Characterization of CCoV-HuPn-2018 spike protein-mediated viral entry.

Canine coronavirus-human pneumonia-2018 (CCoV-HuPn-2018) was recently isolated from a child with pneumonia. This novel human pathogen resulted from cross-species transmission of a canine coronavirus. It has been known that CCoV-HuPn-2018 uses aminopeptidase N (APN) from canines, felines, and porcines, but not humans, as functional receptors for cell entry. The molecular mechanism of cell entry in CCoV-HuPn-2018 remains poorly understood. In this study, we demonstrated that among the nine APN orthologs tested, the APN of the Mexican free-tailed bat could also efficiently support CCoV-HuPn-2018 spike (S) protein-mediated entry, raising the possibility that bats may also be an alternative host epidemiologically important for the transmission of this virus. The glycosylation at residue N747 of canine APN is critical for its receptor activity. The gain of glycosylation at the corresponding residues in human and rabbit APNs converted them to functional receptors for CCoV-HuPn-2018. Interestingly, the CCoV-HuPn-2018 spike protein pseudotyped virus infected multiple human cancer cell lines in a human APN-independent manner, whereas sialic acid appeared to facilitate the entry of the pseudotyped virus into human cancer cells. Moreover, while host cell surface proteases trypsin and TMPRSS2 did not promote the entry of CCoV-HuPn-2018, endosomal proteases cathepsin L and B are required for the entry of CCoV-HuPn-2018 in a pH-dependent manner. IFITMs and LY6E are host restriction factors for the CCoV-HuPn-2018 entry. Our results thus suggest that CCoV-HuPn-2018 has not yet evolved to be an efficient human pathogen. Collectively, this study helps us understand the cell tropism, receptor usage, cross-species transmission, natural reservoir, and pathogenesis of this potential human coronavirus. IMPORTANCE Viral entry is driven by the interaction between the viral spike protein and its specific cellular receptor, which determines cell tropism and host range and is the major constraint to interspecies transmission of coronaviruses. Aminopeptidase N (APN; also called CD13) is a cellular receptor for HCoV-229E, the newly discovered canine coronavirus-human pneumonia-2018 (CCoV-HuPn-2018), and many other animal alphacoronaviruses. We examined the receptor activity of nine APN orthologs and found that CCoV-HuPn-2018 utilizes APN from a broad range of animal species, including bats but not humans, to enter host cells. To our surprise, we found that CCoV-HuPn-2018 spike protein pseudotyped viral particles successfully infected multiple human hepatoma-derived cell lines and a lung cancer cell line, which is independent of the expression of human APN. Our findings thus provide mechanistic insight into the natural hosts and interspecies transmission of CCoV-HuPn-2018-like coronaviruses.

Design, synthesis and bioactivity evaluation of novel monomethyl auristatin F analogues.

Monomethyl auristatin F (MMAF), a synthetic analogue of the natural compound dolastatin 10, has garnered significant attention in cancer research due to its high potency in vitro. While previous studies have focused on modifying the N-terminal extension of the amino group and the C-terminal modification of the carboxyl group, there has been limited exploration into modifying the P1 and P5 side chains. In this study, we substituted the valine residue at the P1 position with various natural or unnatural amino acids and introduced triazole functional groups at the P5 side chain. Compounds 11k and 18d exhibited excellent inhibition on tubulin. Additionally, compound 18d demonstrated enhanced cytotoxicity against HCT116 cells compared to the parent compound MMAF, suggesting its potential as a cytotoxic payload for further antibody-drug conjugates (ADCs) development.

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines.

Herein, we report a visible-light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester alkylpalladium radical with the release of dinitrogen. The radical intermediate selectively adds to the double bond of a 1,3-diene or allene, followed by the allylpalladium radical-polar crossover path and selective allylic substitution with the amine substrate, thereby leading to a single unsaturated γ- or ε-amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this multicomponent reaction protocol.

Reduced neutralization and Fc effector function to Omicron subvariants in sera from SARS-CoV-1 survivors after two doses of CoronaVac plus one dose subunit vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron harbors more than 30 mutations of the spike protein and exhibits substantial immune evasion. Although previous study indicated that BNT162b2 messenger RNA vaccine induces potent cross-clade pan-sarbecovirus neutralizing antibodies in survivors of the infection by SARS-CoV-1, the neutralization activity and Fc-mediated effector functions of these cross-reactive antibodies elicited in SARS-CoV-1 survivors to Omicron subvariants still remain largely unknown. In this study, the neutralization activity and Fc-mediated effector functions of antibodies boosted by a third dose vaccination were characterized in SARS-CoV-1 convalescents and healthy individuals. Potent cross-clade broadly neutralizing antibodies were observed in SARS-CoV-1 survivors who received a three-dose vaccination regimen consisting of two priming doses of CoronaVac followed by one booster dose of the protein subunit vaccine ZF2001. However, the induced antibodies exhibited both reduced neutralization and impaired Fc effector functions targeting multiple Omicron subvariants. Importantly, the data also support the notion that immune imprints resulted from SARS-CoV-1 infection may exacerbate the impairment of neutralization activity and Fc-mediated effector functions to Omicron subvariants and provided invaluable information to vaccination strategy in future.

EBSD patterns simulating multilayer twins based on dynamical theory of electron diffraction.

Electron backscatter diffraction (EBSD) can be employed to determine crystal structures but has not been used alone to identify defects at the atom scale due to the lack of understanding of the EBSD patterns generated by various structure defects. In the present work, the EBSD patterns of FCC-Fe with 9-layer, 6-layer and 3-layer twin structures are simulated, respectively, using the revised real space (RRS) method and compared with the counterpart of perfect crystals. Our results show that when the electron beam is incident along a direction parallel to the twin plane, the pattern appears symmetrical with respect to the corresponding Kikuchi band of the twin plane, and the diffraction details within the Kikuchi band also exhibit symmetry with respect to the middle line of the Kikuchi band. Moreover, the overall clarity of the patterns decreases, and the pattern becomes more blurred with increasing the distance from the Kikuchi band corresponding to the twin plane. By contrast, the incident electron beam along the direction perpendicular to the twin plane results in diffraction superposition of the matrix region and the shear region, which shows twofold rotational symmetry with respect to the Kikuchi pole corresponding to the normal to the twin plane. In addition, some extra Kikuchi bands appear in the EBSD patterns due to the long-period structures of the multilayer twins. As the number of multilayer twins decreases, the number of extra Kikuchi bands decreases and the area of the blurring pattern increases. The correlation between twin structures and EBSD patterns provides theoretical insights for identifying twin structures by the EBSD technique.

Evolution Law of Concrete Interface Stress of Rigid-Frame Arch under Construction and Its Impact on Ultimate Load-Bearing Capacity.

To study the evolution of stress on the ring and segment interfaces during the construction process of the concrete encapsulation of the main arch ring in a rigid-frame arch bridge, alongside its impact on the ultimate load-bearing capacity of the main arch ring, a 1:10 scale model experiment was conducted by taking the 600 m Tian'e Longtan Bridge as the prototype. The key cross-section concrete strain data were collected during the entire construction process of the main arch ring via fiber-optic strain sensors, which were used to investigate the stress evolution at ring and segment interfaces. ANSYS APDL was employed to simulate the ultimate bearing capacity under various loading conditions of two different finite element models, which were, respectively, formed segmentally and by single pouring. The results revealed that (1) after the closure of the concrete encapsulation of the main arch ring, the concrete stress in the cross-section exhibits significant stress disparities. At the same cross-section, the level of the web concrete stress can reach 76% of the floor concrete stress, while the roof concrete stress level is less than 20% of the floor concrete stress. (2) At the junction of two adjacent work planes, there are considerable differences in the stress levels of the concrete on both sides. After the closure of the main arch ring, the intersegment stress ratios of the floor, web, and roof concrete are 60~70%, 40~60%, and 0~5%, respectively. (3) Loading conditions remarkably affected the ultimate bearing capacity of the main arch ring. Under mid-span loading and 1/4 span symmetrical loading conditions, compared to single-pour concrete encapsulation, the ultimate bearing capacity of the main arch ring with concrete encapsulated by segmented and ring-divided pouring decreased by 19.16% and 5.23%, respectively, compared to single-pour concrete encapsulation. This suggests that the non-uniformity of stress distribution in the concrete sheath can lead to reductions in the ultimate bearing capacity of the arch ring.

Loss-of-function Mutations K11E or E271K Lead to Novel Tumor Suppression, Implicate Nucleolar Helicase DDX24 Oncogenicity.

Purpose: Mutations (K11E or E271K) of DEAD-box RNA helicase 24 (DDX24) were related to multi-organ venous lymphatic malformation syndrome (MOVLD). However, the relationship between these mutations and DDX24-function still remains unknown. Understanding whether K11E and E271K cause "loss-of-function" or "gain-of-function" for DDX24 is significant for related diseases. DDX24 was reported to be related to tumors closely, thus this study aims to explore how K11E and E271K affect DDX24-function in tumor proliferation. Methods: Cell lines stably expressing wild-type DDX24, K11E-DDX24, E271K-DDX24, along with vector only based on Chinese hamster ovary cells (CHO) and Balb/c tumor-bearing mice models were constructed. Then immunofluorescence staining, proliferation assay and colony formation assay in vitro and 18F-FDG PET/CT-scan were performed. Finally, the tumor tissues were collected to perform transcriptome sequencing to predict the potential mechanism. Results: Contrasted with CHO-WT-DDX24, CHO-K11E-DDX24 or CHO-E271K-DDX24 showed a decreased number of nucleoli, a slower proliferation rate and a lower colony formation rate significantly. Moreover, mice, inoculated with CHO-K11E-DDX24 or CHO-E271K-DDX24 cells, showed lower tumor formation rate, slower tumor growth rate, better prognosis, reduced standard uptake value and Ki of glucose in subcutaneous tumors. Sequencing indicated CHO-K11E-DDX24 or CHO-E271K-DDX24 caused increasing expression of TNF or chemokines and alteration in immune-related signal pathways. Conclusion: K11E or E271K mutation could lead to "loss-of-function" of DDX24 in cell proliferation and tumor bearing mice, which may be acted by non-specific immune killing to inhibit tumor growth.

Bacteriocin production and inhibition of Bacillus subtilis by Lactobacillus paracasei HD1.7 in an indirect coculture system.

A broad-spectrum antimicrobial peptide named Paracin 1.7 was produced by Lactobacillus paracasei HD1.7, which was isolated from Chinese sauerkraut juice. In this study, the influence of cocultivation on the communication mechanism of L. paracasei HD1.7 and Bacillus subtilis was investigated. The two bacterial strains were grown in monoculture and indirect coculture, and the growth of both bacteria and bacteriocin production as well as the transcriptional level of luxS in L. paracasei HD1.7 and spo0A in B. subtilis were monitored. Bacteriocin production and cell numbers were increased significantly when L. paracasei HD1.7 cells were indirectly cocultured with B. subtilis, and bacteriocin-producing L. paracasei HD1.7 can prevent the growth and sporulation of B. subtilis. After indirect coculture with B. subtilis, the expression of luxS in L. paracasei HD1.7 increased in the exponential growth phase and decreased in the stationary phase compared to monoculture. The expression of spo0A in B. subtilis dropped in the indirect coculture compared to the monoculture. It indicate that the upregulation of luxS is due to a response to a secreted compound produced by B. subtilis. The results show L. paracasei HD1.7 has an amensalism on B. subtilis, while B. subtilis has a commensalism on L. paracasei HD1.7.

LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic SARS-CoV-2.

C3A is a subclone of the human hepatoblastoma HepG2 cell line with strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ArfGAP with dual pleckstrin homology (PH) domains 2 (ADAP2), gamma-interferon-inducible lysosome/endosome-localized thiolreductase (GILT), and lymphocyte antigen 6 family member E (LY6E), the three cellular proteins identified to function in interference with virus entry, were expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-O43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a mechanism distinct from other factors that modulate CoV entry.IMPORTANCE Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control of host innate and adaptive immune responses. In the last decade, several interferon-inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH, and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as a host factor that facilitates the entry of several human-pathogenic viruses, including human immunodeficiency virus, influenza A virus, and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.

Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2.

The COVID-19 pandemic has caused an unprecedented global public health and economic crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, unlike the SARS-CoV-2-like coronaviruses (CoVs) identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2.

Barriers and facilitators for cervical cancer screening among adolescents and young people: a systematic review.

BACKGROUND: Though cervical cancer is one of the leading causes of cancer-related death globally, its incidence is nearly entirely preventable. Young people have been an international priority for screening as this population has historically been under-screened. However, in both high-income and low-income countries, young people have not been screened appropriately according to country-specific guidelines. The aim of this systematic review was to systematically characterize the existing literature on barriers and facilitators for cervical cancer screening (CCS) among adolescents and young people globally. METHODS: We conducted a systematic review following PRISMA guidelines of three key databases: Medline-OVID, EMBASE, and CINAHL. Supplementary searches were done through ClinicialTrials.Gov and Scopus. Databases were examined from 1946 until the date of our literature searches on March 12th 2020. We only examined original, peer-reviewed literature. Articles were excluded if they did not specifically discuss CCS, were not specific to individuals under the age of 35, or did not report outcomes or evaluation. All screening, extraction, and synthesis was completed in duplicate with two independent reviewers. Outcomes were summarized descriptively. Risk of bias for individual studies was graded using an adapted rating scale based on the Risk of Bias Instrument for Cross-Sectional Surveys of Attitudes and Practices. RESULTS: Of the 2177 original database citations, we included 36 studies that met inclusion criteria. The 36 studies included a total of 14,362 participants, and around half (17/36, 47.2%) of studies specifically targeted students. The majority of studies (31/36, 86.1%) discussed barriers and facilitators to Pap testing specifically, while one study analyzed self-sampling (1/36, 2.8%), one study targeted HPV DNA testing (1/36, 2.8%), and the remainder (4/36, 11.1%) were not specified. Our systematic review found that there are three large categories of barriers for young people: lack of knowledge/awareness, negative perceptions of the test, and systemic barriers to testing. Facilitators included stronger relationships with healthcare providers, social norms, support from family, and self-efficacy. CONCLUSION: There are unique barriers and facilitators that affect CCS rates in adolescents and young people. Health systems and healthcare providers worldwide should address the challenges for this unique population.

Interventions to Prevent and Treat Burnout in Obstetrics/Gynaecology: A Scoping Review.

OBJECTIVE: Obstetricians and gynaecologists are among the highest risk specialties for burnout. There is growing evidence that physician burnout can be both prevented and reduced. We sought to characterize the evidence base for interventions related to the prevention and treatment of burnout in obstetrics and gynaecology DATA SOURCES: We conducted a scoping review following PRISMA guidelines of 5 databases: (Medline-OVID, EMBASE, CINAHL, ClinicalTrials.gov, and PsycInfo) from inception to March 17, 2020. Citations of relevant articles were hand-searched to maximize sensitivity. STUDY SELECTION: All interventional study designs were included. The target study population was obstetrics and gynaecology residents, learners, or staff. Published conference posters, papers, and abstracts were eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: All extraction and descriptive analysis was completed by two independent reviewers. Outcomes were summarized descriptively. Appraisal was completed using the Cochrane Risk of Bias tool and Risk of Bias Assessment tool for Non-randomized Studies. RESULTS: Of the 1540 original database citations, 20 studies met our inclusion criteria. A total of 589 obstetrics/gynaecology participants were included. While there was an overall a lack of research in the field, there were several promising interventions that target residents. There were a combination of preventative interventions (e.g. yoga, nutritional programs, or narrative medicine initiatives) as well as treatments (e.g. counselling appointments or debrief sessions). The vast majority of these interventions focused on individual-specific interventions rather than structural changes. In addition, the majority of interventions appeared to be "proof of concept" and feasability-related studies, with many studies published as conference abstracts rather than peer-reviewed journal publications. CONCLUSIONS: Institutions should continue to implement interventions that address burnout in obstetrics and gynaecology. Further research is required on long-term outcomes of interventions as well as structural strategies.

Maize WRKY Transcription Factor ZmWRKY79 Positively Regulates Drought Tolerance through Elevating ABA Biosynthesis.

Drought stress causes heavy damages to crop growth and productivity under global climatic changes. Transcription factors have been extensively studied in many crops to play important roles in plant growth and defense. However, there is a scarcity of studies regarding WRKY transcription factors regulating drought responses in maize crops. Previously, ZmWRKY79 was identified as the regulator of maize phytoalexin biosynthesis with inducible expression under different elicitation. Here, we elucidated the function of ZmWRKY79 in drought stress through regulating ABA biosynthesis. The overexpression of ZmWRKY79 in Arabidopsis improved the survival rate under drought stress, which was accompanied by more lateral roots, lower stomatal aperture, and water loss. ROS scavenging was also boosted by ZmWRKY79 to result in less H2O2 and MDA accumulation and increased antioxidant enzyme activities. Further analysis detected more ABA production in ZmWRKY79 overexpression lines under drought stress, which was consistent with up-regulated ABA biosynthetic gene expression by RNA-seq analysis. ZmWRKY79 was observed to target ZmAAO3 genes in maize protoplast through acting on the specific W-boxes of the corresponding gene promoters. Virus-induced gene silencing of ZmWRKY79 in maize resulted in compromised drought tolerance with more H2O2 accumulation and weaker root system architecture. Together, this study substantiates the role of ZmWRKY79 in the drought-tolerance mechanism through regulating ABA biosynthesis, suggesting its broad functions not only as the regulator in phytoalexin biosynthesis against pathogen infection but also playing the positive role in abiotic stress response, which provides a WRKY candidate gene to improve drought tolerance for maize and other crop plants.

Boronate Affinity Fluorescent Nanoparticles for Förster Resonance Energy Transfer Inhibition Assay of cis-Diol Biomolecules.

Förster resonance energy transfer (FRET) has been essential for many applications, in which an appropriate donor-acceptor pair is the key. Traditional dye-to-dye combinations remain the working horses but are rather nonspecifically susceptive to environmental factors (such as ionic strength, pH, oxygen, etc.). Besides, to obtain desired selectivity, functionalization of the donor or acceptor is essential but usually tedious. Herein, we present fluorescent poly(m-aminophenylboronic acid) nanoparticles (poly(mAPBA) NPs) synthesized via a simple procedure and demonstrate a FRET scheme with suppressed environmental effects for the selective sensing of cis-diol biomolecules. The NPs exhibited stable fluorescence properties, resistance to environmental factors, and a Förster distance comparable size, making them ideal donor for FRET applications. By using poly(mAPBA) NPs and adenosine 5'-monophosphate modified graphene oxide (AMP-GO) as a donor and an acceptor, respectively, an environmental effects-suppressed boronate affinity-mediated FRET system was established. The fluorescence of poly(mAPBA) NPs was quenched by AMP-GO while it was restored when a competing cis-diol compounds was present. The FRET system exhibited excellent selectivity and improved sensitivity toward cis-diol compounds. Quantitative inhibition assay of glucose in human serum was demonstrated. As many cis-diol compounds such as sugars and glycoproteins are biologically and clinically significant, the FRET scheme presented herein could find more promising applications.

Hybrid Approach Combining Boronate Affinity Magnetic Nanoparticles and Capillary Electrophoresis for Efficient Selection of Glycoprotein-Binding Aptamers.

Capillary electrophoresis (CE) and magnetic beads have been widely used for the selection of aptamers owing to their efficient separation ability. However, these methods alone are associated with some apparent drawbacks. CE suffers from small injection volumes and thereby only a limited amount of aptamer can be collected at each round. While the magnetic beads approach is often associated with tedious procedure and nonspecific binding. Herein we present a hybrid approach that combines the above two classical aptamer selection methods to overcome the drawbacks associated with these methods alone. In this hybrid method, one single round selection by boronate affinity magnetic nanoparticles (BA-MNPs) was first performed and then followed by a CE selection of a few rounds. The BA-MNPs-based selection eliminated nonbinding sequences, enriching effective sequences in the nucleic acid library. While the CE selection, which was carried out in free solutions, eliminated steric hindrance effects in subsequent selection. Two typical glycoproteins, Ribonuclease B (RNase B) and alkaline phosphatase (ALP), were used as targets. This hybrid method allowed for efficient selection of glycoprotein-binding aptamers within 4 rounds (1 round of BA-MNPs-based selection and 3 rounds of CE selection) and the dissociation constants reached 10-8 M level. The hybrid selection approach exhibited several significant advantages, including speed, affinity, specificity, and avoiding negative selection. Using one of the selected ALP-binding aptamers as an affinity ligand, feasibility for real application of the selected aptamers was demonstrated through constructing an improved enzyme activity assay.

Efficacy of non-pharmacological interventions for primary dysmenorrhoea: a systematic review and Bayesian network meta-analysis.

OBJECTIVES: To assess the relative benefits of various non-pharmacological interventions on treating primary dysmenorrhoea within a network meta-analysis. STUDY DESIGN: Systematic review and Bayesian network meta-analysis. INCLUSION CRITERIA: Randomised controlled trial involving patient with primary dysmenorrhoea and received non-pharmacological interventions. DATA SOURCES: Four databases (Medline, Embase, Cochrane Library and Web of Science) were searched from inception to October first, 2022. RISK-OF-BIAS ROB ASSESSMENT: RoB 2.0 assessment tools was used to assess the risk of bias in the included studies. SYNTHESIS OF RESULTS: Conventional meta-analysis was conducted by pairwise comparison between non-pharmacological therapy and control treatment. The Bayesian network meta-analysis was conducted by the Aggregate Data Drug Information System Software based on the consistency or inconsistency model, and rank probability was used to indicate the priority of non-pharmacological therapy. RESULTS: 33 studies involving eight non-pharmacological interventions were included. With regard to conventional meta-analysis, we selected Visual Analogue Scale (VAS) as primary outcome to evaluate the pain intensity. The result showed that eight interventions (Exercise, Herb, Acupuncture, Aromatherapy, Transcutaneous Electrical Nerve Stimulation, Topical heat, Acupressure, Yoga) displayed positive effect on reduction of menstrual pain compared with placebo or no treatment. A Bayesian network meta-analysis revealed that exercise -3.20 (95% CI -4.01 to -2.34), acupuncture -2.90 (95% CI -3.97 to -2.85) and topical heat -2.97 (95% CI -4.66 to -1.29) probably resulted in a reduction in pain intensity (VAS) . CONCLUSIONS: Non-pharmacological interventions may result in a reduction or slight reduction in pain intensity compared with no treatment or placebo. Specifically, exercise and acupuncture are considered as potentially effective non-pharmacological treatments in short-term treatment. Indeed, larger and better methodological quality research is needed. TRIAL REGISTRATION NUMBER: CRD42022351021.

Dietary Immunoglobulin Y by Targeting Both GbpB and GtfB Enhances the Anticaries Effect in Rats.

OBJECTIVE: The purpose of this work was to develop an anti-CAT-SYI immunoglobulin Y (IgY) antibody that targeted both GtfB (glucosyltransferase B) and GbpB (glucan-binding protein B) and test its anticaries properties in rats. METHODS: A new CAT-SYI fusion gene was created utilising functional DNA fragments from the GtfB and GbpB genes. The recombinant antigens, comprising the fused CAT-SYI antigen, GtfB, and GbpB, were expressed and purified using a prokaryotic expression and purification system. The purified recombinant antigens were utilised to immunise laying hens against particular IgY production. The biological activities of these particular IgY antibodies were then assessed both in vitro and in vivo, including their capacity to suppress biofilm formation and tooth caries. RESULTS: Results indicated that these produced IgY antibodies demonstrated a high antibody titer (>0.1 µg/mL) and could precisely recognise and bind to their respective antigens. Furthermore, it was discovered that these specific IgY antibodies successfully bind to Streptococcus mutans and significantly reduce biofilm development. After 8 weeks of ingesting antigen-specific IgY meals, comprising anti-GtfB IgY and anti-GbpB IgY, the severity of dental caries was dramatically reduced in S mutans-infected Sprague-Dawley rats (P < .01). Anti-CAT-SYI IgY therapy significantly reduced tooth cavities by 89.0% in vivo (P < .05) compared to other treatment groups. CONCLUSIONS: The anti-CAT-SYI IgY, a multitarget antibody that targets both GtfB and GbpB, displayed excellent inhibitory effects against S mutans, making it a promising targeted method with improved anticaries efficacy and significant application opportunities.

Research and Progress of Inorganic Infrared Electrochromic Materials and Devices.

BACKGROUND: Electrochromic materials can dynamically change their optical properties (such as transmittance, absorbance, and reflectance under the action of an applied voltage, and their research and application in the visible band have been widely concerned. In recent years, with the continuous development of electrochromic technology, the related research has been gradually extended to the infrared region. OBJECTIVE: This invited review aims to provide an overview of the current status of several inorganic infrared electrochromic materials, to provide some references for future research, and to promote the research and application of electrochromic technology in the infrared region. METHODS: This review summarizes various research results in the field of infrared electrochromic, which includes a detailed literature review and patent search. Starting from the key performance parameters and device structure characteristics of infrared electrochromic devices (ECDs), the research and progress of several types of inorganic infrared electrochromic materials, including metal oxides, plasma nanocrystals, and carbon nanomaterials, are mainly presented, and feasible optimization directions are also discussed. CONCLUSION: We believe that the potential of these materials for civilian and military applications, for example, infrared electrochromic smart windows, infrared stealth/disguise, and thermal control of spacecraft, can be fully exploited by optimizing the materials and their devices to improve their performance.

Brave the Wind and the Waves: Discovering Robust and Generalizable Graph Lottery Tickets.

The training and inference of Graph Neural Networks (GNNs) are costly when scaling up to large-scale graphs. Graph Lottery Ticket (GLT) has presented the first attempt to accelerate GNN inference on large-scale graphs by jointly pruning the graph structure and the model weights. Though promising, GLT encounters robustness and generalization issues when deployed in real-world scenarios, which are also long-standing and critical problems in deep learning ideology. In real-world scenarios, the distribution of unseen test data is typically diverse. We attribute the failures on out-of-distribution (OOD) data to the incapability of discerning causal patterns, which remain stable amidst distribution shifts. In traditional spase graph learning, the model performance deteriorates dramatically as the graph/network sparsity exceeds a certain high level. Worse still, the pruned GNNs are hard to generalize to unseen graph data due to limited training set at hand. To tackle these issues, we propose the Resilient Graph Lottery Ticket (RGLT) to find more robust and generalizable GLT in GNNs. Concretely, we reactivate a fraction of weights/edges by instantaneous gradient information at each pruning point. After sufficient pruning, we conduct environmental interventions to extrapolate potential test distribution. Finally, we perform last several rounds of model averages to further improve generalization. We provide multiple examples and theoretical analyses that underpin the universality and reliability of our proposal. Further, RGLT has been experimentally verified across various independent identically distributed (IID) and out-of-distribution (OOD) graph benchmarks.

Identification of metabolic profiling of cell culture of licorice compared with its native one.

Glycyrrhiza uralensis has long been used as a flavoring and sweetening agent in food products. In the last ten years, suspensions of Glycyrhiza cells have been successfully established. However, there is no report of full metabolic profiling research on these cells. To identify their composition we used HPLC-DAD coupled with ESI(+/-)-MS (n) to compare the constituents of cultured Glycyrhiza (CG) cells with those the native cells (NG). We identified 60 compounds including flavonoids, phenols, and triterpenoids. Among these compounds, 42 occurred both in NG and CG, nine were present in NG only and nine were present in CG alone. The number of the triterpenoid aglycones without glycones in CG was smaller than that in NG. The number of flavanone, isoflavone, isoflavan, and benzenoid compounds was also smaller in CG than that in NG, whereas the number of pterocarpans was much higher. Although differences existed between CG and NG, the extract of CG was similar to that of NG. With the development of cell suspension culture-based biotransformation, cell culture of Glycyrrhiza has the potential to be more profitable than field cultivation in some areas.