions was systematically investigated such as molar ratio, temperature, reaction time, and catalyst dosage on the catalytic performance. Characterization of the catalyst morphology was performed by SEM, TEM and SAXS. Raman spectra, FT-IR and XPS spectra were employed to perform the catalyst transformation during the epoxidation reaction. This catalytic mechanism study could provide the industrial application in the epoxidation of long-chain olefins.

Probing the Electron Accepting Ability of Phosphaphenalenes.

Phosphaphenalenes, extended π conjugates with the incorporation of phosphorus, are attractive avenues towards molecular materials for the applications in organic electronics, but their electron accepting ability have not been investigated. In this study, we present systematic studies on the reductive behavior of a representative phosphaphenalene and its oxide by chemical and electrochemical methods. The chemical reduction of the phosphaphenalene by alkali metals reveals the facile P‒C bond cleavage to form phosphaphenalenide anion, which functions as a transfer block for structure modification on the phosphorus atom. In contrast, the pentavalent P-oxide reacts with one or two equivalents of elemental sodium to form stable radical anion and dianion salts, respectively.

TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis.

TRIM21 is a RING finger domain-containing ubiquitin E3 ligase whose expression is elevated in autoimmune disease. While TRIM21 plays an important role in immune activation during pathogen infection, little is known about its inherent cellular function. Here we show that TRIM21 plays an essential role in redox regulation by directly interacting with SQSTM1/p62 and ubiquitylating p62 at lysine 7 (K7) via K63-linkage. As p62 oligomerizes and sequesters client proteins in inclusions, the TRIM21-mediated p62 ubiquitylation abrogates p62 oligomerization and sequestration of proteins including Keap1, a negative regulator of antioxidant response. TRIM21-deficient cells display an enhanced antioxidant response and reduced cell death in response to oxidative stress. Genetic ablation of TRIM21 in mice confers protection from oxidative damages caused by arsenic-induced liver insult and pressure overload heart injury. Therefore, TRIM21 plays an essential role in p62-regulated redox homeostasis and may be a viable target for treating pathological conditions resulting from oxidative damage.

Aurora A-mediated pyruvate kinase M2 phosphorylation promotes biosynthesis with glycolytic metabolites and tumor cell cycle progression.

Cancer cells have distinctive demands for intermediates from glucose metabolism for biosynthesis and energy in different cell cycle phases. However, how cell cycle regulators and glycolytic enzymes coordinate to orchestrate the essential metabolic processes are still poorly characterized. Here, we report a novel interaction between the mitotic kinase, Aurora A, and the glycolytic enzyme, pyruvate kinase M2 (PKM2), in the interphase of the cell cycle. We found Aurora A-mediated phosphorylation of PKM2 at threonine 45. This phosphorylation significantly attenuated PKM2 enzymatic activity by reducing its tetramerization and also promoted glycolytic flux and the branching anabolic pathways. Replacing the endogenous PKM2 with a nonphosphorylated PKM2 T45A mutant inhibited glycolysis, glycolytic branching pathways, and tumor growth in both in vitro and in vivo models. Together, our study revealed a new protumor function of Aurora A through modulating a rate-limiting glycolytic enzyme, PKM2, mainly during the S phase of the cell cycle. Our findings also showed that although both Aurora A and Aurora B kinase phosphorylate PKM2 at the same residue, the spatial and temporal regulations of the specific kinase and PKM2 interaction are context dependent, indicating intricate interconnectivity between cell cycle and glycolytic regulators.

Estrogen increases the expression of BKCa and impairs the contraction of colon smooth muscle via upregulation of sphingosine kinase 1.

Estrogen (E2) may impair the contraction of colonic smooth muscle (SM) leading to constipation. Large conductance Ca2+ -activated K+ channels (BKCa ) are widely expressed in the smooth muscle cells (SMCs) contributing to hyperpolarization and relaxation of SMCs. Sphingosine kinase 1 (SphK1) is known to influence the expression of BKCa . We aimed to elucidate the potential underlying molecular mechanism of BKCa and SphK1 that may influence E2-induced colonic dysmotility. In ovariectomized rats, SM contraction and expression of BKCa , SphK1, sphingosine-1-phosphate receptor (S1PR) were analyzed after the treatment with vehicle, BSA-E2, E2, and E2 receptor antagonist. The role of BKCa , SphK1, and S1PR in E2-induced SM dysmotility was investigated in rat colonic SMCs. The effect of SphK1 on SM contraction as well as on the expression of BKCa and S1PR was analyzed in SphK1 knock-out mutant mice and wild-type (WT) mice treated with or without E2. The E2-treated group exhibited a weak contraction of colonic SM and a delayed colonic transit. The treatment with E2 significantly upregulated the expression of BKCa , SphK1, S1PR1, and S1PR2, but not S1PR3, in colon SM and SMCs. Inhibition of BKCa , SphK1, S1PR1, and S1PR2 expression attenuated the effect of E2 on Ca2+ mobilization in rat colon SMCs. WT mice treated with E2 showed impaired gastrointestinal motility and enhanced expression of BKCa , S1PR1, and S1PR2 compared with those without E2 treatment. Conversely, in SphK1 knock-out mice treated with E2, these effects were partially reversed. E2 increased the release of S1P which in turn could have activated S1PR1 and S1PR2. Loss of SphK1 attenuated the effect of E2 on the upregulation of S1PR1 and S1PR2 expression. These findings indicated that E2 impaired the contraction of colon SM through activation of BKCa via the upregulation of SphK1 and the release of S1P. In the E2-induced BKCa upregulation, S1PR1 and S1PR2 might also be involved. These results may provide further insights into a therapeutic target and optional treatment approaches for patients with constipation.

Association between cadmium exposure and pulmonary function reduction: Potential mediating role of telomere attrition in chronic obstructive pulmonary disease patients.

BACKGROUND: Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear. METHODS: All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS). RESULTS: Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively. CONCLUSION: Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.

Molecular Regulatory Network of Anthocyanin Accumulation in Black Radish Skin as Revealed by Transcriptome and Metabonome Analysis.

To understand the coloring mechanism in black radish, the integrated metabolome and transcriptome analyses of root skin from a black recombinant inbred line (RIL 1901) and a white RIL (RIL 1911) were carried out. A total of 172 flavonoids were detected, and the analysis results revealed that there were 12 flavonoid metabolites in radish root skin, including flavonols, flavones, and anthocyanins. The relative concentrations of most flavonoids in RIL 1901 were higher than those in RIL 1911. Meanwhile, the radish root skin also contained 16 types of anthocyanins, 12 of which were cyanidin and its derivatives, and the concentration of cyanidin 3-o-glucoside was very high at different development stages of black radish. Therefore, the accumulation of cyanidin and its derivatives resulted in the black root skin of radish. In addition, a module positively related to anthocyanin accumulation and candidate genes that regulate anthocyanin synthesis was identified by the weighted gene co-expression network analysis (WGCNA). Among them, structural genes (RsCHS, RsCHI, RsDFR, and RsUGT75C1) and transcription factors (TFs) (RsTT8, RsWRKY44L, RsMYB114, and RsMYB308L) may be crucial for the anthocyanin synthesis in the root skin of black radish. The anthocyanin biosynthesis pathway in the root skin of black radish was constructed based on the expression of genes related to flavonoid and anthocyanin biosynthesis pathways (Ko00941 and Ko00942) and the relative expressions of metabolites. In conclusion, this study not only casts new light on the synthesis and accumulation of anthocyanins in the root skin of black radish but also provides a molecular basis for accelerating the cultivation of new black radish varieties.

Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection.

Early detection can benefit cancer patients with more effective treatments and better prognosis, but existing early screening tests are limited, especially for multi-cancer detection. This study investigated the most prevalent and lethal cancer types, including primary liver cancer (PLC), colorectal adenocarcinoma (CRC), and lung adenocarcinoma (LUAD). Leveraging the emerging cell-free DNA (cfDNA) fragmentomics, we developed a robust machine learning model for multi-cancer early detection. 1,214 participants, including 381 PLC, 298 CRC, 292 LUAD patients, and 243 healthy volunteers, were enrolled. The majority of patients (N = 971) were at early stages (stage 0, N = 34; stage I, N = 799). The participants were randomly divided into a training cohort and a test cohort in a 1:1 ratio while maintaining the ratio for the major histology subtypes. An ensemble stacked machine learning approach was developed using multiple plasma cfDNA fragmentomic features. The model was trained solely in the training cohort and then evaluated in the test cohort. Our model showed an Area Under the Curve (AUC) of 0.983 for differentiating cancer patients from healthy individuals. At 95.0% specificity, the sensitivity of detecting all cancer reached 95.5%, while 100%, 94.6%, and 90.4% for PLC, CRC, and LUAD, individually. The cancer origin model demonstrated an overall 93.1% accuracy for predicting cancer origin in the test cohort (97.4%, 94.3%, and 85.6% for PLC, CRC, and LUAD, respectively). Our model sensitivity is consistently high for early-stage and small-size tumors. Furthermore, its detection and origin classification power remained superior when reducing sequencing depth to 1× (cancer detection: ≥ 91.5% sensitivity at 95.0% specificity; cancer origin: ≥ 91.6% accuracy). In conclusion, we have incorporated plasma cfDNA fragmentomics into the ensemble stacked model and established an ultrasensitive assay for multi-cancer early detection, shedding light on developing cancer early screening in clinical practice.

Kirsten rat sarcoma viral oncogene homolog G12C mutant advanced non-small-cell lung cancer treated with MEK1/2 inhibitor trametinib: a case report.

No targeted therapies are approved for non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation to date. Trametinib, a selective allosteric inhibitor of the MEK1/2, demonstrated debatable clinical activity in KRAS-mutant NSCLC. In this case, we present a recurrent advanced NSCLC with KRAS G12C mutation successfully treated with single-agent trametinib therapy. An 87-year-old man who underwent radiotherapy for the right lung adenocarcinoma was admitted to clinical oncology center for recurrent lesions in bilateral lungs. He was unwilling to perform second-line chemotherapy, but underwent molecular profiling and revealed the KRAS G12C mutation. The single-agent target therapy of trametinib showed clinical benefit without obvious toxicity. Furthermore, this report reviewed the previous date of the preclinical and clinical and summarized that KRAS G12C mutation may be more sensitive to the inhibition of mitogen-activated protein kinase kinase. This case advocates for routine screening of KRAS point mutations in the utility of precision medicine and suggests that treatment with trametinib in advanced NSCLC cases with KRAS G12C mutation is well tolerated and effective, especially for those very elderly or unsuitable for more aggressive chemotherapy.

Clinical value of positive BET and pelvic floor dyssynergia in Chinese patients with functional defecation disorder.

BACKGROUND: Functional defecation disorder (FDD) is a common subtype of functional constipation (FC). Balloon expulsion test (BET) and high resolution anorectal manometry (HR-ARM) are significant tools but their results are not always consistent. AIMS: To investigate the characteristics of patients with positive BET and pelvic floor dyssynergia (PFD) and explore the value of both positive results in FDD diagnosis. METHODS: We retrospectively diagnosed FC subtypes and enrolled FDD patients based on Rome-IV criteria. They underwent HR-ARM, BET and CTT tests. Then they were classified to two groups and further stratified by FDD subtypes. Validated questionnaires were applied to investigate patients' constipation, anxiety/depression and quality of life. RESULTS: 335 FDD patients were finally enrolled. They were classified into two groups according to whether BET and PFD were both positive (consistent or not). 84.48% showed consistent results. These patients had significantly higher anal residual pressure, lower anal relaxation rate, manometric defecation index (MDI) and a more negative rectoanal pressure gradient (RAPG) (Ps < .05). The specific distribution of FDD phenotypes in two groups showed significant difference (p = .021). Males suffered a more negative RAPG (p < .001) and age was correlated with anal relaxation rate (p < .001). A subset (177 individuals) was investigated with validated questionnaires. Scores for Defecation Symptoms, Physical Discomfort and GAD-7 score were significantly high in Consistent Group (Ps < .05). GAD-7 score was associated with Defecation Symptoms (p < .001) while anal residual pressure, GAD-7 and Defecation Symptoms score were linked to Physical Discomfort (Ps < .05). The diagnostic specificity and PPV for FDD rose significantly with positive BET and PFD. CONCLUSION: FDD patients with positive BET and PFD suffered from severe defecation symptoms, anxiety and impaired QOL. Positive BET and PFD could be an ideal tool for screening FDD.

Valuation of ecosystem damage induced by soil-groundwater pollution in an arid climate area: Framework, method and case study.

Groundwater is an important source of water, even the only source in some arid areas. However, climate changing and ecosystem damage induced by pollution aggravate water resource crisis. The "polluter pays" principle is deeply rooted in efforts to manage the polluted sites, particularly in the soil-groundwater environment. Unfortunately, there is no ecosystem damage compensation mechanism generally accepted by all stakeholders. In this study, we establish an assessment framework and valuation methods for ecosystem damage induced by soil-groundwater pollution in an arid climate area based on a "pollution source → target (soil-groundwater) → receptor (humans, animals, and plants) → damages → stakeholders (human society and ecosystem)" model that is usually applied in groundwater risk assessment research. Five economic loss are included in the valuation methods: (1) human health loss, (2) emergency disposal cost, (3) direct economic loss, (4) ecological restoration cost, and (5) ecosystem services loss. We apply the framework to a case study in an arid climate area, northwest China and calculate the total economic loss from ecosystem damage in the case study at 12.6 million yuan. The largest proportion of the total loss was the ecological restoration cost (85.6%), followed by the emergency disposal cost (11.2%), and finally ecosystem services loss (3.2%). Valuation of ecosystem damage from environmental pollution is essentially a socioeconomic issue. This study supplies a new framework and methods for valuing ecosystem damage induced by pollution, and offers suggestions for environmental management to reduce the damage caused by soil-groundwater pollution to health and ecosystems.

Perceptions of exercise and exercise instruction in patients with type 2 diabetes mellitus and sarcopenia : a qualitative study.

BACKGROUND: Exercise plays a major role in helping patients with type 2 diabetes mellitus and sarcopenia to increase muscle mass and muscle strength. However, little is known about perceptions of exercise and exercise instruction in these patients. This study aimed to explore the perceptions of exercise and exercise instruction from the patient's perspective. METHODS: In a descriptive qualitative study, semi-structured face-to-face in-depth interviews were conducted with 16 patients with type 2 diabetes mellitus and sarcopenia at a tertiary hospital. The Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines were followed to ensure rigor in the study. The interviews were analysed using a thematic analysis method. RESULTS: Four themes and 13 sub-themes were identified in this study. The four themes were knowledge-attitudes-practices surrounding exercise, motivators and barriers regarding exercise, and attitudes towards professional exercise instruction. CONCLUSION: This study provides a detailed understanding of the knowledge-attitudes-practices, motivators and barriers regarding exercise among patients with type 2 diabetes mellitus and sarcopenia, as well as attitudes related to exercise instruction. The current findings can guide healthcare professionals, patients' families, and policymakers to motivate patients to be physically active through policy initiatives and other types of incentives and programmes, such as providing more health education and holistic support, increasing family and friends' companionship and care, and providing suitable exercise conditions.

Robust partitioning of microRNA targets from downstream regulatory changes.

The biological impact of microRNAs (miRNAs) is determined by their targets, and robustly identifying direct miRNA targets remains challenging. Existing methods suffer from high false-positive rates and are unable to effectively differentiate direct miRNA targets from downstream regulatory changes. Here, we present an experimental and computational framework to deconvolute post-transcriptional and transcriptional changes using a combination of RNA-seq and PRO-seq. This novel approach allows us to systematically profile the regulatory impact of a miRNA. We refer to this approach as CARP: Combined Analysis of RNA-seq and PRO-seq. We apply CARP to multiple miRNAs and show that it robustly distinguishes direct targets from downstream changes, while greatly reducing false positives. We validate our approach using Argonaute eCLIP-seq and ribosome profiling, demonstrating that CARP defines a comprehensive repertoire of targets. Using this approach, we identify miRNA-specific activity of target sites within the open reading frame. Additionally, we show that CARP facilitates the dissection of complex changes in gene regulatory networks triggered by miRNAs and identification of transcription factors that mediate downstream regulatory changes. Given the robustness of the approach, CARP would be particularly suitable for dissecting miRNA regulatory networks in vivo.

Screening and identification of novel candidate biomarkers of focal cortical dysplasia type II via bioinformatics analysis.

PURPOSE: Focal cortical dysplasia (FCD) is the most common developmental malformation that causes refractory epilepsy. FCD II is a common neuropathological finding in tissues resected therapeutically from patients with drug-resistant epilepsy. However, its molecular genetic etiology remains unclear. This study aimed to identify potential molecular markers of FCD II using bioinformatics analysis. METHODS: We downloaded two datasets for FCD II from the Gene Expression Omnibus data repository. Differentially expressed genes (DEGs) between FCD II and normal brain tissues were identified, and functional enrichment analysis was performed. A protein-protein interaction network was constructed, and hub genes were identified from the DEGs. The hub gene expression was validated using WB in vitro. IHC staining was performed to verify the feasibility of the target molecular markers identified in the bioinformatics analysis. RESULTS: One hundred sixty-seven common DEGs were identified between the datasets. The GO and KEGG analyses showed that variations were prominently enriched in some functions associated with gene expression. Five hub genes (i.e., FANCI, FANCA, BRCA2, RAD18, and KEAP1) were identified. Western blotting confirmed that all hub gene expressions were higher in the FCD II tissue than in the normal brain tissue. IHC staining showed that the FANCI expression significantly increased in the FCD II tissue. CONCLUSION: There are DEGs between FCD II and normal brain tissues, which may be considered biomarkers for FCD II, along with FANCI. The DEGs and hub genes identified in the bioinformatics analysis could serve as candidate targets for diagnosing and treating FCD II.

Serum cadmium positively correlates with inflammatory cytokines in patients with chronic obstructive pulmonary disease.

BACKGROUND: Cadmium is a ubiquitous toxic heavy metal and environmental toxicant. Inflammation exerts central roles in the process of chronic obstructive pulmonary disease (COPD). However, few epidemiological studies on the correlation between cadmium exposure and COPD are available. The aim of this study was to evaluate the correlations among serum cadmium, inflammatory cytokines and pulmonary function in COPD patients. METHODS: All 940 COPD patients were finally recruited in this study. Demographic characteristics and clinical information were extracted. Fasting serum was collected. Serum cadmium was detected through graphite furnace atomic absorption spectrophotometry. Serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. RESULTS: All patients were classified into three groups according to the tertile division of serum cadmium concentration: low (<0.77 µg/L, L), medium (0.77-1.01 µg/L, M), and high (1.01 µg/L, H). Logistic regression analysis found that serum cadmium was inversely correlated with pulmonary function before and after adjusted confounding variables. When stratified by gender, serum cadmium was still negatively correlated with pulmonary function in COPD patients. Moreover, higher serum cadmium elevated CAT (COPD Assessment Test) score before and after adjusted confounding variables. Though a non-linear association between serum cadmium and inflammatory cytokines, serum cadmium was positively associated with inflammatory cytokines (TNF-α and MCP-1). TNF-α and MCP-1 exerted a partial mediator in the association between cadmium exposure and pulmonary function decline in COPD patients. CONCLUSIONS: Serum cadmium concentration is inversely correlated with pulmonary function among COPD patients. Inflammatory cytokines may be important mediators for cadmium-induced pulmonary function decline in COPD patients.

Sleep quality and mental health status of healthcare professionals during the outbreak of coronavirus disease 2019 (COVID-19).

To investigate the sleep quality and mental health status of healthcare professionals during the outbreak of coronavirus disease 2019 (COVID-19) in order to promote timely intervention and treatment. An Questionnaire Star of WeChat online survey was conducted at Hwamei Hospital, University of Chinese Academy of Sciences, NingBo, China. The questionnaire consisted of two parts including sociodemographic characteristics, and the Pittsburgh Sleep Quality Index (PSQI), the Generalized Anxiety Disorder (GAD-7) scale, a depression screening scale (Patient Health Questionnaire-9 [PHQ-9]) so as to investigate the sleep quality and mental health status of healthcare professionals during the outbreak of COVID-19.The data were analyzed with the t-test, χ2 test, one-way analysis of variance (ANOVA) and Pearson correlation, P < 0.05 was considered statistically significant. The mean score of PSQI is 5.8 ± 3.7 and the incidence of sleep disorders was 28.8% among the healthcare professionals and was related to occupation, title, education level, role and some underlying diseases. The positive rates for anxiety and depression among the healthcare professionals were 33.2% and 39.4% according to the GAD-7 and PHQ-9. Mental health status was related to occupation, education level, role and some underlying diseases. During the COVID-19 outbreak, sleep quality was significantly correlated with anxiety and depression among the healthcare professionals. The incidences of sleep disorder, anxiety and depression among healthcare professionals have been high. Furthermore, these disorders are interrelated and require timely intervention and treatment.

Stage-specific influence of temperature on the growth rate of Japanese Spanish mackerel (Scomberomorus niphonius) in early life.

Since 1850, each successive decade has been warmer than any preceding one. Warming could make a major contribution to the growth of fish larvae. To evaluate the influence of water temperature on the growth of larvae who spawned in later spring and early summer, we selected Scomberomorus niphonius, which has important ecological and economic value as a sample fish species. We conducted high-resolution spatiotemporal surveys during the 2015 spawning season at an important spawning ground in China. We found that the temperature required for larval survival was stricter than that for spawning. Within the appropriate temperature range, a rapid rise in water temperature was favourable for larval hatching, but S. niphonius hatched at relatively low temperature exhibited a faster growth rate in the yolk-sac and pre-flexion stages. The accumulated temperature and hatching temperature significantly affected the growth rate of S. niphonius larvae. The model that considered developmental stages provided a better explanation of the data than the model that only considered the temperature effect. The model improvement in terms of variance explained was higher for the early developmental stages than for the later developmental stages, suggesting that stage-specific temperature influences were prominent in the earlier stages, like the yolk-sac stage, and then reduced. Our results implied that water temperature anomalies could be hazardous to fish larvae, especially for fish spawning in late spring and early summer. Given that early-life stage fish are highly sensitive to water temperature, it is imperative to incorporate the potential effects of climate change into fisheries management.

Randomized, Double-Blinded, Placebo-Controlled Phase 2 Trial of an Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in Healthy Adults.

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.

Phosphorene Supported Single-Atom Catalysts for CO Oxidation: A Computational Study.

Single-atom catalysts (SACs) have attracted extensive attention owing to their high catalytic activity. The development of efficient SACs is crucial for applications in heterogeneous catalysis. In this article, the geometric configuration, electronic structure, stabilitiy and catalytic performance of phosphorene (Pn) supported single metal atoms (M=Ru, Rh, Pd, Ir, Pt, and Au) have been systematically investigated using density functional theory calculations and ab initio molecular dynamics simulations. The single atoms are found to occupy the hollow site of phosphorene. Among the catalysts studied, Ru-decorated phosphorene is determined to be a potential catalyst by evaluating adsorption energies of gaseous molecules. Various mechanisms including the Eley-Rideal (ER), Langmuir-Hinshelwood (LH) and trimolecular Eley-Rideal (TER) mechanisms are considered to validate the most favourable reaction pathway. Our results reveal that Ru-Pn exhibits outstanding catalytic activity toward CO oxidation reaction via TER mechanism with the corresponding rate-determining energy barrier of 0.44 eV, making it a very promising SAC for CO oxidation under mild conditions. Overall, this work may provide a new avenue for the design and fabrication of two-dimensional materials supported SACs for low-temperature CO oxidation.

Two insulin receptors determine alternative wing morphs in planthoppers.

Wing polyphenism is an evolutionarily successful feature found in a wide range of insects. Long-winged morphs can fly, which allows them to escape adverse habitats and track changing resources, whereas short-winged morphs are flightless, but usually possess higher fecundity than the winged morphs. Studies on aphids, crickets and planthoppers have revealed that alternative wing morphs develop in response to various environmental cues, and that the response to these cues may be mediated by developmental hormones, although research in this area has yielded equivocal and conflicting results about exactly which hormones are involved. As it stands, the molecular mechanism underlying wing morph determination in insects has remained elusive. Here we show that two insulin receptors in the migratory brown planthopper Nilaparvata lugens, InR1 and InR2, have opposing roles in controlling long wing versus short wing development by regulating the activity of the forkhead transcription factor Foxo. InR1, acting via the phosphatidylinositol-3-OH kinase (PI(3)K)-protein kinase B (Akt) signalling cascade, leads to the long-winged morph if active and the short-winged morph if inactive. InR2, by contrast, functions as a negative regulator of the InR1-PI(3)K-Akt pathway: suppression of InR2 results in development of the long-winged morph. The brain-secreted ligand Ilp3 triggers development of long-winged morphs. Our findings provide the first evidence of a molecular basis for the regulation of wing polyphenism in insects, and they are also the first demonstration--to our knowledge--of binary control over alternative developmental outcomes, and thus deepen our understanding of the development and evolution of phenotypic plasticity.