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Rhodium-catalyzed regio- and stereoselective three-component carboamidation of 1,3-enynes has been realized using indoles and dioxazolones as the functionalizing reagents. A wide range of multi-substituted skipped 1,4-dienes have been constructed in good yields and excellent stereoselectivity. The stereoselectivity is under substrate control. 1,3-Enynes bearing a relatively bulky alkyne terminus reacted with Z-selectivity. In contrast, a sterically less hindered alkyne terminus tends to predominantly give the E-configured skipped diene. [ABSTRACT FROM AUTHOR]

C−H bond activation has been established as an attractive strategy to access axially chiral biaryls, and the most straightforward method is direct C−H arylation of arenes. However, the arylating source has been limited to several classes of reactive and bulky reagents. Reported herein is rhodium‐catalyzed 1:2 coupling of diarylphosphinic amides and diarylacetylenes for enantio‐ and diastereoselective construction of biaryls with both central and axial chirality. This twofold C−H activation reaction stays contrast to the previously explored Miura–Satoh type 1:2 coupling of arenes and alkynes in terms of chemoselectivity and proceeded under mild conditions with the alkyne acting as a rare arylating reagent. Both C−H activation events are stereo‐determining and are under catalyst control, with the 2nd C−H activation being diastereo‐determining in a remote fashion. Analysis of the stereochemistry of the major and side products suggests moderate enantioselectivity of the initial C−H activation–desymmetrization process. However, the minor (R) rhodium vinyl intermediate is consumed more readily in undesired protonolysis, eventually resulting in high enantio‐ and diastereoselectivity of the major product. [ABSTRACT FROM AUTHOR]

C−H bond activation has been established as an attractive strategy to access axially chiral biaryls, and the most straightforward method is direct C−H arylation of arenes. However, the arylating source has been limited to several classes of reactive and bulky reagents. Reported herein is rhodium‐catalyzed 1:2 coupling of diarylphosphinic amides and diarylacetylenes for enantio‐ and diastereoselective construction of biaryls with both central and axial chirality. This twofold C−H activation reaction stays contrast to the previously explored Miura–Satoh type 1:2 coupling of arenes and alkynes in terms of chemoselectivity and proceeded under mild conditions with the alkyne acting as a rare arylating reagent. Both C−H activation events are stereo‐determining and are under catalyst control, with the 2nd C−H activation being diastereo‐determining in a remote fashion. Analysis of the stereochemistry of the major and side products suggests moderate enantioselectivity of the initial C−H activation–desymmetrization process. However, the minor (R) rhodium vinyl intermediate is consumed more readily in undesired protonolysis, eventually resulting in high enantio‐ and diastereoselectivity of the major product. [ABSTRACT FROM AUTHOR]

Rhodium(III)-catalyzed C–C coupling of heteroarenes and fluorinated α-diazo diketones has been realized for the facile synthesis of 3-arylchromones. The reaction proceeds via chelation-assisted C–H activation, carbene insertion, and uncatalyzed intramolecular nucleophilic aromatic substitution, with C–F cleavage being accommodated in the nucleophilic aromatic substitution step. Three classes of heteroarenes have been defined with decent functional group tolerance. [ABSTRACT FROM AUTHOR]

Rhodium(III)-catalyzed mild and oxidative [4+1] spiroannulation has been realized via C–H activation of oximes and benzoic acids with 1-diazonaphthelen-2(1H)-ones as coupling reagents. This transformation integrates C–H activation and dearomatization and provides a direct approach to spirocyclic isoindole N-oxides and isobenzofuranones with functional group tolerance. [ABSTRACT FROM AUTHOR]

Axial‐to‐central chirality transfer is an important strategy to construct chiral centers, where the axially chiral reagents are mostly limited to atropomerically stable ones. Reported herein is a RhIII‐catalyzed enantioselective spiroannulative synthesis of nitrones. The coupling proceeds via C−H arylation to give an atropomerically metastable biaryl, followed by intramolecular dearomative trapping under oxidative conditions with high degree of chirality transfer. [ABSTRACT FROM AUTHOR]

Axial‐to‐central chirality transfer is an important strategy to construct chiral centers, where the axially chiral reagents are mostly limited to atropomerically stable ones. Reported herein is a RhIII‐catalyzed enantioselective spiroannulative synthesis of nitrones. The coupling proceeds via C−H arylation to give an atropomerically metastable biaryl, followed by intramolecular dearomative trapping under oxidative conditions with high degree of chirality transfer. [ABSTRACT FROM AUTHOR]

Efficient synthesis of 2-naphthols was realized by Ru(ii)-catalyzed C–H activation of aryl nitrones and intermolecular [3+3] annulation with α-diazo sulfonyl ketones under redox-neutral conditions. Easily available α-diazo sulfonyl ketones act as a three-carbon component in the reaction. [ABSTRACT FROM AUTHOR]

A rhodium(III)-catalyzed C−H amination of benzamides and isoquinolones with anthranils has been realized under assistance of weakly coordinating amide, leading to a bifunctionalized amination product which can further cyclize to acridine under in situ or ex situ conditions. [ABSTRACT FROM AUTHOR]

Rhodium(iii)-catalyzed mild benzylic α-fluoroalkenylation of 8-methylquinolines with gem-difluorostyrenes has been developed. This reaction occurred via C–H activation and C–F cleavage and is applicable to a wide range of substrates, leading to the synthesis of Z-alkenyl fluorides under mild and redox-neutral conditions with high regio- and stereoselectivity. [ABSTRACT FROM AUTHOR]

Ca2+/calmodulin-dependent protein kinase II δ (CaMKIIδ) has been shown to play a vital role in pathological events in myocardial ischemia/reperfusion (IR) injury. Dysregulation of autophagy in cardiomyocytes is implicated in myocardial IR injury. Here, we examined whether CaMKIIδ inhibition could protect against myocardial IR injury through alleviating autophagy dysfunction and evaluated the potential role of CaMKIIδ in Beclin-1-dependent autophagy in ischemia/reperfused hearts. This study was performed using isolated perfused rat hearts and H9c2 cardiac myoblasts. KN-93, but not KN-92, inhibited the phosphorylation of CaMKIIδ at Thr286 and its substrate phospholamban at Thr17 besides the CaMKIIδ activity in myocardial IR. KN-93, but not KN-92 significantly improved post-ischemic cardiac function and reduced cell death. In cultured H9c2 cardiac myoblasts, KN-93 or CaMKIIδ siRNA, but not KN-92, attenuated simulated IR (SIR)-induced cell death. Moreover, CaMKIIδ inhibition could alleviate IR-induced autophagic dysfunction as evidenced in reduced levels of Atg5, p62, and LC3BII in isolated rat hearts and H9c2 cardiac myoblasts. Furthermore, co-treatment with bafilomycin A1, a lysosomal inhibitor, in CaMKII inhibition-treated cells suggested that CaMKII inhibition alleviated autophagic flux. CaMKIIδ inhibition mitigated the phosphorylation of Beclin-1 at Ser90. As expected, Beclin-1 siRNA significantly decreased the levels of Beclin-1 and Beclin-1 phosphorylation accompanied by partial reductions in Atg5, LC3BII, p62, cleaved caspase-3 and cytochrome c. However, Beclin-1 siRNA had little effect on CaMKIIδ phosphorylation. Taken together, these results demonstrated that CaMKIIδ inhibition reduced myocardial IR injury by improving autophagy dysfunction, and that CaMKIIδ-induced autophagy dysfunction partially depended on the phosphorylation of Beclin-1. [ABSTRACT FROM AUTHOR]

Two kinds of indium-based MOF materials (In-MOF 1 and In-MOF 2) were synthesized using a solvothermal method using two different pyridine carboxylic acid ligands. Single crystal X-ray diffraction shows that In-MOF 1 is a three-dimensional frame containing four connected [In(CO2)4] units and nine connected [In3(μ3-O)(CO2)6N3] units, while In-MOF 2 is a three-dimensional structure with eight connected [In(CO2)3(CO)N] units. Moreover, the adsorption and separation properties of the MOFs for C2H2, CO2 and CH4 were investigated systematically in order to study the regulation of porosity by the subtle changes in the structure of organic linkers. The results show that both kinds of MOFs have certain gas adsorption and separation capacity, which is mainly determined by the structure, function and adjustable porosity. This work not only reports two MOFs with the potential to separate C2H2/CH4, CO2/CH4 and C2H2/CO2, but also provides valuable guidance for the design and synthesis of porous MOFs with better performance in the future. [ABSTRACT FROM AUTHOR]

Background: For high-risk stageIImismatch repair deficient (dMMR) colon cancers, the benefit of adjuvant chemotherapy remains debatable. The principal aim of this study was to evaluate the prognostic value of high-risk factors and the effect of oxaliplatin-based adjuvant chemotherapy among dMMR stageIIcolon cancers. Methods: Patients with stage II dMMR colon cancers diagnosed between June 2011 and May 2018 were enrolled in the study. Clinicopathological characteristics, treatment, and follow-up data were retrospectively collected. The high-risk group was defined as having one of the following factors: pT4 disease, fewer than twelve lymph nodes harvested (< 12 LNs), poorly differentiated histology, perineural invasion (PNI), lymphatic vascular invasion (LVI), or elevated preoperative carcinoembryonic antigen (CEA). The low-risk group did not have any risk factors above. Factors associated with disease-free survival (DFS) were included in univariate and multivariate Cox analyses. Results: We collected a total of 262 consecutive patients with stage II dMMR colon cancer. 179 patients (68.3%) have at least one high-risk factor. With a median follow-up of 50.1 months, the low-risk group was associated with a tended to have a better 3-year DFS than the high-risk group (96.4% vs 89.4%; P = 0.056). Both elevated preoperative CEA (HR 2.93; 95% CI 1.26–6.82; P = 0.013) and pT4 disease (HR 2.58; 95% CI 1.06–6.25; P = 0.037) were independent risk factors of recurrence. Then, the 3-year DFS was 92.6% for the surgery alone group and 88.1% for the adjuvant chemotherapy group (HR 1.64; 95% CI 0.67–4.02; P = 0.280). Furthermore, no survival benefit from oxaliplatin-based adjuvant chemotherapy was observed in the high-risk group and in the subgroups with pT4 disease or < 12 LNs. Conclusions: These data suggests that not all high-risk factors have a similar impact on stage II dMMR colon cancers. Elevated preoperative CEA and pT4 tumor stage are associated with increased recurrence risk. However, oxaliplatin-based adjuvant chemotherapy shows no survival benefits in stage II dMMR colon cancers, either with or without high-risk factors. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common malignancies, and early detection plays a crucial role in enhancing curative outcomes. While colonoscopy is considered the gold standard for CRC diagnosis, noninvasive screening methods of DNA methylation biomarkers can improve the early detection of CRC and precancerous lesions. Methods: Bioinformatics and machine learning methods were used to evaluate CRC‐related genes within the TCGA database. By identifying the overlapped genes, potential biomarkers were selected for further validation. Methylation‐specific PCR (MSP) was utilized to identify the associated genes as biomarkers. Subsequently, a real‐time PCR assay for detecting the presence of neoplasia or cancer of the colon or rectum was established. This screening approach involved the recruitment of 978 participants from five cohorts. Results: The genes with the highest specificity and sensitivity were Septin9, AXL4, and SDC2. A total of 940 participants were involved in the establishment of the final PCR system and the subsequent performance evaluation test. A multiplex TaqMan real‐time PCR system has been illustrated to greatly enhance the ability to detect precancerous lesions and achieved an accuracy of 87.8% (95% CI 82.9–91.5), a sensitivity of 82.7% (95% CI 71.8–90.1), and a specificity of 90.1% (95% CI 84.3–93.9). Moreover, the detection rate of precancerous lesions of this assay reached 55.0% (95% CI 38.7–70.4). Conclusion: The combined detection of the methylation status of SEPT9, SDC2, and ALX4 in plasma holds the potential to further enhance the sensitivity of CRC detection. [ABSTRACT FROM AUTHOR]

Regio‐ and stereoselective benzylic allylation of 8‐methylquinolines with (per)fluoroalkyl olefins has been realized via benzylic C−H activation and subsequent C−F cleavage. Both cobalt(III) and rhodium(III) catalysts can effect this transformation in good to high efficiency. The Rh(III)‐catalyzed system proceeded under moderate conditions with decent substrates scope, providing (Z)‐alkenyl fluorides with good to excellent regio‐ and stereoselectivity. [ABSTRACT FROM AUTHOR]

An abstract of the article "Cobalt(III)-Catalyzed C--C Coupling of Arenes with 7-Oxabenzonorbornadiene and 2-Vinyloxirane via C--H Activation" by Kong L, Yu S, and Tang G is presented.

An abstract of the article "Cobalt(III)-Catalyzed C-C Coupling of Arenes with 7-Oxabenzonorbornadiene and 2-Vinyloxirane via C-H Activation" by Lingheng Kong and colleagues are presented.

The article presents the cobalt(III)-catalyzed C–H activation of simple benzoate esters along with redox-neutral annulative coupling with internal alkynes which has resulted in the effective synthesis of indenones.

An abstract of the article "Redox-Neutral Couplings Between Amides and Alkynes via Cobalt(III)-Catalyzed C-H Activation" that was published in the previous issue is presented.

A negatively charged copolymer poly (MPC-co-AMPS) of 2-methacryloyloxyethyl phosphorylcholine (MPC) and 2-acrylamide-2-methyl propane sulfonic acid (AMPS) was designed and synthesized. Chitosan nanoparticles with cell outer membrane mimetic structure were prepared by electrostatic interaction between the sulfonic acid groups of poly (MPC-co-AMPS) and the protonated amino groups of chitosan. Effects of factors on influencing the particle size, distribution, and stability were investigated. The experimental results showed that cell membrane mimetic chitosan nanoparticles with controllable and homogeneous size ranged from 100 to 300 nm were prepared at the concentration of 0.1–2.0 mg/mL and the charge ratio of 0.5–1.1. Chitosan nanoparticles prepared can exist stably for more than 45 days when placed at 4° C and pH < 7.5. The cytotoxicity of the chitosan nanoparticles reduced significantly after surface modification with cell membrane mimetic structure, meeting the basic requirements of biomedical materials. The results suggest cell membrane mimetic chitosan nanoparticles prepared with polyanion and polycation obtain good biological compatibility and immune stealth ability, which has important academic significance and great application prospects. [ABSTRACT FROM AUTHOR]

The design of multifunctional hydrogel dressings to effectively promote wound healing is highly desirable in clinical trauma and surgery. Inspired by excellent mechanical properties of polyvinyl alcohol (PVA) and strong adhesion of polyphenols, gallic acid was grafted onto chitosan molecular chain (CS-GA) by free radical polymerization in this study, and PVA/CS-GA hydrogels were successfully prepared by repeated freeze-thaw method, without introducing toxic crosslinking agents. The prepared PVA/CS-GA hydrogels could adhere to various substrates, which confirmed excellent universal adhesion properties. The red blood cells adhesion ratio was 67.1%, indicating its potential for promoting wound coagulation. Meanwhile, the mechanical strength of PVA/CS-GA hydrogel was significantly enhanced, exhibiting approximately twice tensile strength and failure stretch compared with PVA hydrogel. Furthermore, attributing to GA molecule, PVA/CS-GA hydrogels not only showed favorable antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), but also could scavenge free radicals, showing effective antioxidant activity. The hydrogels also had good biocompatibility, met the basic requirements of biomedical materials and may promote wound repair. It should be noted that the content of GA had significant impact on cytotoxicity. Therefore, multifunctional PVA/CS-GA hydrogels with excellent mechanical, adhesion, antioxidant, antibacterial and biocompatible properties show promising potential applications in the biomedicine field, especially as functional wound dressings. Inspired by excellent mechanical properties of PVA and strong adhesion of polyphenols, PVA/CS-GA hydrogels with antibacterial, antioxidant, hemostatic, good biocompatibility, suitable adhesion and strong mechanical properties were successfully prepared by freeze-thaw method, which have great potential and application prospect as functional wound dressings. [Display omitted] • Multifunctional composite hydrogels are designed by non-toxic freeze-thaw method. • Polyphenol endows hydrogels with universal adhesion, and polyvinyl alcohol endows hydrogels with good elasticity. • The hydrogels exhibit excellent antioxidant, antibacterial and biocompatible properties. • The hydrogels can meet the requirements of ideal wound dressings. [ABSTRACT FROM AUTHOR]

Chiral RhIII catalysts can catalyze the asymmetric [4+1] spiroannulation of O-pivaloyl oximes with α-diazo homophthalimides under redox-neutral and acid/base-neutral conditions, leading to formation of chiral spirocyclic imines as a result of C–H activation and N–O cleavage. The reaction proceeded with high efficiency and features broad substrate scope, mild reaction conditions, and high to excellent enantioselectivities. [ABSTRACT FROM AUTHOR]

Reported herein is the rhodium(III)‐catalyzed C−H activation of anilines bearing an N‐isoquinolyl directing group for oxidative [3+2] annulation with four classes of internal alkynes, leading to atroposelective indole synthesis via dynamic kinetic annulation with C‐N reductive elimination constituting the stereo‐determining step. This reaction proceeds under mild conditions with high regio‐ and enantioselectivity and functional group compatibility. [ABSTRACT FROM AUTHOR]

Reported herein is the rhodium(III)‐catalyzed C−H activation of anilines bearing an N‐isoquinolyl directing group for oxidative [3+2] annulation with four classes of internal alkynes, leading to atroposelective indole synthesis via dynamic kinetic annulation with C‐N reductive elimination constituting the stereo‐determining step. This reaction proceeds under mild conditions with high regio‐ and enantioselectivity and functional group compatibility. [ABSTRACT FROM AUTHOR]

Nav1.5, encoded by SCN5A, has been associated with metastasis in colorectal cancer (CRC). Here, we investigated the mechanism by which Nav1.5 regulates tumor progression and whether Nav1.5 influences chemosensitivity to 5-fluorouracil (5-FU) in CRCs. CRC cases were evaluated for Nav1.5 expression. Elevated Nav1.5 expression was associated with poor prognosis in CRCs, whereas stage II/III patients with upregulated SCN5A expression could have better survival after receiving 5-FU-based adjuvant chemotherapy. In CRC cells, SCN5A knockdown reduced the proliferation, migration and invasion. According to RNA sequencing, SCN5A knockdown inhibited both the cell cycle and epithelial-mesenchymal transition. In addition, Nav1.5 stabilized the KRas-calmodulin complex to modulate Ras signaling, promoting Ca2+ influx through the Na+-Ca2+ exchanger and Ca2+ release-activated calcium channel. Meanwhile, SCN5A knockdown increased the 50% inhibitory concentration to 5-FU by upregulating 5-FU-stimulated apoptosis in CRCs. In conclusion, Nav1.5 could progress to proliferation and metastasis through Ca2+/calmodulin-dependent Ras signaling in CRC, and it could also enhance 5-FU-stimulated apoptosis. Clinically, patients with stage II/III CRCs with elevated SCN5A expression demonstrated poor prognosis, yet those patients could benefit more from 5-FU-based chemotherapy than patients with lower SCN5A expression. [ABSTRACT FROM AUTHOR]

Background: It was reported that tumor-expressed dickkopf-related (DKK) proteins affect micro-environment. However, the influence of DKK1 on colorectal cancer (CRC) liver oligometastases (CRCLOM) remains unclear.Methods: CRC cases after resection of liver oligometastases were enrolled in Sun Yat-Sen University Cancer Center with intact clinical data. Serum DKK1 was detected by ELISA assay. Immunofluorescent staining examination for CD3 and CD8 in slices were also conducted.Results: Among 65 patients included, the recurrence-free survival (RFS) and overall survival (OS) were significantly better in the low serum DKK1 group (RFS: P = 0.021; OS: P = 0.043). DKK1 was overexpressed in stage IV CRC patients in TCGA data. The number of CD8+ tumor-infiltrating lymphocytes (TILs) in invasive margin of CRC liver oligometastases was significantly higher in low serum DKK1 group (P = 0.042).Conclusion: Elevated serum DKK1 level was associated with poorer RFS and OS, and less CD8+ TILs in invasive margin in CRC liver oligometastases. DKK1 might serve as a supplementalprognostic factor for clinical risk score and a potential target for immunotherapy. [ABSTRACT FROM AUTHOR]

Cp*RhIII/IrIII complexes are known to play important roles in both C@H activation and transfer hydrogenation (TH). However, these two areas evolved separately. They have been integrated in redox- and chemodivergent coupling reactions of N-pyridylanilines with enones. The iridiumcatalyzed coupling with enones leads to the efficient synthesis of tetrahydroquinolines through TH from iPrOH. Counterintuitively, iPrOH does not serve as the sole hydride source, and the major reaction pathway involves disproportionation of a dihydroquinoline intermediate, followed by the convergent and iterative reduction of quinolinium species. [ABSTRACT FROM AUTHOR]

Abstract: Cp*RhIII/IrIII complexes are known to play important roles in both C−H activation and transfer hydrogenation (TH). However, these two areas evolved separately. They have been integrated in redox‐ and chemodivergent coupling reactions of N‐pyridylanilines with enones. The iridium‐catalyzed coupling with enones leads to the efficient synthesis of tetrahydroquinolines through TH from iPrOH. Counterintuitively, iPrOH does not serve as the sole hydride source, and the major reaction pathway involves disproportionation of a dihydroquinoline intermediate, followed by the convergent and iterative reduction of quinolinium species. [ABSTRACT FROM AUTHOR]

An efficient synthesis of 2-substituted quinolines from readily available cyclopropanols and imidamides has been developed, where the cyclopropanol acts as a C3 synthon. With the assistance of a bifunctional imidamide directing group, the reaction occurred via sequential C-H/C-C cleavage and C-C/C-N bond formation. [ABSTRACT FROM AUTHOR]

Metformin (Met) can improve atherosclerosis (As). Abnormal endothelin receptors [including endothelin type A (ET A) or type B (ET B) receptor] in vascular smooth muscle cells (VSMCs) are involved in As. Hyperhomocysteinemia (HHcy) is an independent risk factor for As. The present study was designed to test our hypothesis that Met inhibits the upregulation of endothelin receptors induced by homocysteine (Hcy) in VSMCs. Rat superior mesenteric artery (SMA) without endothelium, as an in vitro model, was cultured in serum-free medium for 24 h in the presence of Hcy with or without Met or nicotinamide (Nic). In vivo, rats received subcutaneous injections of Hcy in the presence or absence of Met or Nic for 3 weeks. Levels of protein expression were determined by Western blotting. The contractile responses to sarafotoxin 6c (an ET B receptor agonist) or ET-1 (an ET A / ET B receptor agonist) were studied using a sensitive myograph. The blood pressure of rats was measured using a noninvasive tail-cuff plethysmography method. The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ET A and ET B receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA. However, Nic (a Sirt1 inhibitor) recovered the levels of Met-inhibited endothelin receptors and acetylated p65. Furthermore, the in vivo results showed that Met not only significantly the inhibited HHcy-induced upregulation of endothelin receptors and acetylated p65 but also recovered the HHcy-induced decrease in Sirt1 in a dosage-dependent manner in SMA. In addition, Met significantly inhibited the HHcy-induced blood pressure elevation. However, these effects were reverted by Nic. In conclusion, these data demonstrated that Met inhibited the Hcy-induced increase in endothelin receptor expression by activating Sirt1 and then inhibiting NF-κB in VSMCs. These findings may provide insights into the mechanism underlying of Met-treated cardiovascular diseases induced by Hcy. Unlabelled Image [ABSTRACT FROM AUTHOR]

The front cover picture, provided by Xingwei Li and co ‐ workers, illustrates an efficient synthesis of 2 ‐ substituted quinolines from readily available cyclopropanols and imidamides, which has been developed with the cyclopropanol acting as a C3 synthon. With the assistance of a bifunctional imidamide directing group, the reaction occurred via sequential C−H/C−C cleavage and C−C/C−N bond formation. Details can be found in the communication on pages 1620 – 1625 (X. Zhou, Z. Qi, S. Yu, L. Kong, Y. Li, W. ‐ F. Tian, X. Li, Adv. Synth. Catal. 2017, 359, 1620 – 1625; DOI: 10.1002/adsc.201601278). [ABSTRACT FROM AUTHOR]

Bifunctional substrates (II) undergo a redox-neutral amination-cyclization reaction with 2-pyridones, indoles, and pyrroles to form quinoline-fused heterocycles. [ABSTRACT FROM AUTHOR]

Objective: To explore uterine arterial impedance and endometrial-subendometrial vascularity determined by two-dimensional Doppler ultrasonography (2D-DU) and three-dimensional ultrasonography and power Doppler angiography (3D-PDA) between patients with antiphospholipid antibodies–associated recurrent miscarriage (aPL-RM) and normal fertile women, and to further investigate the relationship between these parameters and endometrial microvessel density (MVD). Design: Prospective observational study. Setting: Tertiary-care fertility center. Patient(s): A total of 109 aPL-RM patients (aPL-RM group) and 49 normal fertile women (control group). Intervention(s): Uterine measurement by transvaginal ultrasonography and endometrial MVD in the midluteal phase was assessed for both groups. Main Outcome Measure(s): Endometrial thickness, volume, and MVD, uterine arterial pulsatility index (PI) and resistance index (RI), and the vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of endometrial and subendometrial regions were measured on day 7 of a natural cycle after ovulation. Result(s): Both groups had similar endometrial thickness, volume, and MVD and uterine arterial PI and RI. Endometrial VI, FI, VFI, and subendometrial FI were significantly reduced in the aPL-RM group compared with the control group. None of the uterine arterial 2D-DU and endometrial-subendometrial 3D-PDA parameters correlated with the endometrial MVD in both groups. Conclusion(s): Endometrial and subendometrial vascularity was significantly impaired in aPL-RM patients during natural midluteal phase compared with normal fertile women, and endometrial MVD did not correlate with any of the acquired vascularity parameters. [ABSTRACT FROM AUTHOR]