Visible-light-driven asymmetric aldol reaction of ketones and glycinates via synergistic Lewis acid/photoredox catalysis.

Visible-light-driven direct asymmetric α-C(sp3)-H bond functionalization of glycinate provides a direct and efficient route for the synthesis of diverse optically enriched α-amino acid derivatives. However, asymmetric coupling between glycinate radical species and ketones faces significant challenges, including competitive pathways, mutable intermediates, as well as congested stereogenic centers. Herein, we disclose the first example for the asymmetric photocatalytic synthesis of a diverse array of ß-diaryl-ß-hydroxy-α-amino acetate derivatives from glycinates and heteroaryl ketones through the synergistic catalysis of achiral iridium photoredox catalyst and chiral lanthanide Lewis acid catalysts. The enantioselective radical addition pathway is supported by spectroscopic experiments, control experiments and DFT calculations.

Asymmetric catalytic concise synthesis of 3-(3-indolomethyl)-oxindoles for the construction of trigolute analogs.

Asymmetric synthesis of 3-(3-indolomethyl)oxindoles through the addition of indole-substituted enolized ketoesters to 3-bromo-3-substituted oxindoles has been achieved using a N,N'-dioxide/Ho(III) complex. A number of 3-(3-indolomethyl)oxindoles, which may possess biological activity, were obtained in good yields with high diastereo- and enantioselectivities (up to 97% yield, >19 : 1 dr, 98% ee). Furthermore, time-dependent reversal of diastereoselectivity enabled access to optically active diastereomers. The product followed by facile transformations gave a new route into trigolute analogs.

Novel fabrication of anti-VEGF drug ranibizumab loaded PLGA/PLA co-polymeric nanomicelles for long-acting intraocular delivery in the treatment of age-related macular degeneration therapy.

Age associated macular degeneration is the 3rd primary cause of blind fundus diseases globally. A reliable and long-lasting method of intraocular drug delivery is still needed. Herein, this study was aim to develop the novel fabrication of ranibizumab loaded co-polymeric nanomicelles (Rabz-CP-NMs) for AMD. The CMC of co-polymeric nanomicelles was determined to be low, at 6.2 µg/ml. The ring copolymerization method was employed to fabricate the NMs and characterize via FTIR, XRD, TEM, DLS and Zeta potential. Rabz-CP-NMs was spherical shape with 10-50 nm in size. Stable and prolonged drug release was achieved with the Rabz from CP-NMs at 48 h. D407 and ARPE19 ocular cell lines showed dose-dependent cell viability with Rabz-CP-NMs. The Rabz-CP-NMs also had less toxicity, higher uptake, lower cell death and prolonged VEGF-A inhibition, as shown by cytoviability assay. Thus, Rabz-CP-NMs were safe for ocular use, suggesting that could be used to improve intraocular AMD treatment.

The Association of Dietary Diversity with Hyperuricemia among Community Inhabitants in Shanghai, China: A Prospective Research.

Hyperuricemia, a major worldwide burden on public hygiene, is closely connected with dietary habits. However, few studies have evaluated the association of dietary diversity with hyperuricemia. To preliminarily reveal the status of a diversified diet in preventing hyperuricemia based on a neighborhood-based, massive-scale cohort in China, a total of 43,493 participants aged 20-74 years old, with no history of hyperuricemia at baseline, were enrolled in the research from April 2016 to December 2019. The Dietary Diversity Score (DDS) was utilized to evaluate the dietary variety and split the participants into the low-, medium-, and high-DDS groups. Information on participants was connected to regional health information systems that acquired data on hyperuricemia instances up to 28 February 2023. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed by Cox proportional hazards models. Restricted cubic splines (RCS) were implemented to analyze dose-response correlation. A total of 1460 individuals with newly diagnosed hyperuricemia were observed over a median follow-up period of 5.59 years. Compared to the low-DDS group, HRs for the medium- and high-DDS groups were 0.87 (95% CI 0.76-0.99) and 0.80 (95% CI 0.70-0.91) in the fully adjusted model, respectively. The risk of hyperuricemia incidence was reduced by 5% for each 1 unit of DDS increase. A linear correlation of DDS with hyperuricemia emerged and further revealed that the intake of 8-10 broad categories of food could decrease the incidence of hyperuricemia. Our results validate the dietary principle of "food diversification" recommended in guidelines. Conclusions should be applied with caution considering the paucity of related evidence in additional nations.

Anti-Toxoplasma gondii effects of XYP1-derived peptides and regulatory mechanisms of XYP1.

BACKGROUND: Toxoplasmosis, caused by Toxoplasma gondii , poses serious health issues for humans and animals. Individuals with impaired immune systems are more susceptible to severe toxoplasmosis. Pregnant women infected by T. gondii can face the possibility of birth defects and miscarriages. While pyrimethamine and sulfadiazine are commonly used drugs in clinical practice, concerns over their side effects and resistance are on the rise. A spider peptide XYP1 isolated from Lycosa coelestis had potent anti-T. gondii effects, but it had a high synthesis cost and strong cytotoxicity. METHODS: This study intended to modify XYP1 for producing derived peptides via amino acid truncation and substitution. The anti-T. gondii effect was evaluated by trypan blue staining assay and killing experiment of RH strain tachyzoites. The CCK8 and hemolysis assays were used to compare their safeties. The morphological changes of T. gondii were observed by scanning electron microscope and transmission electron microscope. In addition, the mechanism of XYP1 against T. gondii through RNA-sequencing was further explored. RESULTS: In vivo and in vitro experiments revealed that XYP1-18 and XYP1-18-1 had excellent anti-T. gondii activity with lower cytotoxicity and hemolysis activity than XYP1. XYP1, XYP1-18, and XYP1-18-1 were able to disrupt the surface membrane integrity of T. gondii tachyzoites, forming pores and causing the disruption of organelles. Furthermore, RNA-sequencing analysis indicated that XYP1 could stimulate the host immune response to effectively eliminate T. gondii and lessen the host's inflammatory reaction. CONCLUSIONS: XYP1-18 had lower cytotoxicity and hemolysis activity than XYP1, as well as significantly extending the survival time of the mice. XYP1 played a role in host inflammation and immune responses, revealing its potential mechanism. Our research provided valuable insights into the development and application of peptide-based drugs, offering novel strategies and directions for treating toxoplasmosis.

Engineering of Bioresorbable Polymers for Tissue Engineering and Drug Delivery Applications.

Herein, the recent advances in the development of resorbable polymeric-based biomaterials, their geometrical forms, resorption mechanisms, and their capabilities in various biomedical applications are critically reviewed. A comprehensive discussion of the engineering approaches for the fabrication of polymeric resorbable scaffolds for tissue engineering, drug delivery, surgical, cardiological, aesthetical, dental and cardiovascular applications, are also explained. Furthermore, to understand the internal structures of resorbable scaffolds, representative studies of their evaluation by medical imaging techniques, e.g., cardiac computer tomography, are succinctly highlighted. This approach provides crucial clinical insights which help to improve the materials' suitable and viable characteristics for them to meet the highly restrictive medical requirements. Finally, the aspects of the legal regulations and the associated challenges in translating research into desirable clinical and marketable materials of polymeric-based formulations, are presented.

Predicting BRCA mutation and stratifying targeted therapy response using multimodal learning: a multicenter study.

BACKGROUND: The status of BRCA1/2 genes plays a crucial role in the treatment decision-making process for multiple cancer types. However, due to high costs and limited resources, a demand for BRCA1/2 genetic testing among patients is currently unmet. Notably, not all patients with BRCA1/2 mutations achieve favorable outcomes with poly (ADP-ribose) polymerase inhibitors (PARPi), indicating the necessity for risk stratification. In this study, we aimed to develop and validate a multimodal model for predicting BRCA1/2 gene status and prognosis with PARPi treatment. METHODS: We included 1695 slides from 1417 patients with ovarian, breast, prostate, and pancreatic cancers across three independent cohorts. Using a self-attention mechanism, we constructed a multi-instance attention model (MIAM) to detect BRCA1/2 gene status from hematoxylin and eosin (H&E) pathological images. We further combined tissue features from the MIAM model, cell features, and clinical factors (the MIAM-C model) to predict BRCA1/2 mutations and progression-free survival (PFS) with PARPi therapy. Model performance was evaluated using area under the curve (AUC) and Kaplan-Meier analysis. Morphological features contributing to MIAM-C were analyzed for interpretability. RESULTS: Across the four cancer types, MIAM-C outperformed the deep learning-based MIAM in identifying the BRCA1/2 genotype. Interpretability analysis revealed that high-attention regions included high-grade tumors and lymphocytic infiltration, which correlated with BRCA1/2 mutations. Notably, high lymphocyte ratios appeared characteristic of BRCA1/2 mutations. Furthermore, MIAM-C predicted PARPi therapy response (log-rank p < 0.05) and served as an independent prognostic factor for patients with BRCA1/2-mutant ovarian cancer (p < 0.05, hazard ratio:0.4, 95% confidence interval: 0.16-0.99). CONCLUSIONS: The MIAM-C model accurately detected BRCA1/2 gene status and effectively stratified prognosis for patients with BRCA1/2 mutations.

Exploring the MRI and Clinical Features of P53-Mutated Hepatocellular Carcinoma.

Purpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients. Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student's t test, χ2 test, and multivariable regression analysis. Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson-Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC. Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.

Asymmetric Catalytic Synthesis of Allylic Sulfenamides from Vinyl α-Diazo Compounds by a Rearrangement Route.

The asymmetric rearrangement of allylic sulfilimines is an effective route to synthetic attractive targets such as allylic sulfenamides and others. The current methods are limited to chirality transfer from chiral allylic sulfilimine precursors. Herein, we report a general and fundamentally new rearrangement route accessing optically enriched allylic sulfenamides and their derivatives. The process involves a S-alkylation and an unusual S-to-N rearrangement step. The chiral nickel complex enables the transformation of a broad scope of sulfenamides and vinyl α-diazo pyrazoleamides under mild conditions. Various allylic sulfenamides have been synthesized with excellent γ-regioselectivity and enantioselectivity, which can be efficiently converted to sulfinamide and 4-aminobutenoic acid derivatives. In addition, DFT calculations demonstrate the connection between the spin state and conformation of nickel vinyl carbenoid, as well as an unknown rearrangement process.

Nanoparticles constructed from natural polyphenols are used in acute kidney injury.

Acute kidney injury (AKI) is a severe clinical syndrome characterized by rapid deterioration of renal function caused by a variety of pathogeneses. Natural polyphenols have been considered to have potential in the treatment of AKI due to their powerful antioxidant and anti-inflammatory activities, but their low bioavailability in vivo limits their efficacy. Polyphenol nanoparticles based on a nano-delivery system show good effects in reducing kidney injury, improving renal function and promoting renal tissue repair, and brings new hope and possibility for the treatment of AKI. This review provides an overview of the common characteristics, treatments, and associated adverse effects of AKI. The classification and bioavailability of polyphenols as well as their therapeutic role in AKI and potential possible effects are outlined. The potential therapeutic effects of polyphenol-based nanoparticles on AKI and the underlying mechanisms are discussed.

Vaginal dinoprostone vs Foley catheter for induction of labor at term with an unfavorable cervix: an open-label randomized controlled trial.

BACKGROUND: Induction of labor (IOL) with mechanical methods or pharmacological agents is used in about 20% to 30% of all pregnant women. We specialized in comparing the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix with adequate samples. OBJECTIVE: To compare the effectiveness and safety of dinoprostone vs transcervical Foley catheter for IOL in term pregnant women with an unfavorable cervix. STUDY DESIGN: This is a parallel, open-label randomized controlled trial in two maternal centers in Shanghai, China between October 2019 and July 2022. Women with a singleton pregnancy in cephalic presentation at term and an unfavorable cervix (Bishop score <6) scheduled for IOL were eligible. A total of 1860 women were randomly allocated to cervical ripening with either a dinoprostone vaginal insert (10 mg) or a 60 cc Foley catheter for up to 24 hours. The primary outcomes were vaginal delivery rate and time to vaginal delivery. Secondary outcomes included time to delivery and maternal and neonatal morbidity. Analysis was done from an intention-to-treat perspective. The trial was registered with the China trial registry (CTR2000038435). RESULTS: The vaginal birth rates were 72.8% (677/930) vs 69.9% (650/930) in vaginal dinoprostone and Foley catheter, respectively (aRR 1.04, 95% confidence interval [CI] 0.98-1.10, risk difference: 0.03). Time to vaginal delivery was not significantly different between the two groups (sub-distribution hazard ratio 1.11, 95% CI 0.99-1.24). Vaginal dinoprostone was more likely complicated with hyperstimulation with fetal heart rate changes (5.8% vs 2.8%, aRR 2.09, 95% CI 1.32-3.31) and placenta abruption (0.9% vs 0.1%, aRR: 8.04, 95% CI 1.01-64.15), while Foley catheter was more likely complicated with suspected intrapartum infection (5.1% vs 8.2%, aRR: 0.62, 95% CI 0.44-0.88) and postpartum infection (1.4% vs 3.7%, aRR: 0.38, 95% CI 0.20-0.72). The composite of poor neonatal outcomes was not significantly different between the two groups (4.5% vs 3.8%, aRR 1.21, 95% CI 0.78-1.88), while more neonatal asphyxia occurred in the dinoprostone group (1.2% vs 0.2%, aRR 5.39, 95% CI 1.22-23.92). In a subgroup analysis, vaginal dinoprostone decreased vaginal birth rate slightly in multiparous women (90.6% vs 97.0%, aRR 0.93, 95% CI 0.88-0.99). CONCLUSIONS: In term pregnant women with an unfavorable cervix, IOL with vaginal dinoprostone or Foley catheter has similar effectiveness. Foley catheter leads to better safety for neonates, while it may result in a higher risk of maternal infection. Furthermore, Foley catheter should be preferred in multiparous women.

Discovery of a Covalent Inhibitor of Pro-Caspase-1 Zymogen Blocking NLRP3 Inflammasome Activation and Pyroptosis.

Caspase-1 plays a central role in innate immunity, as its activation by inflammasomes induces the production of proinflammatory cytokines and pyroptosis. However, specific inhibition of the enzymatic activity of this protease is not effective in suppressing inflammation, owing to its enzyme-independent function. Herein, we identified a cyclohexenyl isothiocyanate compound (CIB-1476) that potently inhibited caspase-1 activity and suppressed the assembly and activation of the NLRP3 inflammasome and gasdermin-D-mediated pyroptosis. Mechanistically, CIB-1476 directly targeted pro-caspase-1 as an irreversible covalent inhibitor by binding to Cys285 and Cys397, resulting in more durable anti-inflammatory effects in the suppression of enzyme-dependent IL-1ß production and enzyme-independent nuclear factor κB activation. Chemoproteomic profiling demonstrated the engagement of CIB-1476 with caspase-1. CIB-1476 showed potent therapeutic effects by suppressing inflammasome activation in mice, which was abolished in Casp1-/- mice. These results warrant further development of CIB-1476 along with its analogues as a novel strategy for caspase-1 inhibitors.

Correction: Asymmetric catalytic [1,3]- or [3,3]-sigmatropic rearrangement of 3-allyloxy-4H-chromenones and their analogues.

[This corrects the article DOI: 10.1039/D4SC02201G.].

Effect of type 2 diabetes on biochemical markers of bone metabolism: a meta-analysis.

Objective: This meta-analysis aims to examine differences in biochemical markers of bone metabolism between individuals with type 2 diabetes (T2DM) and non-T2DM control groups. Materials and methods: Two independent evaluators searched five databases: PubMed, EMBASE, EBSCOhost, Web of Science, and the Cochrane Library. We aimed to identify observational studies investigating the impact of T2DM on biochemical markers of bone metabolism. Literature retrieval covered the period from the establishment of the databases up to November 2022. Studies were included if they assessed differences in biochemical markers of bone metabolism between T2DM patients and non-T2DM control groups using cross-sectional, cohort, or case-control study designs. Results: Fourteen studies were included in the analysis, comprising 12 cross-sectional studies and 2 cohort studies. Compared to the non-T2DM control group, T2DM patients showed reduced levels of Osteocalcin and P1NP, which are markers of bone formation. Conversely, levels of Alkaline phosphatase and Bone-specific alkaline phosphatase, other bone formation markers, increased. The bone resorption marker CTX showed decreased levels, while TRACP showed no significant difference. Conclusion: In individuals with T2DM, most bone turnover markers indicated a reduced rate of bone turnover. This reduction can lead to increased bone fragility despite higher bone mineral density, potentially increasing the risk of osteoporosis.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php? identifier CRD42022366430.

Hippocampal subfield morphology from first episodes of bipolar disorder type II and major depressive disorder in a drug naïve Chinese cohort.

Introduction: Symptoms during the onset of major depressive disorder [MDD] and bipolar disorder type II [BD-II] are similar. The difference of hippocampus subregion could be a biological marker to distinguish MDD from BD-II. Methods: We recruited 61 drug-naïve patients with a first-episode MDD and BD-II episode and 30 healthy controls (HC) to participate in a magnetic resonance imaging [MRI] study. We built a general linear model (one-way analysis of covariance) with 22 hippocampal subfields and two total hippocampal volumes as dependent variables, and the diagnosis of MDD, BD-II, and HC as independent variables. We performed pair-wise comparisons of hippocampal subfield volumes between MDD and HC, BD-II and MDD, BD-II and HC with post hoc for primary analysis. Results: We identified three regions that differed significantly in size between patients and controls. The left hippocampal fissure, the hippocampal-amygdaloid transition area (HATA), and the right subiculum body were all significantly larger in patients with MDD compared with the HC. In the onset of first-episode of MDD, the hippocampal volume increased significantly, especially on the left side comparing to HC. However, we found differences between MDD and BD-II were not statistically significant. The volume of the left HATA and right subiculum body in BD-II was larger. Conclusions: The sample size of this study is relatively small, as it is a cross-sectional comparative study. In both MDD and BD-II groups, the volume of more left subregions appeared to increase. The left subregions were severely injured in the development of depressive disorder.

Attenuated frontotemporal brain activation during cognitive tasks is associated with lower succinate dehydrogenase protein levels in patients with major depressive disorder.

BACKGROUND: Previous studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism. METHODS: Fifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Activation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD. CONCLUSIONS: MDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD. LIMITATIONS: The sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.

Severity of depressive and anxious symptoms and its association with birth outcomes among pregnant women during the COVID-19 pandemic: a prospective case-control study.

AIM: Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022. METHODS: The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression. FINDINGS: Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods. CONCLUSION: The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.

Diagnostic value of D-dimer to fibrinogen ratio for pulmonary embolism in postpartum women.

BACKGROUND: Pulmonary embolism is a common disease associated with high mortality and morbidity. Diagnosing pulmonary embolism is challenging due to diverse clinical presentations and the lack of specific biomarkers. The study aimed to investigate the diagnostic value on pulmonary embolism for postpartum women by D-dimer to fibrinogen ratio, and it combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio. METHODS: A total of 537 women with suspected pulmonary embolism were selected as the research subjects from the Shanghai First Maternity and Infant Hospital between 1 January 2019 and 31 October 2022. The D-dimer to fibrinogen ratio and it combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio were applied to evaluate the clinical probability of pulmonary embolism, and the positive predictive value of both scores were calculated using computed tomography pulmonary arteriography as a gold standard. The diagnostic value of D-dimer to fibrinogen ratio, combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio was evaluated by the area under the curve, sensitivity, specificity, and other indicators in the receiver operator characteristic curve. RESULTS: Among the 502 women included for analysis, 194 (38.65%) were definitely diagnosed as pulmonary embolism. The positive predictive values of D-dimer to fibrinogen ratio and it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 70.1%, 50.5%, and 56.5%, respectively in the postpartum women, the area under the curve for the D-dimer to fibrinogen ratio and it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 0.606 (95%CI: 0.562-0.650), 0.624 (95%CI: 0.575-0.673), and 0.639 (95%CI: 0.592-0.686), respectively. The negative predictive values of D-dimer to fibrinogen ratio, it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 50.5%, 70.1%, and 69.8%, respectively. CONCLUSION: The diagnostic value of the D-dimer to fibrinogen ratio was higher than the D-dimer for the postpartum women with suspected pulmonary embolism. The combination of either the neutrophil-to-lymphocyte ratio or the platelet-to-lymphocyte ratio with D-dimer to fibrinogen ratio is an appropriate strategy to rule out pulmonary embolism.

Accurately Computing the Interacted Volume of Molecules over Their 3D Mesh Models.

For quickly predicting the rational arrangement of catalysts and substrates, we previously proposed a method to calculate the interacted volumes of molecules over their 3D point cloud models. However, the nonuniform density in molecular point clouds may lead to incomplete contours in some slices, reducing the accuracy of the previous method. In this paper, we propose a two-step method for more accurately computing molecular interacted volumes. First, by employing a prematched mesh slicing method, we layer the 3D triangular mesh models of the electrostatic potential isosurfaces of two molecules globally, transforming the volume calculation into finding the intersecting areas in each layer. Next, by subdividing polygonal edges, we accurately identify intersecting parts within each layer, ensuring precise calculation of interacted volumes. In addition, we present a concise overview for computing intersecting areas in cases of multiple contour intersections and for improving computational efficiency by incorporating bounding boxes at three stages. Experimental results demonstrate that our method maintains high accuracy in different experimental data sets, with an average relative error of 0.16%. On the same experimental setup, our average relative error is 0.07%, which is lower than the previous algorithm's 1.73%, improving the accuracy and stability in calculating interacted volumes.

Visible-Light-Promoted Enantioselective Acylation and Alkylation of Aldimines Enabled by 9-Fluorenone Electron-Shuttle Catalysis.

Chiral acyclic α-tertiary amino ketones are widely present in various natural products and pharmaceuticals; however, the direct synthesis of this pharmacophore through a robust strategy still presents significant challenges. The emerging photocatalysis provides a powerful approach to construct chemical bonds that are difficult to form via a traditional two-electron pathway. Herein, we developed visible-light-induced chiral Lewis acid-catalyzed highly enantioselective acylation/alkylation of aldimines enabled by cooperative FLN (9-fluorenone) electron-shuttle catalysis via radical addition. An array of α-tertiary amino ketones, ß-amino alcohols, and chiral amines were achieved with high yields and good to excellent stereocontrol (87 examples, up to 84% yield, 96% ee). These products can be easily transformed into valuable and bioactive skeletons. Extensive control experiments, detailed mechanism studies, and density functional theory calculations elucidated the reaction process and highlighted the crucial role played by FLN.