The effect and mechanism of low-molecular-weight heparin on the decidualization of stromal cells in early pregnancy.

OBJECTIVE: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes. METHODS: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group (n = 10 mice in each group). Halfway through the 12th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH. RESULTS: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice (p < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA (p < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased (p < 0.05). CONCLUSIONS: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

Recyclable Luminescence Sensor for Dinotefuran in Water by Stable Cadmium-Organic Framework.

Due to the widespread use of dinotefuran around the world, its impact on food and environmental safety has aroused great concern, and the establishment of a rapid and convenient approach for dinotefuran detection is necessary but challenging. Herein, we synthesized a unique three-dimensional framework {[(CH3)2NH2]2[Cd3(BCP)2]·10H2O·3.5DMF}n (1). Single-crystal X-ray analysis indicates that 1 possesses a 4,8-connected anion framework that corresponds to alb topology, with a one-dimensional rectangular channel along the c-axis with the size of 4 Å × 10 Å. Compound 1 displays satisfactory solvent and thermal stability. Luminescent investigations reveal that 1 can selectively detect dinotefuran by fluorescence quenching among other pesticides, displaying excellent anti-interference performance with common ions in water. Importantly, the limit of detection is as low as 2.09 ppm, which is far below the residual concentration of the U.S. food standard. A fluorescence quenching mechanism study shows that there exists competitive energy absorption and static quenching processes. To our knowledge, 1 is the first MOF-based fluorescence probe for dinotefuran detection.

An Ultrastable Matryoshka [Hf13 ] Nanocluster as a Luminescent Sensor for Concentrated Alkali and Acid.

Stable metal clusters that can resist both highly concentrated acid and alkali are unknown. Herein, we present a discrete neutral cluster, Hf13 (µ4 -O)8 (OCH3 )36 (1), which features extraordinary chemical stability by preserving its crystalline state in concentrated aqueous solutions of both acid (10 m HNO3 ) and alkali (20 m boiling NaOH). Importantly, 1 can serve as a luminescent probe for detecting both concentrated alkali (20 m NaOH) and strong acid (1 m HNO3 ) with high selectivity and repeatability. DFT studies of the electronic structure and bonding revealed that 1 has an extremely large HOMO-LUMO gap due to strong d π-p π bonding that accounts for the ultrahigh stability.

Two Stable Heterometal-MOFs as Highly Efficient and Recyclable Catalysts in the CO2 Coupling Reaction with Aziridines.

Two stable heterometal-organic frameworks, {Na[LnCo(DATP)2 (Ac)(H2 O)](NO3 )⋅DMA⋅11 H2 O}n (Ln=Er(1) and Yb(2)), have been prepared with H2 DATP (4'-(3,5-dicarboxyphenyl)-2,2':6',2'''-terpyridine) as organic building block. These two isostructural compounds featuring two-dimensional layer architectures possess outstanding thermal stabilities and excellent chemical stabilities in common organic solvents and different acid/base solutions with pH range changing from 1 to 13. Moreover, compounds 1 and 2 serving as heterogeneous catalysts can efficiently catalyse the CO2 fixation reaction with various aziridines to result in corresponding oxazolidinones at 70 °C. Importantly, a good recyclable performance of 1 for at least 10 cycles is observed based on the experimental results, which are further confirmed by PXRD, TGA and ICP analyses.

Solvent-dependent variations of both structure and catalytic performance in three manganese coordination polymers.

Three new manganese 4'-(3,5-dicarboxyphenyl)-2,2':6',2'''-terpyridine (H2DATP) metal-organic framework materials have been generated through regulating the ratios of a binary solvent mixture (DMA/H2O) under solvothermal conditions. Compound 1 {[Mn2(DATP)(HDATP)(H2O)4](OH)·10H2O}n displaying a one-dimensional (1D) chainlike structure was crystallized from the DMA/H2O mixture with a molar ratio of 1 : 1, while the two-dimensional (2D) layer species, {[Mn(DATP)(H2O)]·2H2O}n (2) was produced by increasing the ratio of DMA/H2O to 5 : 1. Interestingly, the crystallization in pure DMA yields a three-dimensional (3D) interpenetrating network {[Mn(DATP)]·4H2O}n (3), featuring higher solvent stability and pH stability than compounds 1 and 2. It is proved that solvent not only influences the structural transformation process of crystals but also has a significant effect on their properties. These three compounds present different catalytic performances in the CO2 cycloaddition to epoxides with various substituent groups into corresponding cyclic carbonates, and only 3 can serve as an efficient and recyclable catalyst at mild temperature.

A Sensitive Luminescent Acetylacetone Probe Based on Zn-MOF with Six-Fold Interpenetration.

A novel metal-organic framework {[Zn(XL)2 ](ClO4 )2 ⋅6 H2 O}n (XL=N,N'-bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxdiimide bi(1,2,4-triazole)) was synthesized and structurally characterized, presenting the first example of six-fold interpenetrating 3 D framework with the topology type of sqc6, which displays high thermostability and solvent stability. Additionally, the luminescence investigations reveal that this MOF can sensitively and selectively detect acetylacetone with a detection limit of 1.72 ppm. More importantly, it is rather rare for an MOF-based luminescence probe to serve as a sensor to effectively detect acetylacetone.

Bilaterally Primary Cementless Total Hip Arthroplasty for Severe Hip Ankylosis with Ankylosing Spondylitis.

OBJECTIVES: Total hip arthroplasty is a reliable therapeutic intervention in patients with ankylosing spondylitis, in whom the aims of surgery are to reduce pain, restore hip function and improve quality of life. The current study is a retrospective analysis of the clinical and radiographic findings in a consecutive series of patients with hip ankylosis associated with severe ankylosing spondylitis who underwent bilateral primary total hip arthroplasty using non-cemented components. METHODS: From June 2008 to May 2012, total hip arthroplasty was performed on 34 hips in 17 patients with bilateral ankylosis caused by ankylosing spondylitis. The study patients included 13 men and 4 women with a mean age of 24.2 years. The mean duration of disease was 8.3 years and the average duration of hip involvement was 7.6 years. All patients had severe hip pain and dysfunction with bilateral bony ankylosis and no range of motion preoperatively and all underwent bilateral cementless total hip arthroplasty performed by a single surgeon. Joint pain, range of motion (ROM), and Harris hip scores were assessed to evaluate the postoperative results. RESULTS: At a mean follow-up of 31.7 months, all patients had experienced significant clinical improvement in function, ROM, posture and ambulation. At the final follow-up, the mean postoperative flexion ROM was 134.4° compared with 0° preoperatively. Similar improvements were seen in hip abduction, adduction, internal rotation and external rotation. Postoperatively, 23 hips were completely pain-free, six had only occasional discomfort, three mild to moderate pain and two severe pain. The average Harris Hip Score improved from 23.7 preoperatively to 65.8 postoperatively. No stems had loosened at the final follow-up in any patient, nor had any revision surgery been required. CONCLUSIONS: Bilateral severe hip ankylosis in patients with ankylosing spondylitis can be treated with cementless bilateral synchronous total hip arthroplasty, which can greatly improve hip joint function and relieve pain without significant complications. Provided the overall physical condition of a patient and their economic situation make surgery a feasible option and the surgeon is experienced, this treatment is a worthwhile surgical intervention for bilateral hip bony ankylosis. However, the technically demanding nature of the procedure and potential pre- and post-operative problems should not be underestimated.

Lanthanide-based metal-organic frameworks as luminescent probes.

Lanthanide-based metal-organic frameworks (Ln-MOFs), as notable materials, are constructed by Ln3+ ions and organic ligands, or Ln3+ ions functionalizing non-Ln-MOFs, and exhibit promising applications in various fields. Over the past decades, quite a lot of investigations of Ln-MOFs have been carried out, and many good results have been obtained. Among these results, Ln-MOFs as luminescent probes for unique detection are gradually becoming a hot topic due to their fast and effective luminescent response for the targeted substance. In this perspective article, we discuss the construction of luminescent Ln-MOFs, their applications in possible detection mechanisms, and summarize some examples of Ln-MOFs as luminescent probes for sensing cations, anions and small molecules.

New insights into myeloid-derived suppressor cells and their roles in feto-maternal immune cross-talk.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells that suppress both innate and adaptive immune responses through multiple mechanisms. In recent years, much of our knowledge of the function of MDSCs has come from cancer studies. However, a few recent advances have begun to characterize MDSCs in feto-maternal immune cross-talk. The microenvironment at the fetal-maternal interface is a complex milieu of trophoblasts and maternally-derived cells, which are biased to tolerogenic and Th2-type responses. Current data reveal that MDSCs accumulate at the fetal-maternal interface in healthy pregnancies. Yet, little is known about how MDSCs develop and why the response of MDSCs is heavily granulocytic. In this review, we discuss recent findings on the molecular mechanisms that regulate the expansion and function of MDSCs, in addition to various roles of MDSCs implicated in the modulation of feto-maternal immune cross-talk. Understanding the roles of MDSCs in inducing maternal-fetal tolerance, which is compromised in patients suffering from pregnancy complications, including preeclampsia, intrauterine growth restriction, spontaneous abortion, and preterm birth, we thus propose that the immunomodulatory activity of MDSCs should be carefully considered for the therapeutic approaches targeting pregnancy complications.

Assembly of single molecular magnets from dinuclear to 2D Dy-compounds with significant change of relaxation energy barriers.

A dinuclear Dy(III) compound (1) was structurally and magnetically characterized, displaying a single-molecule magnet (SMM) behavior with a relaxation energy barrier of 21(1) K. Interestingly, by only adding a suitable substituent on the ligand in , as an SMM building unit, can be further assembled into a two-dimensional (2D) framework (2), which possesses a typical SMM behavior and a high relaxation energy barrier of 68(2) K. The result implied that the assembly of an SMM can effectively tune the energy barrier. To our knowledge, a cluster-based SMM assembled into a new 2D framework with SMM behavior is seldom reported.

Self-assembly of heterometallic Ln(III)-Co(II) coordination polymers: syntheses, structures, and magnetic studies.

A family of heterometallic 4f-3d coordination polymers with the common formula [LnCo1.5(L)2(H2O)5]n (Ln = Pr(1), Eu(2), Gd(3), Tb(4), Dy(5), Ho(6), and Er(7), and H3L = 4-(carboxymethoxy)isophthalic acid) was obtained under solvothermal conditions with the effect of NaN3, which was involved in the reactions but not in the final structure. All of the compounds were isostructural, and had a two-dimensional wave-like structure based on centrosymmetric [LnO2Co]-Co-[LnO2Co] motifs. The results of the magnetic measurements displayed that ferromagnetic interactions occurred in the frameworks (3-7) containing "heavy" lanthanide ions (Gd, Tb, Dy, Ho, and Er), which should be ascribed to the coupling between the Ln(III) and Co(II) ions. Furthermore, compound 5, containing Dy(III) ions, displayed field-induced slow magnetic relaxation.

First tetrazole-bridged d-f heterometallic MOFs with a large magnetic entropy change.

A novel 3D tetrazole-bridged 3d-4f heterometallic MOF {(H3O)3[Gd3Mn2(Trz)4]·12H2O}n (1) with a hexanuclear [Gd6] cluster was obtained via in situ [2+3] cycloaddition reaction and structurally characterized, possessing good solvent and thermal stabilities, as well as a large magnetic entropy change -ΔS(m) = 40.3 J kg(-1) K(-1) for ΔH = 7 T at 2.0 K. To our knowledge, it is the first example of tetrazole-bridged 3d-4f heterometallic MOFs.

SDF-1/CXCR4 promotes epithelial-mesenchymal transition and progression of colorectal cancer by activation of the Wnt/ß-catenin signaling pathway.

Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial-mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and ß-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with ß-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/ß-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/ß-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/ß-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression.

Expression and significance of the novel tumor-suppressor gene SMG-1 in hepatocellular carcinoma.

Recent studies have demonstrated that SMG-1, a newly characterized member of the family of phosphatidylinositol 3-kinase-related protein kinases (PIKKs), is involved in tumorigenesis as a new tumor suppressor. However, its expression and significance in hepatocellular carcinoma (HCC) remain obscure. The present study investigated SMG-1 expression in HCC tissue specimens, aimed at defining the association with clinicopathological significance. Both immunohistochemistry and qRT-PCR were employed to analyze SMG-1 expression in 157 HCC and corresponding distant normal tissue specimens. The results revealed that expression of SMG-1 was significantly lower in the HCC tissue specimens than that in the distant normal tissues. Moreover, a lower expression level of SMG-1 was significantly correlated with serum α-fetoprotein level (P=0.001), poorly differentiated tumors (P=0.009) and more advanced TNM stage (P<0.001). Further study showed that SMG-1 expression was exactly associated with tumor differentiation and clinical stage in HCC. Kaplan-Meier analysis indicated that low SMG-1 expression was related to poor overall survival, and the prognostic impact of SMG-1 was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low SMG-1 expression was an independent prognostic marker for an unfavorable overall survival. We conclude that SMG-1 is downregulated in HCC and may represent a promising biomarker for predicting the prognosis of HCC, including the prognosis of early-stage patients.