Increased expression of TIGIT and KLRG1 correlates with impaired CD56bright NK cell immunity in HPV16-related cervical intraepithelial neoplasia.

BACKGROUND: The onset and progression of cervical intraepithelial neoplasia (CIN) are closely associated with the persistent infection of high-risk HPV (especially type16), which is mainly caused by immune escape. Natural killer (NK) cells play an important role against virally infected cells and tumor cells through a fine balance of signals from multiple surface receptors. Overexpression of non-MHC-I specific inhibitory receptors TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a on NK cells correlates with cellular exhaustion and immune evasion, but these receptors have not been investigated in CIN. The aim of the present study was to examine the potential role of NK cell non-MHC-I specific inhibitory receptors expression in immune escape from HPV16(+)CIN patients. METHODS: The subset distribution, IFN-γ and TNF-α expression levels and immunophenotype of TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a of NK cells were investigated in peripheral blood mononuclear cell samples by flow cytometry from 82 women who were HPV16(+) with CIN grades 0, I, II-III or HPV(-) CIN 0. Immunohistochemistry was applied to detect the expression of ligands for NK receptors in the cervical tissues. HPV types were identified by PCR assays. RESULTS: The HPV16(+) subjects with high-grade lesions had an increased number of circulating peripheral blood CD56bright NK cells with reduced functionality and IFN-γ secretion. The expression levels of the inhibitory molecules TIGIT and KLRG1 on CD56bright NK cells increased in parallel with increasing CIN grade. In addition, TIGIT and KLRG1 related ligands, Poliovirus receptor (PVR), N-Cadherin and E-Cadherin expression level was also elevated with increasing CIN grade. CONCLUSIONS: Our results suggest that up-regulation of the inhibitory TIGIT, KLRG1 and their ligands may negatively regulate cervical CD56bright NK-mediated immunity to HPV16 and contribute to the progression of CIN. These results may facilitate the development of early-warning immune predictors and therapeutic strategies for HPV16(+) CIN based on the TIGIT and KLRG1 inhibitory pathways of NK cells.

Leafhopper Wing-Inspired Broadband Omnidirectional Antireflective Embroidered Ball-Like Structure Arrays Using a Nonlithography-Based Methodology.

Leafhoppers (Thaia rubiginosa) actively coat their wings with embroidered ball-like secretory brochosomes, which act as antireflective structures to enhance camouflage against predators. Inspired by the leafhoppers, we report a scalable nonlithographic approach for self-assembling nonclose-packed embroidered ball-like hierarchical structure arrays. The resulting structures create a gradual refractive index transition at the air/substrate interface, thereby suppressing the optical reflection for wide viewing angles. Compared with a bare substrate, the average reflectance of the structured substrate in the whole visible spectral region is reduced from 9 to 3% at normal incidence, and the average reflectance of that is even reduced by ca. 22% as the incident angle reaches 75°. Moreover, the dependence of the height and the shape of the hierarchical structure on the omnidirectional antireflection performance is systemically evaluated in this research.

Development and validation of a risk nomogram to estimate risk of hyponatremia after spinal cord injury: A retrospective single-center study.

OBJECTIVE: This study aimed to establish a nomogram-based assessment for predicting the risk of hyponatremia after spinal cord injury (SCI). DESIGN: The study is a retrospective single-center study. PARTICIPANTS: SCI patients hospitalized in the First Affiliated Hospital of Guangxi Medical University. SETTING: The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. METHODS: We performed a retrospective clinical study to collect SCI patients hospitalized in the First Affiliated Hospital of Guangxi Medical University from 2016 to 2020. Based on their clinical scores, the SCI patients were grouped as either hyponatremic or non-hyponatremic, SCI patients in 2016-2019 were identified as the training set, and patients in 2020 were identified as the test set. A nomogram was generated, the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to validate the model. RESULTS: A total of 895 SCI patients were retrieved. After excluding patients with incomplete data, 883 patients were finally included in this study and used to construct the nomograms. The indicators used in the nomogram included sex, completeness of SCI, pneumonia, urinary tract infection, fever, constipation, white blood cell (WBC), albumin and serum Ca2+. These indices were determined by the least absolute shrinkage and selection operator (LASSO) regression analysis. The C-index of the model was 0.81, the area under the curve (AUC) of the training set was 0.82(Cl:0.79-0.85), and the validation set was 0.79(Cl:0.73-0.85). CONCLUSIONS: Nomogram has good predictive ability, sex, completeness of SCI, pneumonia, urinary tract infection, fever, constipation, WBC, albumin and serum Ca2+ were predictors of hyponatremia after SCI.

Oral Health Status and Literacy/Knowledge Amongst Pregnant Women in Shanghai.

BACKGROUND: The changes in hormones, diet, and hygiene associated with pregnancy are associated with oral diseases. There is insufficient awareness of the importance of oral health during pregnancy. This study investigated the oral health status and knowledge amongst pregnant women in Shanghai. METHODS: This cross-sectional study enrolled pregnant women at the Shanghai Red House Obstetrics & Gynecology Hospital in December 2020. The Fourth National Oral Health Questionnaire was used to evaluate the oral health status. Decayed/missing/filled teeth (DMFT) were the sum of the number of decayed, missing due to caries, and filled teeth. The chi-square test and Kruskal-Wallis test were used to compare the groups. RESULTS: A total of 224 pregnant women were enrolled. The rates of dental caries were 69.8%, periodontal health was 1.8%, calculus detection was 95.6%, shallow periodontal pocket was 51.1%, deep periodontal pocket was 4.9%, regular oral examination was 22.8%, correct brushing was 49.6%, and prepregnancy oral examination was 20.1%. DMFT was 2.27, and the caries filling ratio was 45.4%. The number of missing teeth increased with age (P < .001). Only 26.3% used dental floss more than once a day, 47.3% rinsed the mouth more than twice a day, and 46.9% cleaned their tongue coating every week. In addition, 99% of the pregnant women agreed that "oral health was vital to their lives" and 97.7% agreed that "regular oral examination was necessary." CONCLUSIONS: The oral health status amongst pregnant women in Shanghai was poor, but oral health awareness and attitudes were relatively high.

Systematically Investigating the Pharmacological Mechanism of Momordica grosvenori in the Treatment of Spinal Cord Injury by Network Pharmacology and Experimental Verification.

Objective: This study aimed to explore the molecular mechanism of Momordica grosvenori (MG) in spinal cord injury (SCI) by network pharmacology analysis. Methods: We searched for potential active MG compounds using the TCMSP database and the BATMAN-TCM platform. The Swiss target prediction database was used to find MG-related targets and the targets of SCI from the CTD, GeneCards, and DrugBank databases. Following that, a protein-protein interaction (PPI) study was carried out. Cytoscape software was used to calculate the hub gene, and R software was used to evaluate the Gene Ontology (GO) and KEGG enrichment pathways. Finally, molecular docking between the hub protein and important compounds was performed. We verified STAT3, MAPK1, HSP90AA1, PIK3R1, PIK3CA, and RXRA potential targets by quantitative PCR. Results: We obtained 293 MG-anti-SCI targets with potential therapeutic utility by intersecting 346 MG-related targets and 7214 SCI-related targets. The top 10 identified genes, ranking in descending order of value, were SRC, STAT3, MAPK1, HSP90AA1, PIK3R1, PIK3CA, RXRA, AKT1, CREBBP, and JAK2. Through enrichment analysis and literature search, 10 signaling pathways were screened out. The molecular docking of important drugs and hub targets revealed that some had a higher binding affinity. The results of quantitative PCR indicated that MAPK1, RXRA, and STAT3 were expressed differently in in vitro experiments. Conclusion: In conclusion, the current work indicated that MG might play an anti-SCI role via multicomponent, multitarget, and multichannel interaction, which presents a novel idea for further research into the precise mechanism of MG-anti-SCI interaction.

Phosphine-mediated domino benzannulation strategy for the construction of highly functionalized multiaryl skeletons.

A skeleton crew: A phosphine-mediated domino benzannulation strategy was developed for the synthesis of multiaryl skeletons (see scheme). A wide range of aromatic compounds and functional groups can be assembled into a multiaryl molecule through a core domino process.

Phosphine-catalyzed domino reaction: an efficient method for the synthesis of highly functionalized spirooxazolines.

A novel phosphine-catalyzed intermolecular [3 + 2] cycloaddition of ynones and N-substituted isatins was developed. In this reaction, substituted ynones, serving as a C(3) synthon, were successfully applied in intermolecular annulation reactions. A number of functionalized spirooxazolines were obtained in high yields and stereoselectivity.

Application of a Systematic Oral Health Promotion Model for Pregnant Women: A Randomised Controlled Study.

PURPOSE: To explore the effects of oral health promotion management on the improvement of oral healthcare knowledge, attitudes, and behaviours in pregnant women. MATERIALS AND METHODS: This randomised study included pregnant women in Shanghai (China) who were randomly assigned to receive oral-health promotion management (intervention group) or no interventions (control group). The primary outcome for this study was overall oral health. The secondary outcomes included oral health awareness and attitudes, oral health knowledge, oral healthcare behaviours, medical visits, and risk factors. The Fourth National Oral Health Questionnaire was self-administered in this study, and oral examinations included caries and periodontal status. Data consistency was assessed by the Kappa coefficient. RESULTS: After intervention, periodontal outcomes in the intervention group had improved statistically significantly, and the proportion of those without periodontal diseases had statistically significantly increased to 14.4% (p < 0.05). In the intervention group, statistically significant improvements were also observed in the number of active caries (p < 0.001), number of filled teeth (p = 0.014), and community periodontal index (CPI) scores (p < 0.001). Overall, after intervention, pregnant women demonstrated comprehension of the importance of children's deciduous teeth, and their knowledge of the importance of good oral health had greatly improved. Further, oral healthcare habits in the intervention group also showed statistically significant improvement: 56.8% established the habit of cleaning the tongue every week (p < 0.05) and 39.6% established the habit of regular oral examination (p < 0.05). CONCLUSION: Oral healthcare education and promotion management for pregnant women can effectively improve their oral health, knowledge, attitudes, and behaviours of oral health care.

The ß-catenin/CBP signaling axis participates in sepsis-induced inflammatory lung injury.

Sepsis-induced inflammatory lung injury is a key factor causing failure of the lungs and other organs, as well as death, during sepsis. In the present study, a caecal ligation and puncture (CLP)-induced sepsis model was established to investigate the effect of ß-catenin on sepsis-induced inflammatory lung injury and the corresponding underlying mechanisms. C57BL/6 mice were randomly divided into five groups, namely, the sham, CLP, ß-catenin knockout (KO) + CLP, XAV-939 + CLP, and ICG-001 + CLP groups; the XAV-939 + CLP and ICG-001 + CLP groups were separately subjected to intraperitoneal injections of the ß-catenin inhibitors XAV-939 and ICG-001 for 1 week preoperatively and 2 days postoperatively, respectively. Forty-eight hours after CLP, we measured ß-catenin expression in lung tissues and evaluated mouse mortality, histopathological characteristics of hematoxylin and eosin (H&E)-stained lung tissues, serum cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-10, and IL-1ß) levels, lung myeloperoxidase (MPO) activity, and the number of apoptotic cells in the lung tissues. Our results indicated that both the inhibition of ß-catenin expression and blockage of ß-catenin/CREB-binding protein (CBP) interactions by ICG-001 effectively decreased mouse mortality, alleviated pathological lung injury, and reduced the serum TNF-α, IL-10, and IL-1ß levels, in addition to reducing the lung MPO activity and the number of apoptotic cells in lung tissues of the sepsis model mice. Therefore, it can be deduced that the ß-catenin/CBP signaling axis participates in regulating sepsis-induced inflammatory lung injury.

Effect of immunotherapy on the immune microenvironment in advanced recurrent cervical cancer.

This study evaluated the basic immune status of cervical cancer and the influences of immunotherapy on the immune microenvironment, and analyzed the correlation between changes in the immune microenvironment and prognosis. We retrospectively analyzed the treatment status of 8 patients with advanced recurrent cervical cancer treated with PD-1 inhibitors and detected the tumor-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, and PD-L1) by immunohistochemistry. All patients showed good tolerance during the treatment. Complete response (CR), partial response (PR) and stable disease (SD) was observed in 3, 2, and 3 patients, respectively. Immunohistochemical analysis showed immunotherapy resulted in increased infiltration of T lymphocytes, natural killer cells, and B cells, especially among those who responded well. The expression of B cells in 4 of the 5 patients with clinical benefit was relatively high, and the expression of PD-L1 in these 5 patients showed a combined positive score > 3. PD-L1 expression increased significantly after treatment with PD-1 inhibitors. Second-generation sequencing showed that the tumor mutation burden of two patients with adenocarcinoma was high, and after immunotherapy, one case recurred after cure and the other remained stable. PR was also observed in squamous cell carcinoma patients with dMMR (p.R2165H/c.6494G > A) and PIK3CA (p.E545K(E9)) mutations. The expression of B cells and PD-L1 has certain predictive effect for the efficacy of immunotherapy in cervical cancer under the condition of high or low T cell infiltration, and can inform treatment decision-making for patients with advanced cervical cancer.

Omnidirectional / Unidirectional Antireflection-Switchable Structures Inspired by Dragonfly Wings.

Randomly arranged irregular inclined conical structure-covered dragonfly wings, distinguished from periodic conical structure-covered cicada wings, are with high optical transparency for wide viewing angles. Bioinspired by the antireflective structures, we develop a colloidal lithography approach for engineering randomly arranged irregular conical structures with shape memory polymer-based tips. The structures establish a gradual refractive index transition to suppresses optical reflection in the visible spectrum. By manipulating the configuration of structure tips through applying common solvent stimulations or contact pressures under ambient conditions, the resulting unidirectional antireflection and omnidirectional antireflection performances are able to be instantaneously and reversibly switched. The dependences of structure shape, structure inclination, structure arrangement, and structure composition on the switchable antireflection capability are also systematically investigated in this study.

Domino reaction for the chemo- and stereoselective synthesis of trans-2,3-dihydrobenzofurans from N-thiophosphinyl imines and sulfur ylides.

A novel domino annulation between sulfur ylides and salicyl N-thiophosphinyl imines was developed. The method allows the synthesis of a highly substituted trans-2,3-dihydrobenzofuran skeleton with high yield and excellent chemo- and stereoselectivity.

Highly efficient asymmetric vinylogous Mannich reaction induced by O-pivaloylated D-galactosylamine as the chiral auxiliary.

The diastereospecific formation of ß-N-glycoside-linked α-amino-2(5H)-furanone has been achieved with high yield via a vinylogous Mannich reaction. The reaction was performed by using O-pivaloylated galactosylamine 1 as a chiral template and ZnCl(2)·Et(2)O as a promoter in Et(2)O. Imines 3 of aromatic compounds and trimethylsiloxyfuran 4 were converted to N-galactosyl α-amino-2(5H)-furanone 5, giving ratios of diastereomers higher than 20:1. This procedure provides rapid access to biologically important γ-butenolide derivatives.

N-heterocyclic carbene-catalyzed (NHC) three-component domino reactions: highly stereoselective synthesis of functionalized acyclic ε-ketoesters.

A novel NHC-catalyzed three-component domino strategy to access high functionalized cis-ε-ketoesters with excellent yields (up to 98%) and high stereoselectivities (up to 20:1) is documented. The title domino reactions are atom economical and work on a broad range of substrates. The relative stereochemistry could be explained by a cascade crossed-benzoin/oxy-Cope rearrangement/esterification process. The thus-obtained products are of potential synthetic value in the drug research and combinatorial chemistry.

Bifunctional primary amine-thiourea-TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst: the asymmetric synthesis of dihydropyrimidines.

An enantioselective Biginelli reaction has been developed by using a bifunctional primary amine-thiourea-TfOH (BPAT·TfOH) as a chiral phase-transfer catalyst and t-BuNH(2)·TFA as an additive in saturated brine at room temperature. The corresponding dihydropyrimidines were obtained in moderate-to-good yields with up to 99% ee under mild conditions. A plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

Highly diastereoselective vinylogous Mukaiyama aldol reaction of α-keto phosphonates with 2-(trimethylsilyloxy)furan catalyzed by Cu(OTf)2.

The diastereospecific formation of δ-hydroxyalkylbutenolide phosphonate has been achieved via a vinylogous Mukaiyama aldol reaction. The reaction was performed using α-ketophosphonate 1 and 2-(trimethylsilyloxy)furan 2 mediated by Cu(OTf)(2) and 2,2,2-trifluoroethanol as additive in CH(2)Cl(2). The reaction proceeds rapidly and affords the corresponding 5-(hydroxy(aryl)methyl) furan-2(5H)-one phosphonates 3 in high yields with good to excellent diastereoselectivities (d.r. up to >99 : 1). 5-(Hydroxy(alkyl)methyl)furan-2(5H)-one phosphonates could also be obtained with good diastereoselectivities.

Bifunctional phosphine-catalyzed cross-Rauhut-Currier/Michael/aldol condensation triple domino reaction: synthesis of functionalized cyclohexenes.

A novel bifunctional phosphine-catalyzed reaction was developed. Cross-Rauhut-Currier, Michael and aldol reactions were successfully combined into a domino process. This method offers a powerful approach to the construction of highly substituted cyclohexene skeletons.

Reversibly Erasable Broadband Omnidirectional Antireflection Coatings Inspired by Inclined Conical Structures on Blue-Tailed Forest Hawk Dragonfly Wings.

Blue-tailed forest hawk dragonfly (Orthetrum triangulare) wings, covered with inclined conical structures, are studied for their high transparency and low reflectance for large viewing angles. However, limited by existing technologies, the exquisite inclined structures are not replicated easily or applied adequately. Here, we combine a shear-induced self-assembly approach and a colloidal lithography technology to create omnidirectional antireflection structures that are inspired by dragonfly wings. Nonclose-packed colloid crystals are spin-coated and serve as structural templates in a plasma etching procedure to pattern subwavelength inclined conical structures directly on shape memory polymer-coated substrates. The dependence of the antireflection functionality on the shape and inclination of conical structures is systematically investigated in this research. Compared with a featureless substrate, the structure-covered substrate can display an approximately 8% higher average transmittance in the visible wavelength range at normal incidence and even approximately 23% higher average transmittance as the incident angle increases to 75°. Moreover, the reconfigurable structures composed of shape memory polymers can be repeatedly deformed and recovered as a result of external stimuli at ambient conditions, and the corresponding broadband omnidirectional antireflection functionality is therefore reversibly erased and restored.

Efficient syntheses of phosphonylated isochromenes by regioselective 6-endo-dig addition to carbon-carbon triple bond catalyzed by Pd(OAc)2.

Palladium(II)-catalyzed cycloisomerization of [(2-alkynylphenyl)hydroxymethyl]phosphonates 6 provides an efficient route to phosphonylated isochromenes 7 in THF at room temperature and the reaction proceeded in a regioselective manner leading to the 6-endo-dig products 7 in moderate to excellent yields.

The diastereoselective synthesis of methyl 5-deoxy-5-(dialkylphosphono)-5-(dialkylphosphorylamido)-2,3-O-isopropylidene-beta-D-ribofuranosides.

A convenient method has been developed for the diastereoselective synthesis of methyl 5-deoxy-5-(dialkylphosphono)-5-(dialkylphosphorylamido)-2,3-O-isopropylidene-beta-d-ribofuranosides under mild conditions, namely the reaction of a dialkyl phosphoramidate with a dialkyl phosphite and methyl 2,3-O-isopropylidene-beta-D-ribo-pentodialdo-1,4-furanoside in acetyl chloride in a one-pot procedure.