Low platelet count at diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis is correlated with the severity of disease and renal prognosis.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease that involves inflammation of blood vessels. There is increasing evidence that platelets play a crucial role not only in hemostasis but also in inflammation and innate immunity. In this study, we explored the relationship between platelet count, clinical characteristics, and the prognosis of patients with AAV. We divided 187 patients into two groups based on their platelet count. Clinicopathological data and prognostic information were retrospectively gathered from medical records. Univariate and multivariate regression analyses were used to identify risk factors for prognosis, including end-stage renal disease (ESRD) and mortality. The cutoff point for platelet count was set at 264.5 × 109/L, as determined by the receiver operating characteristic (ROC) curve for predicting progression to ESRD in patients with AAV. We observed patients with low platelet count (platelets < 264.5 × 109/L) had lower leukocytes, hemoglobin, complement, acute reactants, and worse renal function (P for eGFR < 0.001). They were also more likely to progress to ESRD or death compared to the high platelet count group (platelets > 264.5 × 109/L) (P < 0.0001, P = 0.0338, respectively). Low platelet count was potentially an independent predictor of poor renal prognosis in the multivariate regression analysis [HR 1.670 (95% CI 1.019-2.515), P = 0.014]. Lower platelet count at diagnosis is associated with more severe clinical characteristics and impaired renal function. Therefore, platelet count may be an accessible prognostic indicator for renal outcomes in patients with AAV.

Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma.

BACKGROUND: The pattern recognition receptor Dectin-1 was initially discovered to play a pivotal role in mediating pulmonary antifungal immunity and promoting neutrophil-driven inflammation. Recent studies have revealed that Dectin-1 is overexpressed in asthma, but the specific mechanism remains elusive. Additionally, Dectin-1 has been implicated in promoting pyroptosis, a hallmark of severe asthma airway inflammation. Nevertheless, the involvement of the non-classical pyroptosis signal caspase-11/4 and its upstream regulatory mechanisms in asthma has not been completely explored. METHODS: House dust mite (HDM)-induced mice was treated with Dectin-1 agonist Curdlan, Dectin-1 inhibitor Laminarin, and caspase-11 inhibitor wedelolactone separately. Subsequently, inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed. Western blotting was performed to measure the protein expression of caspase-11 and gasdermin D (GSDMD). Cell pyroptosis and the expression of chemokine were detected in vitro. The correlation between Dectin-1 expression, pyroptosis factors and neutrophils in the induced sputum of asthma patients was analyzed. RESULTS: Curdlan appeared to exacerbate neutrophil airway inflammation in asthmatic mice, whereas wedelolactone effectively alleviated airway inflammation aggravated by Curdlan. Moreover, Curdlan enhanced the release of caspase-11 activation fragments and N-terminal fragments of gasdermin D (GSDMD-N) stimulated by HDM both in vivo or in vitro. In mouse alveolar macrophages (MH-S cells), Curdlan/HDM stimulation resulted in vacuolar degeneration and elevated lactate dehydrogenase (LDH) release. In addition, there was an upregulation of neutrophil chemokines CXCL1, CXCL3, CXCL5 and their receptor CXCR2, which was suppressed by wedelolactone. In asthma patients, a positive correlation was observed between the expression of Dectin-1 on macrophages and caspase-4 (the human homology of caspase-11), and the proportion of neutrophils in induced sputum. CONCLUSION: Dectin-1 activation in asthma induced caspase-11/4 mediated macrophage pyroptosis, which subsequently stimulated the secretion of chemokines, leading to the exacerbation of airway neutrophil inflammation.

C5a enhances inflammation and chemotaxis of γδ T cells in malignant pleural effusion.

BACKGROUND: The inhibitory effect of γδT17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding regarding the phenotypic characterization of γδ T cells in MPE patients and their recruitment to the pleural cavity. METHODS: We quantified γδ T cell prevalence in pleural effusions and corresponding peripheral blood from malignant and benign patients using immunohistochemistry and flow cytometry. The expression of effector memory phenotype, stimulatory/inhibitory/chemokine receptors and cytokines on γδ T cells in MPE was analyzed using multicolor flow cytometry. The infiltration of γδ T cells in MPE was assessed through immunofluorescence, ELISA, flow cytometry and transwell migration assay. RESULTS: We observed a significant infiltration of γδ T cells in MPE, surpassing the levels found in blood and benign pleural effusion. γδ T cells in MPE exhibited heightened expression of CD56 and an effector memory phenotype, while displaying lower levels of PD-1. Furthermore, γδ T cells in MPE showed higher levels of cytokines (IFN-γ, IL-17A and IL-22) and chemokine receptors (CCR2, CCR5 and CCR6). CCR2 expression was notably higher in the Vδ2 subtype compared to Vδ1 cells. Moreover, the complement C5a enhanced cytokine release by γδ T cells, upregulated CCR2 expression in Vδ2 subsets, and stimulated the production of chemokines (CCL2, CCL7 and CCL20) in MPE. In vitro utilizing CCR2 neutralising and C5aR antagonist significantly reduced the recruitment of γδ T cells. CONCLUSIONS: γδ T cells infiltrate MPE by overexpressing CCR2 and exhibit hightened inflammation, which is further augmented by C5a.

[Effect of different kinds of gingival retraction agents on the polymerization inhibition of polyvinyl siloxane impression materials].

PURPOSE: To evaluate the effect of different kinds of gingival retraction agents after directly contacted with polyvinyl siloxane impression materials on polymerization inhibition and the inhibition degree. METHODS: Five kinds of gingival retraction agents (0.1% epinephrine hydrochloride, 0.05% oxymetazoline, 15.5% ferric sulfate, 25% aluminum chloride and 5% aluminum chloride) were chosen, normal saline was as control group, and two kinds of polyvinyl siloxane impression materials (ExpressTM, ImprintTM Ⅱ) were combined into 12 groups. There were 12 specimens in each group and 144 specimens in total. Silicone rubber impression materials were mixed by the same operator using a dispensing gun into the acrylic mold, so that they could directly contact the gingival retraction agents on the densely woven cotton fabrics. The samples were removed when the polymerization time arrived according to the manufactures' recommendations and then placed under a stereomicroscope with a magnification of 10 times to observe whether polymerization inhibition occurred, the degree of inhibition was compared afterwards. SPSS 22.0 software package was used for statistical analysis. RESULTS: The polymerization inhibition of two kinds of silicone rubber impression materials occurred in 15.5% ferric sulfate group and 25% aluminum chloride group, and the inhibition occurrence rate was 100%, the difference was statistically significant (P＜0.05) compared with normal saline group. Inhibition was not found in 0.1% epinephrine hydrochloride group, 0.05% oxymetazoline group and 5% aluminum chloride. The effect of 15.5% ferric sulfate and 25% aluminum chloride on polymerization inhibition degree of ImprintTM Ⅱ was greater than ExpressTM, and the difference was statistically significant(P＜0.05). CONCLUSIONS: When silicone rubber impression material is used during impression procedure, attention should be paid to the effect of the gingival retraction agent containing 15.5% ferric sulfate and 25% aluminum chloride on its polymerization. The gingival retraction agent should be washed before impression to avoid the residue directly contacting the silicone rubber to prevent polymerization.

Urinary isomorphic red blood cells for the prediction of disease severity and renal outcomes in MPO-ANCA-associated vasculitis: a retrospective cohort study.

BACKGROUND: Hematuria is common in myeloperoxidase anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-MPO). Previous studies have mainly focused on urinary dysmorphic red blood cells and few have reported the clinical significance of isomorphic urinary red blood cells. Therefore, the main aim of this study was to assess the predictive yield  of urinary isomorphic red blood cells for disease severity and renal outcomes in patients with ANCA-MPO associated vasculitis. METHODS: A total of 191 patients with ANCA-MPO associated vasculitis with hematuria were retrospectively selected and were divided into two groups (with isomorphic red blood cells versus dysmorphic red blood cells) according to the percentage of isomorphic red blood cells on urinary sediment analysis. Clinical, biological and pathological data at diagnosis were compared. Patients were followed up for a median of 25 months and progression to end-stage kidney disease and death were regarded as main outcome events. Additionally, univariate and multivariate Cox regression models were used to estimate the risk factors for end-stage kidney disease. RESULTS: Out of 191 patients, 115 (60%) had ≥ 70% and 76 (40%) had < 30% urine isomorphic red blood cells. Compared with patients in the dysmorphic red blood cell group, patients in the isomorphic red blood cell group had a significantly lower estimated glomerular filtration rate (eGFR) [10.41 mL/min (IQR 5.84-17.06) versus 12.53 (6.81-29.26); P = 0.026], higher Birmingham Vasculitis Activity Score [16 (IQR 12-18) versus 14 (10-18); P = 0.005] and more often received plasma exchange [40.0% versus 23.7% (P = 0.019)] at diagnosis. Kidney biopsies revealed a higher proportion of patients with glomerular basement membrane fracture in the isomorphic red blood cell group [46.3% versus 22.9% (P = 0.033)]. Furthermore, patients with predominant urinary isomorphic red blood cells were more likely to progress to end-stage kidney disease [63.5% versus 47.4% (P = 0.028)] and had a higher risk of death [31.3% versus 19.7% (P = 0.077)]. The end-stage kidney disease-free survival was lower in patients in the isomorphic red blood cell group (P = 0.024). However, urine isomorphic red blood cells ≥ 70% could not predict the presence of end-stage kidney disease in multivariate Cox analysis. CONCLUSION: Myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis patients with predominant urinary isomorphic red blood cells at diagnosis had more severe clinical manifestations and a higher risk of poor renal outcomes. In this respect, urinary isomorphic red blood cells could be viewed as a promising biomarker of ANCA_MPO vasculitis severity and progression.

Macrocyclization of linear molecules by deep learning to facilitate macrocyclic drug candidates discovery.

Interest in macrocycles as potential therapeutic agents has increased rapidly. Macrocyclization of bioactive acyclic molecules provides a potential avenue to yield novel chemical scaffolds, which can contribute to the improvement of the biological activity and physicochemical properties of these molecules. In this study, we propose a computational macrocyclization method based on Transformer architecture (which we name Macformer). Leveraging deep learning, Macformer explores the vast chemical space of macrocyclic analogues of a given acyclic molecule by adding diverse linkers compatible with the acyclic molecule. Macformer can efficiently learn the implicit relationships between acyclic and macrocyclic structures represented as SMILES strings and generate plenty of macrocycles with chemical diversity and structural novelty. In data augmentation scenarios using both internal ChEMBL and external ZINC test datasets, Macformer display excellent performance and generalisability. We showcase the utility of Macformer when combined with molecular docking simulations and wet lab based experimental validation, by applying it to the prospective design of macrocyclic JAK2 inhibitors.

Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1.

Inorganic arsenic (iAs) has been a human health concern and is associated with intestinal malignancies. However, the molecular mechanisms of the iAs-induced oncogenic process in intestine epithelial cells remain elusive, partly because of the known hormesis effect of arsenic. Here, we established that six-month exposure to iAs at a concentration similar to those found in contaminated drinking water could promote malignant characteristics, including enhanced proliferation and migration, resistance to apoptosis, and mesenchymal-like transition in Caco-2 cells. Transcriptome analysis and mechanism study revealed that key genes and pathways involved in cell adhesion, inflammation and oncogenic regulation were altered during chronic iAs exposure. Specifically, we uncovered that down-regulation of HTRA1 was essential for the iAs-induced acquisition of the cancer hallmarks. Further, we evidenced that the loss of HTRA1 during iAs-exposure could be restored by HDAC6 inhibition. Caco-2 cells with chronic exposure to iAs exhibited enhanced sensitivity to WT-161, a specific inhibitor of HDAC6, when used alone than in combination with a chemotherapeutic agent. These findings provide valuable information for understanding the mechanisms of arsenic-induced carcinogenesis and facilitating the health management of populations in arsenic-polluted areas.

Efficacy of WWQ-131, a highly selective JAK2 inhibitor, in mouse models of myeloproliferative neoplasms.

Hyperactivation of the Janus kinase 2 (JAK2) signaling pathway leads to myeloproliferative neoplasms (MPNs) and targeting JAK2 can be used as an effective strategy for the treatment of MPNs. Here, our study indicated that WWQ-131 was a highly selective JAK2 inhibitor (IC50 =2.36 nM), with 182-fold and 171-fold more selective to JAK1 and JAK3, respectively. In JAK2V617F-dependent cell lines, WWQ-131 efficaciously inhibited cell proliferation, induced cell cycle arrest at the G2/M phase and apoptosis, and blocked the aberrant activation of JAK2 signaling pathway. In a mouse Ba/F3_JAK2V617F driven disease model, WWQ-131 effectively suppressed STAT5 phosphorylation in spleen and liver, and inhibited Ba/F3_JAK2V617F cells spreading and proliferation in vivo. In addition, WWQ-131 suppressed rhEPO-induced extramedullary erythropoiesis and polycythemia in mice, as well as hematocrits and spleen sizes, especially had no effect on white blood cell count. Furthermore, WWQ-131 (75 mg/kg) exhibited stronger therapeutic effects than fedratinib (120 mg/kg) in these two MPN models. Taken together, this study suggests that WWQ-131 will be a promising candidate for the treatment of MPNs.

A Reconfigurable Nanophotonic Heterostructure Engineered by a DNA Origami Switch.

DNA origami has been widely used to construct nanophotonic structures due to its unparallel capability in assembling photonic nanomaterials with nanometer precision. Nevertheless, the majority of fabricated fluorescence-based nanophotonic systems so far operate in the ultraviolet-visible (UV-Vis) region, which are accompanied by limitations of shallow penetration and potential light damage. Herein, we constructed a reconfigurable nanophotonic heterostructure by integrating an upconversion nanoparticle (UCNP) and a gold nanorod (AuNR) on a DNA origami switch (DOS) template. With the unique anti-Stokes luminescence of UCNP whose excitation wavelength is mostly located in the near-infrared (NIR) region, the obtained reconfigurable nanophotonic system can be excited by 980 laser light and generates visible light emission. In our nanophotonic system, the DNA origami template serves as a switch to reversibly tune the optical properties of UCNP. The construction of this nanophotonic heterostructure expands the toolbox of DNA origami-based nanophotonic systems that may hold great potential in optical biosensing and imaging.

Monocytes subtypes from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy.

BACKGROUND: Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion. METHODS: Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL-1ß, IL-17, IL-27, and IFN-γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real-time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions. RESULTS: CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL-1ß, IL-17, IL-27, and IFN-γ, in TPE were much higher than in other pleural effusions. Moreover, CD14+ CD16++ nonclassical subset frequency in TPE was remarkably higher than that in MPE, while CD14++ CD16+ intermediate subset proportion in MPE was found elevated. Furthermore, CX3CL1-CX3CR1 axis-mediated infiltration of nonclassical monocytes in TPE was related to CX3CL1 and IFN-γ expression in TPE. Higher expression of cytokines (IL-1ß, IL-17, IL-27, and IFN-γ) were found in nonclassical monocytes compared with other subsets. Additionally, the proportions of intermediate and nonclassical monocytes in pleural effusion have the power in discriminating tuberculosis from malignant pleural effusion. CONCLUSIONS: CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE.

Recruitment of IL-1ß-producing intermediate monocytes enhanced by C5a contributes to the development of malignant pleural effusion.

BACKGROUND: Monocytes are involved in tumor growth and metastasis, but the distribution of monocyte phenotypes and their role in the development of malignant pleural effusion (MPE) remains unknown. METHODS: A total of 94 MPE patients (76 diagnosed with adenocarcinoma lung cancer and 18 with squamous cell lung cancer) and 102 volunteers for health examination in Xiangya Hospital from December 2016 to December 2019 were included in the study. RESULTS: The distribution of monocyte subtypes identified by the expression of CD14 and CD16 were analyzed by flow cytometry. The proportion of CD14++ CD16+ intermediate monocytes were significantly increased in pleural effusion of MPE patients. The complement system components were assayed by immunohistochemistry and ELISA, and higher expression of the classical and alternative pathways were detected in malignant pleural tissue. Transwell assay further revealed that C5a enhanced the infiltration of intermediate monocytes into the pleural cavity by promoting CCL2 production in pleural mesothelial cells (PMCs). In addition, C5a promoted the secretion of IL-1ß by intermediate monocytes. Furthermore, C5a activated in intermediate monocytes and IL-1ß released after C5a stimulation by monocytes promoted the proliferation, migration, adhesion, and epithelial-to-mesenchymal transition (EMT) of tumor cells, and attenuated tumor cell apoptosis. CONCLUSIONS: C5a, activated by the classical and alternative pathways of the complement system, not only mediated the infiltration of intermediate monocytes by enhancing CCL2 production in PMCs but also induced IL-1ß release from the recruited monocytes in MPE. The consequence of C5a activation and the subsequent IL-1ß overexpression in intermediate monocytes contributed to MPE progression.

A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.

Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma.

GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1-/- asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1 to IRF1 and IRF3 was upregulated in GLCCI1-/- Dex-treated asthmatic mice compared to wild type Dex-treated asthmatic mice. We also found that GLCCI1 knockdown reduced GR and GRIP1 expression but increased IRF1 and IRF3 expression in Beas2B and A549 cells. Additionally, GLCCI1 silencing increased the interactions between GRIP1 with IRF1 and GRIP1 with IRF3, but decreased the recruitment of GRIP1 to GR. These studies support a critical but previously unrecognized effect of GLCCI1 expression on epithelial cells in asthma GC responses by which GLCCI1 deficiency reduces the GR and GRIP1 interaction but competitively enhances the recruitment of GRIP1 to IRF1 and IRF3.

Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

Maternal mortality ratio in Jiangsu Province, China: recent trends and associated factors.

BACKGROUND: In recent years, births to older mothers and multiparous mothers have increased rapidly with the change of birth policy in China. And mothers of advanced age are more likely to have maternal complications and poor birth outcomes. We aimed to estimate the recent trends and underlying risk factors of maternal mortality. METHODS: In this systematic assessment, we used data from the National Maternal and Child Health Routine Reporting System (2013-2018), Jiangsu Provincial Maternal Mortality Surveillance System (2017-2018), the Integrated National Mortality Surveillance System (2018), City Statistical Yearbooks (2018), City Health Statistical Yearbooks (2018). The factors associated with maternal mortality ratio (MMR) were explored using the stepwise regression analysis and cluster analysis. RESULTS: The MMR maintained at low levels between 2013 and 2016 and there was a slight increase in maternal mortality after 2016 in Jiangsu province. With the implementation of the China's universal two child policies, the percentage of multiparous mothers ascended from 34.2% (95% confidence interval (CI) = 34.1-34.3%) in 2013 to 51.4% (95% CI = 51.3-51.6%) in 2018 (beta = 3.88, P < 0.001). Consistently, the percentage of advanced maternal age (≥ 35) increased from 8.4% (95% CI = 8.4-8.5%) in 2013 to 10.4% (95% CI = 10.3-10.4%) in 2018 (beta = 0.50, P = 0.012). And we found that the percentage of multiparous mothers and advanced maternal age among maternal deaths were higher than all pregnant women (P < 0.001). In the stepwise regression analysis, four risk factors were significantly associated with maternal mortality ratio (primary industry of gross domestic product (GDP), rate of delivery in maternal and child health hospital, rate of cesarean section and rate of low birth weight). As the results derived from cluster analysis, the relatively developed regions had lower preventable maternal mortality ratio (43.5% (95% CI = 31.2-56.7%) vs. 62.6% (95% CI = 52.3-72.0%), P = 0.027). CONCLUSIONS: Since the universal two child policy has been associated with changes in health related birth characteristics: women giving birth have been more likely to be multiparous, and more likely to be aged 35 and over. This somewhat magnifies the impact of differences in economic development and obstetric services on MMR. The findings based on prefecture level data suggest that interventions must target economic development, the health system and maternal risk factors in synergy. These approaches will be of great benefit to control or diminish environmental factors associated with preventable deaths and will effectively reduce MMR and narrow the gap among the different regions.

Analysis of pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence.

BACKGROUND: To investigate the changes in pelvic floor electrical physiological parameters in nulliparous women with stress urinary incontinence (SUI). METHODS: A retrospective survey was conducted on 922 women aged 20-40 years who received health examinations at the First Affiliated Hospital of Nanjing Medical University between July 2017 and December 2019. The women were split into two groups: those who had SUI (n=87) and those that did not (n=835). Questionnaires and pelvic floor electrical physiological indexes were collected. RESULTS: The mean age of the group of women with SUI was 29.77 years, while the mean age of the group of women with no SUI was 24.49 years. The body mass indexes (BMI) of the women with SUI were significantly higher than those of the women with no SUI. Importantly, the normal rates of type I and II fibers in the women with SUI were obviously lower than those in the women with no SUI. Moreover, the vaginal dynamic pressure in the women with SUI was significantly lower than in the women with no SUI. The study also found that the incidence of SUI in nulliparous women was higher in those aged 30-40 and that both low-weight and obese women had an increased risk of SUI. Type I and type II muscle fibers were more abnormal in the women with SUI than in those with no SUI. In multivariate logistic regression, the ages, BMIs, and type I fiber indexes of nulliparous women were related to SUI. CONCLUSIONS: Nulliparous women have a higher rate of SUI. Compared to women with no SUI, the possible potential risk factors are age (>30 years), higher BMI, and abnormal type I muscle fiber of the pelvic floor.

Effect of Optimized Irrigation With Photon-Induced Photoacoustic Streaming on Smear Layer Removal, Dentin Microhardness, Attachment Morphology, and Survival of the Stem Cells of Apical Papilla.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the effect of optimized irrigation with photon-induced photoacoustic streaming (PIPS) activation of different irrigants (distilled water or ethylenediaminetetraacetic acid [EDTA]) on smear layer removal, dentin microhardness, attachment morphology, and survival of stem cells of the apical papilla (SCAP) in an organotypic root canal model. STUDY DESIGN/MATERIALS AND METHODS: A total of 144 standardized root segments were randomly allocated into 6 groups for irrigation: (i) NaOCl group, (ii) NaOCl + EDTA group, (iii) NaOCl + PIPS (distilled water) group, (iv) NaOCl + PIPS (EDTA) group, (v) NaOCl + EDTA + PIPS (distilled water) group, and (vi) NaOCl + EDTA + PIPS (EDTA) group. Each group was divided into four subgroups for assessment: (i) dentin cleanliness; (ii) dentin microhardness; (iii) cell attachment morphology; and (iv) viable SCAP quantification. RESULTS: Compared with the control groups, the NaOCl + EDTA + PIPS (EDTA) group showed higher efficiency in smear layer removal and in increasing SCAP viability with more stretched cellular morphology. There were no statistically significant differences in either smear layer removal effect, dentin microhardness, attachment morphology, or survival of SCAP among the other groups when optimized with PIPS (distilled water or EDTA) (P > 0.05). CONCLUSIONS: Our findings indicated that irrigation optimized with PIPS activation of EDTA for 40 seconds was conducive to smear layer removal without additional dentin microhardness decrease. Additionally, this irrigation created more cell-friendly dentin conditioning than other approaches, which was beneficial for the attachment and survival of SCAP. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Modular Reconfigurable DNA Origami: From Two-Dimensional to Three-Dimensional Structures.

DNA origami enables the manipulation of objects at nanoscale, and demonstrates unprecedented versatility for fabricating both static and dynamic nanostructures. In this work, we introduce a new strategy for transferring modular reconfigurable DNA nanostructures from two-dimensional to three-dimensional. A 2D DNA sheet could be modularized into connected parts (e.g., two, three, and four parts in this work), which can be independently transformed between two conformations with a few DNA "trigger" strands. More interestingly, the transformation of the connected 2D modules can lead to the controlled, resettable structural conversion of a 2D sheet to a 3D architecture, due to the constraints induced by the connections between the 2D modules. This new approach can provide an efficient mean for constructing programmable, higher-order, and complex DNA objects, as well as sophisticated dynamic substrates for various applications.