Short-term reproductive outcomes analysis and prediction of the modified uterine stent treatment for mild to moderate intrauterine adhesions: experience at a single institution.

BACKGROUND: To evaluate the efficacy of modified uterine stent in the treatment of mild-to-moderate intrauterine adhesions and explore the relative indicators affecting prognosis prediction. METHODS: A total of 115 patients with mild-to-moderate intrauterine adhesions received a modified uterine stent placement after hysteroscopy adhesiolysis. The second-look hysteroscopy operated after 3 months surgery, and the third-look hysteroscopy operated after 6 months surgery if necessary. The stent was removed when the cavity shape was repaired, then the reproductive outcomes were followed up one year. RESULTS: Menstrual blood volume, endometrial thickness and volume had increased significantly after 3 months surgery. The rates of cavity repaired were 86.96% (100/115) after 3 months surgery and 100% (115/115) after 6 months surgery cumulatively. Endometrial thickness after 3-months surgery was positively associated with uterine cavity shape repaired (P<0.01). The receive operating characteristic (ROC) curve showed the rate of uterine cavity shape repaired predicted by the model was 0.92, based on the endometrial thickness after 3-months surgery. The rate of pregnancy was 86.09% (99/115) in one year, while the rate of miscarriage accounted for 26.26% (26/99). The median time interval between stent removal and subsequent conception was 3 months. It showed adhesion recurrence was the risk factor for subsequent pregnancy (P<0.01). CONCLUSIONS: A modified uterine stent placement under hysteroscopy was an effective approach for mild-to-moderate intrauterine adhesions, which is easy to operate and worthy for clinical promotion. Endometrial thickness measured by ultrasonography probably has predictive value in adhesion recurrence and subsequent pregnancy. TRIAL REGISTRATION: ChiCTR2100051524. Date of registration (retrospectively registered): 26/09/2021.

183W Nuclear Magnetic Resonance and Photocatalysis Studies of Two Ruthenium-Decorated Isopolyoxometalates {Ru2W10} and {Ru2W13} via pH-Induced Assemblies.

Two structurally intriguing Ru-containing isopolyoxometalates [(Ru(OH))2O(W5O18)2]8- (1) and [(W5O18)(Ru2W8O31)]12- (2) were constructed from subtly different conditions. Single-crystal X-ray diffraction indicated that the precise pH modification has allowed us to trap a diruthenium-oxo core within different isopolyoxotungstate species. Compound 1 is the first sandwich-type ruthenium isopolyoxotungstate consisting of a linear {(HO)Ru-O-Ru(OH)} unit and two Lindqvist-type {W5} building blocks, while a ligand replacement of {W5} with an unusual {W8} ring in the case of compound 1 produced a unique embedded-type compound 2 with a quasi-linear {Ru-O-Ru} core. In addition to being determined in the solid state, crystal structures of 1 and 2 were also confirmed by 183W nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization-mass spectrometry (ESI-MS) in solution. 183W NMR spectrum demonstrated that the two-line pattern of 1 (with approximately 4:1 relative intensities) is consistent with the pseudo-D2h symmetry observed in the solid state. However, two other lines were observed in 2 according to the C2v symmetry but not in accord with the expected 4/4/4/1 ratio in the crystalline state, which indicated that the structure of 2 could not be maintained completely in aqueous solution. After recrystallizing the solid sample of 2 in water, the crystal structure of 2 partly converted to the structure of 1, and the transformation was determined by the combined results of 183W NMR, ESI-MS and single-crystal X-ray diffraction measurements. Catalytic investigations showed that their sodium salts presented excellent photocatalytic activities toward the benzylamine oxidation reaction induced by visible light (λ > 400 nm). The structures of the two compounds can still be maintained without a significant yield decrease after five continuous reaction cycles. Furthermore, both catalysts 1 and 2 could proceed with the oxidative coupling reaction smoothly for most of the primary benzylamine derivatives bearing various functional groups (H, F, Cl, Br, and Me) in good to excellent yields.

A Copper-Containing Polyoxometalate-Based Metal-Organic Framework as an Efficient Catalyst for Selective Catalytic Oxidation of Alkylbenzenes.

A copper-containing polyoxometalate-based metal-organic framework (POMOF), CuI12Cl2(trz)8[HPW12O40] (HENU-7, HENU = Henan University; trz = 1,2,4-triazole), has been successfully synthesized and well-characterized. In addition, the excellent catalytic ability of HENU-7 has been proved by the selective oxidation of diphenylmethane. Under the optimal conditions, the diphenylmethane conversion obtained over HENU-7 is 96%, while the selectivity to benzophenone is 99%, which outperforms most noble-metal-free POM-based catalysts. Moreover, HENU-7 is stable to reuse for five runs without an obvious loss in activity and also can catalyze the oxidation of different benzylic C-H with satisfactory conversions and selectivities, which implied the significant catalytic activity and recyclability.

Mechanism of the AppABLUF Photocycle Probed by Site-Specific Incorporation of Fluorotyrosine Residues: Effect of the Y21 pKa on the Forward and Reverse Ground-State Reactions.

The transcriptional antirepressor AppA is a blue light using flavin (BLUF) photoreceptor that releases the transcriptional repressor PpsR upon photoexcitation. Light activation of AppA involves changes in a hydrogen-bonding network that surrounds the flavin chromophore on the nanosecond time scale, while the dark state of AppA is then recovered in a light-independent reaction with a dramatically longer half-life of 15 min. Residue Y21, a component of the hydrogen-bonding network, is known to be essential for photoactivity. Here, we directly explore the effect of the Y21 pKa on dark state recovery by replacing Y21 with fluorotyrosine analogues that increase the acidity of Y21 by 3.5 pH units. Ultrafast transient infrared measurements confirm that the structure of AppA is unperturbed by fluorotyrosine substitution, and that there is a small (3-fold) change in the photokinetics of the forward reaction over the fluorotyrosine series. However, reduction of 3.5 pH units in the pKa of Y21 increases the rate of dark state recovery by 4000-fold with a Brønsted coefficient of ∼ 1, indicating that the Y21 proton is completely transferred in the transition state leading from light to dark adapted AppA. A large solvent isotope effect of ∼ 6-8 is also observed on the rate of dark state recovery. These data establish that the acidity of Y21 is a crucial factor for stabilizing the light activated form of the protein, and have been used to propose a model for dark state recovery that will ultimately prove useful for tuning the properties of BLUF photosensors for optogenetic applications.

High resolution spatiotemporal modeling of long term anthropogenic nutrient discharge in China.

High-resolution integration of large-scale and long-term anthropogenic nutrient discharge data is crucial for understanding the spatiotemporal evolution of pollution and identifying intervention points for pollution mitigation. Here, we establish the MEANS-ST1.0 dataset, which has a high spatiotemporal resolution and encompasses anthropogenic nutrient discharge data collected in China from 1980 to 2020. The dataset includes five components, namely, urban residential, rural residential, industrial, crop farming, and livestock farming, with a spatial resolution of 1 km and a temporal resolution of monthly. The data are available in three formats, namely, GeoTIFF, NetCDF and Excel, catering to GIS users, researchers and policymakers in various application scenarios, such as visualization and modelling. Additionally, rigorous quality control was performed on the dataset, and its reliability was confirmed through cross-scale validation and literature comparisons at the national and regional levels. These data offer valuable insights for further modelling the interactions between humans and the environment and the construction of a digital Earth.

Ultrafast infrared spectroscopy of an isotope-labeled photoactivatable flavoprotein.

The blue light using flavin (BLUF) domain photosensors, such as the transcriptional antirepressor AppA, utilize a noncovalently bound flavin as the chromophore for photoreception. Since the isoalloxazine ring of the chromophore is unable to undergo large-scale structural change upon light absorption, there is intense interest in understanding how the BLUF protein matrix senses and responds to flavin photoexcitation. Light absorption is proposed to result in alterations in the hydrogen-bonding network that surrounds the flavin chromophore on an ultrafast time scale, and the structural changes caused by photoexcitation are being probed by vibrational spectroscopy. Here we report ultrafast time-resolved infrared spectra of the AppA BLUF domain (AppA(BLUF)) reconstituted with isotopically labeled riboflavin (Rf) and flavin adenine dinucleotide (FAD), which permit the first unambiguous assignment of ground and excited state modes arising directly from the flavin carbonyl groups. Studies of model compounds and DFT calculations of the ground state vibrational spectra reveal the sensitivity of these modes to their environment, indicating that they can be used as probes of structural dynamics.

Photoexcitation of the blue light using FAD photoreceptor AppA results in ultrafast changes to the protein matrix.

Photoexcitation of the flavin chromophore in the BLUF photosensor AppA results in a conformational change that leads to photosensor activation. This conformational change is mediated by a hydrogen-bonding network that surrounds the flavin, and photoexcitation is known to result in changes in the network that include a strengthening of hydrogen bonding to the flavin C4═O carbonyl group. Q63 is a key residue in the hydrogen-bonding network, and replacement of this residue with a glutamate results in a photoinactive mutant. While the ultrafast time-resolved infrared (TRIR) spectrum of Q63E AppA(BLUF) is characterized by flavin carbonyl modes at 1680 and 1650 cm(-1), which are similar in frequency to the analogous modes from the light activated state of the wild-type protein, a band is also observed in the TRIR spectrum at 1724 cm(-1) that is unambiguously assigned to the Q63E carboxylic acid based on U-(13)C labeling of the protein. Light absorption instantaneously (<100 fs) bleaches the 1724 cm(-1) band leading to a transient absorption at 1707 cm(-1). Because Q63E is not part of the isoalloxazine electronic transition, the shift in frequency must arise from a sub picosecond perturbation to the flavin binding pocket. The light-induced change in the frequency of the Q63E side chain is assigned to an increase in hydrogen-bond strength of 3 kcal mol(-1) caused by electronic reorganization of the isoalloxazine ring in the excited state, providing direct evidence that the protein matrix of AppA responds instantaneously to changes in the electronic structure of the chromophore and supporting a model for photoactivation of the wild-type protein that involves initial tautomerization of the Q63 side chain.

Ultrafast transient mid IR to visible spectroscopy of fully reduced flavins.

The light sensing apparatus of many organisms includes a flavoprotein. In any spectroscopic analysis of the photocycle of flavoproteins a detailed knowledge of the spectroscopy and excited state dynamics of potential intermediates is required. Here we correlate transient vibrational and electronic spectra of the two fully reduced forms of flavin adenine dinucleotide (FAD): FADH(-) and FADH(2). Ground and excited state frequencies of the characteristic carbonyl modes are observed and assigned with the aid of DFT calculations. Excited state decay and ground state recovery dynamics of the two states are reported. Excited state decay occurs on the picosecond timescale, in agreement with the low fluorescence yield, and is markedly non single exponential in FADH(-). Further, an unusual 'inverse' isotope effect is observed in the decay time of FADH(-), suggesting the involvement in the radiationless relaxation coordinate of an NH or hydrogen bond mode that strengthens in the excited electronic state. Ground state recovery also occurs on the picosecond time scale, consistent with radiationless decay by internal conversion, but is slower than the excited state decay.

microRNA-222 promotes tumor growth and confers radioresistance in nasopharyngeal carcinoma by targeting PTEN.

MicroRNA-222 (miR­222) has been reported to be involved in the initiation, development and metastasis of tumors, as well as conferring resistance to chemotherapeutic drugs or radiotherapy in various types of cancer. However, the role and the underlying molecular mechanism of miR­222 specifically in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the biological function and underlying mechanism of in miR­222 was investigated in NPC tissue specimens and cell lines. miR­222 was upregulated in NPC tissues and malignant cell lines compared with adjacent normal samples and cell lines. miR­222 upregulation significantly increased NPC cell proliferation, colony formation and cell apoptosis. Furthermore, miR­222 upregulation conferred radioresistance. It was also confirmed that phosphatase and tensin homolog (PTEN) was a direct target for miR­222 in NPC cells. Alteration of miR­222 expression was demonstrated to regulate the phosphoinositide 3­kinase/protein kinase B pathway in NPC cells. These results suggest that miR­222 may act as an oncomir in NPC by targeting PTEN, and has potential as a therapeutic target in NPC.

TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis.

The differentiation of fibroblasts to myofibroblasts is critical for the development of idiopathic pulmonary fibrosis (IPF). T-cell lymphoma invasion and metastasis 1 (TIAM1) is known to be associated with amyotrophic lateral sclerosis 1 and colorectal cancer; however, its role in IPF is unclear. The aim of the present study was to investigate the expression and roles of TIAM1 in lung fibroblasts during pulmonary fibrosis. It was demonstrated that TIAM1 expression was significantly increased in fibrotic lung tissue and lung fibroblasts from bleomycin (BLM)-treated mice compared with control mice (P<0.05). TIAM1 expression and differentiation were significantly upregulated in human lung fibroblasts challenged with transforming growth factor-ß (TGF-ß) compared with unchallenged cells (P<0.05). Furthermore, inhibition of the nuclear factor (NF)-κB signaling pathway significantly attenuated TGF-ß-induced TIAM1 expression and decreased fibroblast differentiation in human lung fibroblasts (P<0.05). Similarly, overexpression of TIAM1 significantly inhibited TGF-ß-induced fibroblast differentiation, as indicated by decreased expression of fibronectin and α-smooth muscle actin (SMA; P<0.05). The results of the present study also demonstrated that TIAM1 knockdown increased TGF-ß-induced fibroblast differentiation (P<0.05). These findings suggest that TIAM1 expression is associated with lung fibroblast differentiation in pulmonary fibrosis via an NF-κB-dependent pathway, and that TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis.

Excited state structure and dynamics of the neutral and anionic flavin radical revealed by ultrafast transient mid-IR to visible spectroscopy.

Neutral and anionic flavin radicals are involved in numerous photochemical processes and play an essential part in forming the signaling state of various photoactive flavoproteins such as cryptochromes and BLUF domain proteins. A stable neutral radical flavin has been prepared for study in aqueous solution, and both neutral and anion radical states have been stabilized in the proteins flavodoxin and glucose oxidase. Ultrafast transient absorption measurements were performed in the visible and mid-infrared region in order to characterize the excited state dynamics and the excited and ground state vibrational spectra and to probe the effect of the protein matrix on them. These data are compared with the results of density functional theory calculations. Excited state decay dynamics were found to be a strong function of the protein matrix. The ultrafast electron transfer quenching mechanism of the excited flavin moiety in glucose oxidase is characterized by vibrational spectroscopy. Such data will be critical in the ongoing analysis of the photocycle of photoactive flavoproteins.

Vibrational assignment of the ultrafast infrared spectrum of the photoactivatable flavoprotein AppA.

The blue light using flavin (BLUF) domain proteins, such as the transcriptional antirepressor AppA, are a novel class of photosensors that bind flavin noncovalently in order to sense and respond to high-intensity blue (450 nm) light. Importantly, the noncovalently bound flavin chromophore is unable to undergo large-scale structural change upon light absorption, and thus there is significant interest in understanding how the BLUF protein matrix senses and responds to flavin photoexcitation. Light absorption is proposed to result in alterations in the hydrogen-bonding network that surrounds the flavin chromophore on an ultrafast time scale, and the structural changes caused by photoexcitation are being probed by vibrational spectroscopy. Here we report ultrafast time-resolved infrared spectra of the AppA BLUF domain (AppA(BLUF)) reconstituted with isotopes of FAD, specifically [U-(13)C(17)]-FAD, [xylene-(13)C(8)]-FAD, [U-(15)N(4)]-FAD, and [4-(18)O(1)]-FAD both in solution and bound to AppA(BLUF). This allows for unambiguous assignment of ground- and excited-state modes arising directly from the flavin. Studies of model compounds and DFT calculations of the ground-state vibrational spectra reveal the sensitivity of these modes to their environment, indicating they can be used as probes of structural dynamics.