Causal Relationships Between Leukocyte Subsets and Adverse Fetal Outcomes: A Mendelian Randomization Study.

The tolerance and dynamic regulation of the maternal immune system during pregnancy are pivotal for ensuring fetal health. Immune cell subsets play a complex and crucial role in this process, closely linked to the neonatal health status. Despite recognizing the significance of dysregulation in the quantity and activity of immune cells in neonatal disease occurrence, their specific roles remain elusive, resulting in a dearth of clinically viable interventions for immune-mediated neonatal diseases.

SiO Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model.

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO -induced cardiac injury using a mouse model.

Methods: Male C57BL/6 mice were intratracheally instilled with SiO to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis.

A Functional Switch Between Asperfumene and Fusicoccadiene Synthase and Entrance to Asperfumene Biosynthesis through a Vicinal Deprotonation-Reprotonation Process.

The diterpene synthase AfAS was identified from Aspergillus fumigatiaffinis. Its amino acid sequence and-according to a structural model-active site architecture are highly similar to those of the fusicocca-2,10(14)-diene synthase PaFS, but AfAS produces a structurally much more complex diterpene with a novel 6-5-5-5 tetracyclic skeleton called asperfumene. The cyclisation mechanism of AfAS was elucidated through isotopic labelling experiments and DFT calculations.

Functional and structural dissection of glycosyltransferases underlying the glycodiversity of wolfberry-derived bioactive ingredients lycibarbarspermidines.

Lycibarbarspermidines are unusual phenolamide glycosides characterized by a dicaffeoylspermidine core with multiple glycosyl substitutions, and serve as a major class of bioactive ingredients in the wolfberry. So far, little is known about the enzymatic basis of the glycosylation of phenolamides including dicaffeoylspermidine. Here, we identify five lycibarbarspermidine glycosyltransferases, LbUGT1-5, which are the first phenolamide-type glycosyltransferases and catalyze regioselective glycosylation of dicaffeoylspermidines to form structurally diverse lycibarbarspermidines in wolfberry.

Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived from and Its Bioinspired Total Synthesis.

, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from , namely falcarinphthalides A and B ( and ), which contains two fragments, (3,8)-falcarindiol () and ()-ligustilide (). Falcarinphthalides A and B ( and ) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated.

Gestational diabetes mellitus aggravates adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy.

Purpose: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) with gestational diabetes mellitus (GDM) on perinatal outcomes and establish a prediction model of adverse perinatal outcomes in women with ICP.

Methods: This multicenter retrospective cohort study included the clinical data of 2,178 pregnant women with ICP, including 1,788 women with ICP and 390 co-occurrence ICP and GDM. The data of all subjects were collected from hospital electronic medical records.

Novel ligustilide derivatives target quorum sensing system LasR/LasB and relieve inflammatory response against Pseudomonas aeruginosa infection.

The increasing antibiotic resistance driven by Pseudomonas aeruginosa typically leads to uncontrolled and persistent inflammatory damage, which is primarily attributed to the virulence and biofilms produced by the bacteria. Herein, we present a novel anti-infective drug strategy designed to inhibit the bacterial quorum sensing system, thereby attenuating P. aeruginosa virulence, and modulating inflammation from drug-resistant bacterial infections.

Oxidative aromatization mechanism of ligustilide.

The aromatization mechanisms of ligustilide (1), a versatile monomeric phthalide, were investigated. DFT calculations combined with control experiments prove that the aromatization could result from direct oxidation by triplet oxygen in mild conditions with no catalyst, which is generally thought to be difficult. Moreover, it is predicted that the aromatization could rapidly clear away the harmful-to-organism singlet oxygen, which may be relevant to the general antioxidation activity of phthalides, providing a new point of view to understand the bioactivity from chemical reaction.

Identification of highly reliable risk genes for Alzheimer's disease through joint-tissue integrative analysis.

Numerous genetic variants associated with Alzheimer's disease (AD) have been identified through genome-wide association studies (GWAS), but their interpretation is hindered by the strong linkage disequilibrium (LD) among the variants, making it difficult to identify the causal variants directly. To address this issue, the transcriptome-wide association study (TWAS) was employed to infer the association between gene expression and a trait at the genetic level using expression quantitative trait locus (eQTL) cohorts. In this study, we applied the TWAS theory and utilized the improved Joint-Tissue Imputation (JTI) approach and Mendelian Randomization (MR) framework (MR-JTI) to identify potential AD-associated genes.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities.

[HADHA Inhibits the Migration and Invasion of HTR-8/SVneo Cells by Regulating PI3K/AKT Signaling Pathway].

Objective: To explore the effects of hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) on the migration and invasion of HTR-8/SVneo cells, a human trophoblast cell line, and its potential mechanism of action.

Methods: Immunofluorescence staining was done to evaluate the expression levels of HADHA in samples of normal villi and recurrent spontaneous abortion (RSA) villi at 6-8 weeks. Lentiviral infection system was used to construct stable HTR-8/SVneo cell lines with overexpression and knockdown.

Home Quarantine: A Double-Edged Sword During COVID-19 Pandemic for Hypertensive Disorders of Pregnancy and the Related Complications.

Object: COVID-19 pandemic and worldwide quarantine seriously affected the physical and mental health of the general public. Our study aimed to investigate the effects of the COVID-19 quarantine on pregnancy outcomes among pregnant women with hypertensive disorders of pregnancy (HDP).

Methods: This single-center retrospective cohort study collected complete clinical data of HDP patients with a history of home quarantine in The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) in 2020 as well as the patients without home quarantine in 2018 and 2019.

The Oxidation Cascade of a Rare Multifunctional P450 Enzyme Involved in Asperterpenoid A Biosynthesis.

The cytochrome P450 enzymes (P450s or CYPs) are heme-containing enzymes which catalyze a wide range of oxidation reactions in nature. In our previous study, a rare multifunctional P450 AstB was found, which can dually oxidize two methyl groups (C-19 and C-21) of preasperterpenoid A to asperterpenoid A with 3-carboxyl and 11-hydroxymethyl groups. However, the oxidation order of C-19 and C-21 catalyzed by AstB is unclear.

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875.

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations.

THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia.

Preeclampsia is a pregnancy complication which threatens the survival of mothers and fetuses. It originates from abnormal placentation, especially insufficient fusion of the cytotrophoblast cells to form the syncytiotrophoblast. In this study, we found that THBS1, a matricellular protein that mediates cell-to-cell and cell-to-matrix interactions, is downregulated during the fusion of primary cytotrophoblast and BeWo cells, but upregulated in the placenta of pregnancies complicated by preeclampsia.

Appropriate expression of P57kip2 drives trophoblast fusion via cell cycle arrest.

The syncytiotrophoblast, derived from cytotrophoblast fusion, is responsible for maternal-fetal exchanges, secretion of pregnancy-related hormones, and fetal defense against pathogens. Inadequate cytotrophoblast fusion can lead to pregnancy disorders, such as preeclampsia and fetal growth restriction. However, little is known about the mechanism of cytotrophoblast fusion in both physiological and pathological pregnancy conditions.

4-Hydroxy Pyridones from Heterologous Expression and Cultivation of the Native Host.

4-Hydroxy pyridones are a class of fungi-derived polyketide-nonribosomal peptide products featuring a core of 4-hydroxy-2-pyridone which have a wide range of biological activities. Genome mining of in-house strains using polyketide synthase-nonribosomal peptide synthase as a query identified an endophyte sp. 49Y, which possesses a potential 4-hydroxy pyridone biosynthetic gene cluster.

Biocompatibility and Improved Compression Strength of Reinforced Keratin/Hydroxyapatite Scaffold.

A rapid freezing/lyophilizing/reinforcing process is suggested to fabricate reinforced keratin/hydroxyapatite (HA) scaffold with improved mechanical property and biocompatibility for tissue engineering. The keratin, extracted from human hair, and HA mixture were rapidly frozen with liquid nitrogen and then lyophilized to prepare keratin/HA laminar scaffold. The scaffold was then immersed in PBS for reinforcement treatment, and followed by a second lyophilization to prepare the reinforced keratin/HA scaffold.

Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors.

Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly selective Aurora A inhibitors is difficult because Aurora A and B share high homology and differ only by three residues in their ATP-binding pockets.

Catalytic promiscuity of the non-native FPP substrate in the TEAS enzyme: non-negligible flexibility of the carbocation intermediate.

The TEAS, one of the sesquiterpene cyclases (FPPC), shows enzyme promiscuity that can effectively catalyze both the natural substrate (trans,trans)-FPP and the non-native (cis,trans)-FPP substrate to generate diverse products/byproducts. So far, the catalytic mechanism of the promiscuous substrate is still unclear. In this work, QM(DFT)/MM MD simulations were employed to illuminate the predominant 1,6-closure pathway reaction mechanism for the non-native substrate (cis,trans)-FPP, while the 1,10-closure pathway is the major reaction for the native substrate.

A square-planar nickel dithiolate complex as an efficient molecular catalyst for the electro- and photoreduction of protons.

A square-planar nickel(ii) dithiolate complex is an active molecular catalyst for both photoreduction of protons from water with a turnover number (>1500) and electroreduction of protons from weakly acidic solutions with remarkable turnover frequencies (5575 s at -1.92 V and 1441 s at -1.61 V vs.

Protective effects of oleanolic acid on oxidative stress and the expression of cytokines and collagen by the AKT/NF‑κB pathway in silicotic rats.

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to have several benefits and medicinal properties. However, its protective effects against silica‑induced lung injury and fibrosis remain to be elucidated. The aim of the present study was to investigate the effects of OA on oxidative stress, and the expression of cytokines and collagen in silicotic rats.