A Thermostable mRNA Vaccine against COVID-19.

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.

Revealing the pathogenesis of gastric intestinal metaplasia based on the mucosoid air-liquid interface.

BACKGROUND: Gastric intestinal metaplasia (GIM) is an essential precancerous lesion. Although the reversal of GIM is challenging, it potentially brings a state-to-art strategy for gastric cancer therapeutics (GC). The lack of the appropriate in vitro model limits studies of GIM pathogenesis, which is the issue this work aims to address for further studies. METHOD: The air-liquid interface (ALI) model was adopted for the long-term culture of GIM cells in the present work. This study conducted Immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), transcriptomic sequencing, and mucoproteomic sequencing (MS) techniques to identify the pathways for differential expressed genes (DEGs) enrichment among different groups, furthermore, to verify novel biomarkers of GIM cells. RESULT: Our study suggests that GIM-ALI model is analog to the innate GIM cells, which thus can be used for mucus collection and drug screening. We found genes MUC17, CDA, TRIM15, TBX3, FLVCR2, ONECUT2, ACY3, NMUR2, and MAL2 were highly expressed in GIM cells, while GLDN, SLC5A5, MAL, and MALAT1 showed down-regulated, which can be used as potential biomarkers for GIM cells. In parallel, these genes that highly expressed in GIM samples were mainly involved in cancer-related pathways, such as the MAPK signal pathway and oxidative phosphorylation signal pathway. CONCLUSION: The ALI model is validated for the first time for the in vitro study of GIM. GIM-ALI model is a novel in vitro model that can mimic the tissue micro-environment in GIM patients and further provide an avenue for studying the characteristics of GIM mucus. Our study identified new markers of GIM as well as pathways associated with GIM, which provides outstanding insight for exploring GIM pathogenesis and potentially other related conditions.

Targeted inhibition of the HNF1A/SHH axis by triptolide overcomes paclitaxel resistance in non-small cell lung cancer.

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.

Comparison of Lower and Upper Extremity Arteriovenous Graft: A Retrospective Clinical Analysis with 5-Year Follow-Up.

BACKGROUND: For patients in whom an upper extremity (UE) vascular access cannot be established, the lower extremity (LE) arteriovenous graft (AVG) could be selected. However, the application of LE AVG is limited owing to its high infection rate, uncertain patency time, and technical difficulties. This study aimed to compare the long-term patency rates and the incidence of vascular access complications of AVG in the LE and UE to provide a reference for the applications of AVG, especially in the LEs. METHODS: This was a retrospective analysis of patients who successfully underwent LE or UE AVG placement from March 2016 to October 2021. Patient characteristics were collected and compared using parameter or nonparameter tests according to data type. Postoperative patency was evaluated using Kaplan-Meier test. Postoperative complication incidence density and intergroup comparison were estimated using the Poisson distribution. RESULTS: Twenty-two patients with LE AVG and 120 patients with UE AVG were included. The 1-year primary patency rate was 67.4% (±11.0% standard error [SE]) in the LE group and 30.1% (±4.5% SE) in the UE group (P = 0.031). The assisted primary patency rate at postoperative months 12, 24, and 36 was respectively 78.6% (±9.6% SE), 65.5% (±14.4% SE), and 49.1% (±17.8% SE) in the LE group and 63.3% (±4.6% SE), 47.5% (±5.4% SE), and 30.4% (±6.1% SE) in the UE group (P = 0.137). The secondary patency rate at postoperative months 12, 24, and 36 remains 95.5% (±4.4% SE) in the LE group and 89.3% (±2.9% SE), 83.7% (±3.9% SE), and 73.0% (±6.2% SE), respectively, in the UE group (P = 0.200). Postoperative complications included stenosis, occlusion/thrombosis, infection, steal syndrome, pseudoaneurysm, severe postoperative serum swelling, and AVG exposure. The total incidence rates of postoperative complications were 0.87 (95% confidence interval [CI] 0.59-1.23) versus 1.61 (95% CI 1.45-1.79) (P = 0.001) cases/person-year, the incidence rates of stenosis were 0.45 (95% CI 0.26-0.73) versus 0.92 (95% CI 0.80-1.06) (P = 0.005) cases/person-year and the incidence rates of occlusion/thrombosis were 0.34 (95% CI 0.17-0.59) versus 0.62 (95% CI 0.52-0.74) cases/person-year in the LE group compared to those in the UE group (P = 0.041). CONCLUSIONS: LE AVG had higher primary patency rate and lower postoperative complication incidence than UE AVG. With the development of interventional technology, both LE AVG and UE AVG exhibited high secondary patency rates. LE AVG can be a reliable and long-term alternative for appropriately selected patients with unusable UE vessels.

Extension of a biotic ligand model for predicting the toxicity of neodymium to wheat: The effects of pH, Ca2+ and Mg2.

The damage excessive neodymium (Nd) causes to animals and plants should not be underestimated. However, there is little research on the impact of pH and associated ions on the toxicity of Nd. Here, a biotic ligand model (BLM) was expanded to predict the effects of pH and chief anions on the toxic impact of Nd on wheat root elongation in a simulated soil solution. The results suggested that Nd3+ and NdOH2+ were the major ions causing phytotoxicity to wheat roots at pH values of 4.5-7.0. The Nd toxicity decreased as the activities of H+, Ca2+, and Mg2+ increased but not when the activities of K+ and Na+ increased. The results indicated that H+, Ca2+, and Mg2+ competed with Nd for binding sites. An extended BLM was developed to consider the effects of pH, H+, Ca2+, and Mg2+, and the following stability constants were obtained: logKNdBL = 2.51, logKNdOHBL = 3.90, logKHBL = 4.01, logKCaBL = 2.43, and logKMgBL = 2.70. The results demonstrated that the BLM could predict the Nd toxicity well while considering the competition of H+, Ca2+, Mg2+ and the toxic species Nd3+ and NdOH2+ for binding sites.

Circular RNA circ-FIRRE interacts with HNRNPC to promote esophageal squamous cell carcinoma progression by stabilizing GLI2 mRNA.

Increasing evidence has shown that circular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) and promote cancer progression. However, the function and mechanism of the circRNA/RBP complex in esophageal squamous cell carcinoma (ESCC) are still largely unknown. Herein, we first characterized a novel oncogenic circRNA, circ-FIRRE, by RNA sequencing (Ribo-free) profiling of ESCC samples. Furthermore, we observed marked circ-FIRRE overexpression in ESCC patients with high TNM stage and poor overall survival. Mechanistic studies indicated that circ-FIRRE, as a platform, interacts with the heterogeneous nuclear ribonucleoprotein C (HNRNPC) protein to stabilize GLI2 mRNA by directly binding to its 3'-UTR in the cytoplasm, thereby resulting in elevated GLI2 protein expression and subsequent transcription of its target genes MYC, CCNE1, and CCNE2, ultimately contributing to ESCC progression. Moreover, HNRNPC overexpression in circ-FIRRE knockdown cells notably abolished circ-FIRRE knockdown-mediated Hedgehog pathway inhibition and ESCC progression impairment in vitro and in vivo. Clinical specimen results showed that circ-FIRRE and HNRNPC expression was positively correlated with GLI2 expression, which reveals the clear significance of the circ-FIRRE/HNRNPC-GLI2 axis in ESCC. In summary, our results indicate that circ-FIRRE could serve as a valuable biomarker and potential therapeutic target for ESCC and highlight a novel mechanism of the circ-FIRRE/HNRNPC complex in ESCC progression regulation.

Development of novel palbociclib-based CDK4/6 inhibitors exploring the back pocket behind the gatekeeper.

CDK4/6 inhibitors plus endocrine therapy is a standard therapy for HR+/HER2- breast cancer. Herein, using structure-based drug design strategy, a novel series of palbociclib derivatives were designed and synthesized as CDK4/6 inhibitors, among which compound 17m exhibited more potent CDK4/6 inhibitory activity and in vitro antiproliferative activity against the phosphorylated Rb-positive cell line MDA-MB-453 than the approved drug palbociclib. Moreover, compound 17m possessed remarkable CDK4/6 selectivity over other CDK family members including CDK1, CDK2, CDK3, CDK5, CDK7 and CDK9. The potent and selective CDK4/6 inhibitory activity endowed compound 17m with robust G1 cell cycle arrest ability in MDA-MB-453 cells. The intracellular inhibition of CDK4/6 by 17m was confirmed by western blot analysis of the levels of phosphorylated Rb in MDA-MB-453 cells. With respect to the metabolic stability, compound 17m possessed longer half-life (t1/2) in mouse liver microsome than palbociclib.

High-transmission and large group delay terahertz triple-band electromagnetically induced transparency in a metal-perovskite hybrid metasurface.

A high-transmission and large group delay terahertz triple-band electromagnetically induced transparency (EIT) effect is obtained in a metal-perovskite hybrid metasurface, which consists of a cross metal (CM), a pair of square metal frames (SMFs), and a pair of square split rings (SSRs). The results reveal that the transmission amplitudes of three transparent windows are 0.83, 0.9, and 0.89. The maximum values of group delays at three transparent windows are 7.64 ps, 4.07 ps, and 4.27 ps. The multipole scattering theory shows that the first and third transparent windows are created by the coupling between the electric dipole and toroidal dipole, and the second transparent window is created by the electric dipoles. The triple-band EIT effect can be dynamically controlled by adjusting the conductivity of perovskite while the modulation depths are 49.4%, 41%, and 31.5%. Moreover, the slow light effect can also be tunable by tuning the conductivity of perovskite while the modulation depths are 87.8%, 65.6%, and 68.4%. Our study puts forward a novel design concept for multi-band EIT effect and shows great prospects in the application of multi-band devices.

Polarization-insensitive electromagnetically induced transparency and its sensing performance based on spoof localized surface plasmons in vanadium dioxide-based terahertz metasurfaces.

The multi-layer terahertz metasurfaces are designed to achieve polarization-insensitive electromagnetically induced transparency (EIT) effect and its sensing performance based on spoof localized surface plasmons (S-LSPs). The unit cell of the proposed metasurfaces is comprised of a metallic spiral (MS) structure, square metal frame (SMF) structure, and vanadium dioxide (VO2) layer. The EIT effect is realized by the bright-bright coupling between spoof electric localized surface plasmons (S-ELSPs) and electric dipole, which can be proved by the multipole scattering theory. The maximum value of transmission amplitude at the transparent window is 0.91, and the modulation depth can reach 51% by adjusting the conductivity of VO2. The theoretical results based on the two-particle model show excellent agreement with the simulated results. Moreover, the change of polarization angle has little effect on the EIT effect and the proposed metasurfaces show polarization-insensitive characteristics. The slow light effect of the proposed metasurfaces can also be dynamically controlled by tuning the conductivity of VO2. Due to the high Q value of the transparent window, the proposed metasurfaces exhibit excellent sensing performance, and the sensitivity is 0.172 THz RIU-1. Our study provides a method for the fabrication of EIT metasurfaces and has a broad application prospect in slow light devices, sensors, and modulators.

Tunable and three-dimensional dual-band metamaterial absorber based on electromagnetically induced transparency with vanadium dioxide.

A tunable and three-dimensional dual-band metamaterial absorber based on electromagnetically induced transparency (EIT) is proposed. The unit cell of the metamaterial absorber consisted of a cut wire (CW), two split ring resonators (SRRs), a metal plate and a patterned vanadium dioxide (VO2) film. The two absorption peaks could be dynamically controlled by tuning the conductivity of VO2 with the maximum absorptions of 97.5% at 1.05 THz and 96.5% at 1.16 THz. The physical mechanism of the metamaterial absorber was explained by the electric field, magnetic field, power loss density and surface current distributions. In addition, the metamaterial absorber exhibited a wide polarization angle for y-polarization wave and x-polarization wave and showed good robustness against oblique incidence. Moreover, the metamaterial absorber exhibited a high fault tolerance with a variation in the geometric parameters. Our work provides a novel method for the fabrication of multi-band metamaterial absorbers and has promising applications in terahertz sensors, modulators and filters.

Efficient optimization and development of two methods for the determination of acrylamide in deep-frying oil by liquid chromatography-tandem mass spectrometry: Application of multifactor analysis assessment strategy.

A new multifactor analysis assessment strategy was developed for evaluating, optimizing, and comparing analytical techniques for acrylamide in frying oils. Based on five indices (absolute recovery, absolute matrix effect, the intensity of the full ion scan, and the precursor ion scan to m/z 184 and m/z 241), the proposed strategy was performed with radar analysis, relative contribution analysis, and the entropy-weighted technique for order performance by similarity to ideal solution analysis. Two novel methods based on quick, easy, cheap, effective, rugged, and safe extraction methodology and gel permeation chromatography-liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry have been developed for the analysis of acrylamide in frying oils. Two methods were suitable for rapid and sensitive analysis of acrylamide in oils in different laboratories, with a limit of quantitation at 2 µg/kg, and the average recovery ranging from 92.5% to 107.8%, with relative standard deviations below 10%. When considering automation efficiency and matrix effects, gel permeation chromatography is the most efficient method, whereas the other method has an advantage when analyzing large samples. The developed methods were used in a pilot study to analyze frying oils with acrylamide content below 9.82 µg/kg, showing that the repeated frying process did not produce significant content of acrylamide in oils.

Optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage for transfer in women 38 years and older.

PURPOSE: We aimed to evaluate the pregnancy outcomes of cleavage-stage embryo transfers (ETs) for the first time and explore optimal number of high-quality cleavage-stage embryos for extended culture to blastocyst-stage in women of advanced maternal age (AMA). METHODS: We retrospectively identified 1646 AMA women ≥ age 38 years for the first fresh ETs between January 2014 and December 2020 at our hospital. Double ETs were divided into three groups as follows: DET-HH (two high-quality embryos), DET-HL (one high-quality and one low-quality embryo), and DET-LL (two low-quality embryos) groups. We mainly analyzed the pregnancy outcomes of double cleavage-stage ETs with different embryo grades and blastocyst-stage ETs with different number of high-quality cleavage-stage embryos on day 3. RESULTS: Our data indicated that the DET-HH group had significantly higher clinical pregnancy, ongoing pregnancy, and live birth rates than DET-HL and DET-LL groups (p < .05). For extended culture to blastocyst-stage with 2 (D3-2H), 3 (D3-3H), and 4 (D3-≥4H) high-quality cleavage-stage embryos, the D3-≥ 4H group had significantly higher ongoing pregnancy and live birth rates than D3-2H and D3-3H groups (p < .05). We observed that the number of high-quality embryos on day 3 was independently associated with live birth rate for blastocyst transfers (OR: 1.133, 95% CI 1.023-1.256, p = .017). There were no significant differences in the clinical pregnancy, ongoing pregnancy and live birth rates among DET-HH, D3-2H and D3-3H groups (p > .05). CONCLUSIONS: Extended culture to blastocyst-stage for transfer was safe and recommended for AMA women with ≥ 4 high-quality embryos on day 3.

Precision Structural Interpretation of Site-Specific N-Glycans in Seminal Plasma.

N-Linked glycoproteins are rich in seminal plasma, playing various essential roles in supporting sperm function and the fertilization process. However, the detailed information on these glycoproteins, particularly site-specific glycan structures, is still limited. In this study, a precision site-specific N-glycoproteome map of human seminal plasma was established by employing the site-specific glycoproteomic approach and a recently developed glycan structure interpretation software, StrucGP. A total of 9567 unique glycopeptides identified in human seminal plasma were composed of 773 N-linked glycan structures and 1019 N-glycosites from 620 glycoproteins. These glycans were comprised of four types of core structures and 13 branch structures. The majority of identified glycoproteins functioned in response to stimulus and immunity. As we reported in human spermatozoa, heavy fucosylation (fucose residues ≥6 per glycan) was also detected on seminal plasma glycoproteins such as clusterin and galectin-3-binding protein, which were involved in the immune response of biological processes and reactome pathways. Comparison of site-specific glycans between seminal plasma and spermatozoa revealed more complicated glycan structures in seminal plasma than in spermatozoa, even on their shared glycoproteins. These present data will be greatly beneficial for the in-depth structural and functional study of glycosylation in the male reproduction system.

Screening of phosphate-solubilizing bacteria and their abilities of phosphorus solubilization and wheat growth promotion.

BACKGROUND: Phosphate-solubilizing bacteria (PSB) can enhance plant growth and phosphorus (P) solubilization, it also has been reported to reduce the negative effects of overused agricultural fertilizer in farmland and protect the soil environment. However, the mechanism behind this interaction has not been fully elucidated. RESULTS: In this study, we screened out Pseudomonas moraviensis, Bacillus safensis, and Falsibacillus pallidus which can both solubilize P efficiently and produce indole-3-acetic acid (IAA) from sandy fluvo-aquic soils. The yield of wheat (Triticum aestivum) under PSB inoculation significantly increased up to 14.42% (P < 0.05) compared with the control treatment in phosphate fertilizer-used farmland. Besides promoting wheat growth, we found the labile P fraction in soil was significantly increased by over 122.04% (P < 0.05) under PSB inoculation compared with it in soils without, in parallel, the stable P fraction was significantly reduced by over 46.89% (P < 0.05). Furthermore, PSB inoculation increased the soil microbial biomass and activity, indicating that PSB screened out in this work performed a remarkable ability to colonize the soils in the wheat field. CONCLUSION: PSB from sandy fluvo-aquic soil improve wheat growth and crop productivity by increasing the labile P fraction and IAA content in the greenhouse and wheat field. Our work provides an environment and economy-friendly bacterial resource that potentially promotes sustainable agricultural development in the long term.

Design, synthesis and biological evaluation of dual HDAC and VEGFR inhibitors as multitargeted anticancer agents.

Herein, a novel series of dual histone deacetylase (HDAC) and vascular endothelial growth factor receptor (VEGFR) inhibitors were designed, synthesized and biologically evaluated based on previously reported pazopanib-based HDAC and VEGFR dual inhibitors. Most target compounds showed significant HDAC1, HDAC6 and VEGFR2 inhibition, which contributed to their potent antiproliferative activities against multiple cancer cell lines and significant antiangiogenic potencies in both human umbilical vein endothelial cell (HUVEC) tube formation assays and rat thoracic aorta ring assays. Further HDAC selectivity evaluations indicated that hydroxamic acids 5 and 9e possessed HDAC isoform selectivity profiles similar to that of the approved HDAC inhibitor suberoylanilide hydroxamic acid(SAHA), while hydrazide12 presented an HDAC isoform selectivity profilesimilar to that of the clinical HDAC inhibitor MS-275. The VEGFR inhibition profiles of 5, 9e and 12 were similar to that of the approved VEGFR inhibitor pazopanib. The intracellular target engagements of Compounds 5 and 12 were confirmed by western blot analysis. The metabolic stabilities of 5, 9e and 12 in mouse liver microsomes were inferior to that of pazopanib. These dual HDAC and VEGFR inhibitors provide lead compounds for further structural optimization to obtainpolypharmacological anticancer agents.

Bi-allelic mutations in MOS cause female infertility characterized by preimplantation embryonic arrest.

STUDY QUESTION: Are mutations in MOS (MOS proto-oncogene, serine/threonine kinase) involved in early embryonic arrest in infertile women? SUMMARY ANSWER: We identified mutations in MOS that may cause human female infertility characterized by preimplantation embryonic arrest (PREMBA), and the effects of the mutations in human embryonic kidney 293T (HEK293T cells) and mouse oocytes provided evidence for a causal relation between MOS and female infertility. WHAT IS KNOWN ALREADY: MOS, an activator of mitogen-activated protein kinase, mediates germinal vesicle breakdown and metaphase II arrest. Female MOS knockout mice are viable but sterile. Thus, MOS seems to be an important part of the mammalian cell cycle mechanism that regulates female meiosis. STUDY DESIGN, SIZE, DURATION: Whole-exome sequencing, bioinformatics filtering analysis and genetic analysis were performed to identify two different biallelic mutations in MOS in two independent families. The infertile patients presenting with early embryonic arrest were recruited from October 2018 to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: The female patients diagnosed with primary infertility were recruited from the reproduction centres of local hospitals. Genomic DNA from the affected individuals, their family members and healthy controls was extracted from peripheral blood. We performed whole-exome sequencing in patients diagnosed with PREMBA. Functional effects of the mutations were investigated in HEK293T cells by western blotting and in mouse oocytes by microinjection and immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE: We identified the homozygous missense mutation c.285C>A (p.(Asn95Lys)) and the compound heterozygous mutations c.467delG (p.(Gly156Alafs*18)) and c.956G>A (p.(Arg319His)) in MOS in two independent patients. The mutations c.285C>A (p.(Asn95Lys)) and c.467delG (p.(Gly156Alafs*18)) reduced the protein level of MOS, and all mutations reduced the ability of MOS to phosphorylate its downstream target, extracellular signal-regulated kinase1/2. In addition, the identified mutations reduced the capacity of exogenous human MOS to rescue the metaphase II exit phenotype, and the F-actin cytoskeleton of mouse oocytes was affected by the patient-derived mutations. LIMITATIONS, REASONS FOR CAUTION: Owing to the lack of in vivo data from patient oocytes, the exact molecular mechanism affected by MOS mutations and leading to PREMBA is still unknown and should be further investigated using knock-out or knock-in mice. WIDER IMPLICATIONS OF THE FINDINGS: We identified recessive mutations in MOS in two independent patients with the PREMBA phenotype. Our findings reveal the important role of MOS during human oocyte meiosis and embryonic development and suggest that mutations in MOS may be precise diagnostic markers for clinical genetic counselling. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81725006, 81822019, 81771581, 81971450, 81971382,82001538 and 82071642), the project supported by the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), the Project of the Shanghai Municipal Science and Technology Commission (19JC1411001), the Natural Science Foundation of Shanghai (19ZR1444500 and 21ZR1404800), the Shuguang Program of the Shanghai Education Development Foundation and the Shanghai Municipal Education Commission (18SG03), the Foundation of the Shanghai Health and Family Planning Commission (20154Y0162), the Capacity Building Planning Program for Shanghai Women and Children's Health Service and the collaborative innovation centre project construction for Shanghai Women and Children's Health. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Development and perspectives of rapid detection technology in food and environment.

Food safety become a hot issue currently with globalization of food trade and food supply chains. Chemical pollution, microbial contamination and adulteration in food have attracted more attention worldwide. Contamination with antibiotics, estrogens and heavy metals in water environment and soil environment have also turn into an enormous threat to food safety. Traditional small-scale, long-term detection technologies have been unable to meet the current needs. In the monitoring process, rapid, convenient, accurate analysis and detection technologies have become the future development trend. We critically synthesizing the current knowledge of various rapid detection technology, and briefly touched upon the problem which still exist in research process. The review showed that the application of novel materials promotes the development of rapid detection technology, high-throughput and portability would be popular study directions in the future. Of course, the ultimate aim of the research is how to industrialization these technologies and apply to the market.

Can a molecular switch exist in both superalkali electride and superalkalide forms?

To combine both electride and alkalide characteristics in one molecular switch, it is shown herein that the phenalenyl radical and the M3 ring (M3-PHY, M = Li, Na, and K) stacked with parallel and vertical geometries are good candidates. The former geometry is the superalkali electride e-⋯M3+-PHY while the latter geometry is the superalkalide Mδ--M2(1-δ)+-PHY-. The superalkalide Mδ--M2(1-δ)+-PHY- may isomerize to the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K) using suitable long-wavelength irradiation, while the latter may isomerize to the former with suitable short-wavelength irradiation. Also, applying suitable oriented external electric fields can drive the superalkalide Mδ-M2(1-δ)+-PHY- to change into the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K). The differences in the static and dynamic first hyperpolarizability (ß0) values between them were also studied.

Isoquinoline Alkaloids as Protein Tyrosine Phosphatase Inhibitors from a Deep-Sea-Derived Fungus Aspergillus puniceus.

Puniceusines A-N (1-14), 14 new isoquinoline alkaloids, were isolated from the extracts of a deep-sea-derived fungus, Aspergillus puniceus SCSIO z021. Their structures were elucidated by spectroscopic analyses. The absolute configuration of 9 was determined by ECD calculations, and the structures of 6 and 12 were further confirmed by a single-crystal X-ray diffraction analysis. Compounds 3-5 and 8-13 unprecedentedly contained an isoquinolinyl, a polysubstituted benzyl or a pyronyl at position C-7 of isoquinoline nucleus. Compounds 3 and 4 showed selective inhibitory activity against protein tyrosine phosphatase CD45 with IC50 values of 8.4 and 5.6 µM, respectively, 4 also had a moderate cytotoxicity towards human lung adenocarcinoma cell line H1975 with an IC50 value of 11.0 µM, and 14, which contained an active center, -C=N+, exhibited antibacterial activity. An analysis of the relationship between the structures, enzyme inhibitory activity and cytotoxicity of 1-14 revealed that the substituents at C-7 of the isoquinoline nucleus could greatly affect their bioactivity.

A Draft Mitogenome of Plectus Murrayi.

Plectus murrayi is a free-living microbivorous nematode endemic to Antarctic soils. Our draft assembly of its mitogenome was 15,656 bp long, containing 12 protein-coding, eight transfer RNA (tRNA), and two ribosomal RNA (rRNA) genes. Mitophylogenomic analyses extend our understanding of mitochondrial evolution in Nematoda.