Isolated Partial Anomalous Pulmonary Veins: A 10-Year Experience at a Single Center.

INTRODUCTION: Isolated partial anomalous pulmonary venous connection (PAPVC) is difficult to diagnose, and surgical indications remain controversial. We reviewed 10 y of isolated PAPVC cases. METHODS: The data of patients with isolated PAPVC admitted to the Anzhen Congenital Heart Disease Department from 2010 to 2019 were reviewed retrospectively. RESULTS: Thirty patients, aged between 4 mo and 32 y, were included in this study. Significant correlations were found between the right ventricle (RV), end-diastolic dimension Z-score (RVED-z) and age (r = 0.398, P = 0.03), and between estimated pulmonary pressure and age (r = 0.423, P = 0.02). However, no significant correlations were found between the RVED-z and the number of anomalous pulmonary veins (r = 0.347, P = 0.061), between estimated pulmonary pressure and the RVED-z (r = 0.218, P = 0.248), and between estimated pulmonary pressure and the number of anomalous veins (r = 0.225, P = 0.232). Transthoracic echocardiography (TTE) confirmed 90% of isolated PAPVC cases. Surgical repair was performed in 29 patients with RV enlargement, persistent low weight, pulmonary hypertension, or respiratory symptoms. Among the surgical patients, nine had elevated pulmonary pressure before surgery, which decreased postoperatively; no mortality or reintervention was observed. The mean duration of echocardiographic follow-up was 1.9 y. CONCLUSIONS: TTE is recommended for routine assessments, and further clarification can be obtained with computed tomography when TTE proves inconclusive for diagnosis. Transesophageal echocardiography and computed tomography are further recommended for adult patients if TTE fails to provide clear results. PAPVC should be considered as an underlying cause when unexplained RV enlargement is observed. Surgery is recommended for patients with RV enlargement, pulmonary hypertension, or respiratory symptoms.

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells.

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs.

A Versatile Extended Stöber Approach to Monodisperse Sub-40 nm Carbon Nanospheres for Stabilizing Atomically Dispersed Fe─N4 Sites Toward Efficient Oxygen Reduction Electrocatalysis.

The development of atomically dispersed iron-nitrogen-carbon (Fe─N─C) catalysts as an alternative to precious platinum holds great potential for the substantial progress of a variety of oxygen reduction reaction (ORR)-associated energy conversion technologies. Nevertheless, the precise synthesis of Fe─N─C single atomic catalysts (SACs) with a high density of accessible active sites and pronounced electrocatalytic performance still remains an enormous challenge. Herein, an innovative extended Stöber method is designed for the controllable preparation of monodisperse small-sized N-doped carbon colloidal nanospheres (≈40 nm) anchoring atomically isolated Fe─N4 sites (abbreviated as Fe-SA@N-CNSs hereafter) with a narrow size distribution and high uniformity. Benefiting from the single Fe─N4 moieties and the unique spherical carbon substrate, the resultant Fe-SA@N-CNSs exhibit excellent ORR activity, outstanding long-term durability, and methanol tolerance in KOH electrolyte. More impressively, when further assembled into a flexible solid-state rechargeable zinc-air battery (ZAB), the Fe-SA@N-CNSs-driven ZAB delivers a higher open circuit voltage, a larger power density, and robust cycling/mechanical stability, outperforming the state-of-the-art Pt/C-based counterpart and further testifying the great potential of the as-prepared Fe-SA@N-CNSs in diverse ORR-related practical energy devices. The developed extended Stöber method provides an efficient and versatile avenue toward the preparation of a series of well-defined SACs for diverse electrocatalytic systems.

Au(I)-Catalyzed Regioselective Hydrofluorination of Propargylamines Using Aqueous HF.

Gold-catalyzed regioselective hydrofluorination of alkynes using aqueous HF has been achieved by employing an amide directing group. For both aryl- and alkyl-substituted propargylamines, the fluorination occurred at the site distal to the amino group.

A one-step base-free synthesis of N-arylamides via modified pivaloyl mixed anhydride mediated amide coupling.

Pivalic anhydride is shown to be an effective reagent for direct amidation of carboxylic acids with N-alkyl anilines. The only by-product of this reaction is nontoxic pivalic acid, which can be easily removed by aqueous workup. The reactions are conducted under mild conditions and found to be compatible with a range of carboxylic acids, including aromatic, heterocyclic, acrylic, and aliphatic carboxylic acids and amino acids generating the desired amides in short reaction times.

A multi-criteria analysis framework for water transfers to improve the water environments under strong artificial interventions in highly urbanized areas.

Water transfer is an effective measure to enhance hydrodynamic and water quality in highly urbanized areas. The effect of water transfer in highly urbanized areas is affected by strong artificial interventions, and it is difficult to evaluate the improvement of multiple indicators of many sections after water transfer. At present, there is no analysis framework directly evaluates the improvement of water environment under strong artificial interventions, making it difficult to determine the optimal scheduling of hydraulic projects. This study constructed a multi-criteria analysis framework for evaluating the improvement of water environment including index layers of water quality improvement, hydrodynamic improvement and economic cost, and designed corresponding element layers for each index layer. The weights of each element were determined based on fuzzy analytical hierarchy process, and the fuzzy comprehensive evaluation method was used for comprehensive evaluation. The framework was applied in Xishan District in highly urbanized Taihu Lake Basin, and the results showed that the proposed framework could effectively determine the optimal scheduling of hydraulic projects. Water quality compliance rate for the optimal water transfer scheme achieved in Xishan District was 82%, average rate of water quality improvement was 31%, and proportion of cross-sections meeting the Class III water quality standard was 61%. Average flow velocity was 0.10 m/s, proportion of the optimal velocity was 39%, and proportion of stagnant sections was 32%. Furthermore, the impact of regional control projects on the effect of water transfer was much greater than local projects, consequently, the best scheduling mode for regional control projects should be first determined, and then the scheduling combination for local projects. This study can provide a new framework for the assessment of water transfers to improve the water environments and a scientific basis for the dispatching of hydraulic projects in Taihu Lake Basin.

The protective effects of glutamine against bronchopulmonary dysplasia are associated with MKP-1/MAPK/cPLA2 signalingmediated NF-kappaB pathway.

Glutamine is proven to have potential therapeutic effects on decreasing hyperoxia-induced acute pulmonary injury. The aim of this study is to investigate the effects and mechanism of glutamine on bronchopulmonary dysplasia (BPD) induced by hyperoxia in rat alveolar type II epithelial cells (AECIIs) RLE-6TN. Following hyperoxia induction and glutamine treatment, ROS levels were detected by DCFH-DA assay and TUNEL staining was performed to detect cell apoptosis. The levels of inflammatory indicators and expression of apoptosis-related proteins were detected through ELISA and Western blot, respectively. Besides, the expression of related proteins in mitogen-activated protein kinase phosphatase-1 (MKP-1)/mitogen-activated protein kinases (MAPK)/cytoplasmic phospholipase A2 (cPLA2) signaling was also detected by Western blot. To further analyze the role of MKP-1/MAPK/cPLA2 signaling, MKP-1 was silenced and anisomycin was used to treat cells, respectively. It was shown that glutamine significantly decreased inflammation, oxidative stress and apoptosis in hyperoxia-induced cells while MKP-1 interference and anisomycin were able to reverse these effects, suggesting that the protective effects of glutamine on BPD induced by hypoxia were related to MKP-1/MAPK/cPLA2 signaling. To sum up, glutamine protected against BPD by decreasing inflammation, oxidative stress and apoptosis via MKP-1/MAPK/cPLA2 signaling.

Crystallization Selectivity of Ribavirin Solution and Amorphous Phase.

Crystallization selectivity is an important principle in polymorph control. Ribavirin Form I, Form II, DMSO solvate, and amorphous ribavirin are prepared, and the short-range order similarities between these solid forms and ribavirin aqueous solution and DMSO solution are compared via mid-frequency Raman difference spectra (MFRDS). The crystallization process from amorphous ribavirin to Form I and from solution to amorphous phase is explained. Reasons for the difficulty in preparing the DMSO solvate are proposed. The rationale provided for the crystallization selectivity provides a foundation for the synthesis of metastable phases with a robust and convenient method.

[Mechanism of Chaenomelis Fructus in treatment of rheumatoid arthritis based on network pharmacology and experimental verification].

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1ß(IL-1ß). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1ß, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

Photoredox-Catalyzed Tandem Radical Cyclization/Hydroxylation for the Synthesis of 4-Hydroxyalkyl-3,3-difluoro-γ-lactams.

The photoredox-catalyzed radical difluoroalkylation/cyclization/hydroxylation cascade reaction of various 2-bromo-2,2-difluoro-N-arylacetamides containing unactivated alkene moieties has been developed, providing green and efficient access to various 4-hydroxyalkyl-3,3-difluoro-γ-lactams. Control experiments confirmed a radical process, and inexpensive air acted as the sole hydroxy resource. In addition, the highlights of this protocol include good tolerance for a variety functional groups, lower photocatalyst loading, and ease of operation.

Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression.

Bile acid (BA) homeostasis is regulated by the extensive cross-talk between liver and intestine. Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders. In this study we investigated the regulatory mechanisms of BA in the intestine. We showed that the BA levels in the gallbladder and faeces were significantly increased, whereas serum BA levels decreased in systemic Krüppel-like factor 9 (Klf9) deficiency (Klf9-/-) mice. These phenotypes were also observed in the intestine-specific Klf9-deleted (Klf9vil-/-) mice. In contrast, BA levels in the gallbladder and faeces were reduced, whereas BA levels in the serum were increased in intestinal Klf9 transgenic (Klf9Rosa26+/+) mice. By using a combination of biochemical, molecular and functional assays, we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter (Asbt) in the terminal ileum to enhance BA absorption in the intestine. Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression. This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.

Neutrophil membrane engineered HucMSC sEVs alleviate cisplatin-induced AKI by enhancing cellular uptake and targeting.

Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.

Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

Emergency surgical treatment of total anomalous pulmonary venous connection.

BACKGROUND: This study explored the strategy and effect of emergency surgical treatment for total anomalous pulmonary venous connection (TAPVC). METHODS: From March 2009 to February 2020, 78 patients with TAPVC underwent emergency surgical correction. There were 51 males and 27 females. The median age was 39.5 days, and the median weight was 4.0 kg. Preoperative percutaneous oxygen saturation was 80.8% ± 4.5%. RESULTS: Of the cases investigated, seven died during the perioperative period; 16 had a delayed chest closure; 19 had early pulmonary vein obstruction; two had secondary tracheal intubation; one had a brain complication; and one had a third-degree atrioventricular block. Low weight, younger age, cardiopulmonary bypass time, and aortic cross-clamp time were identified as risk factors for early mortality. During the follow-up from 4 to 137 months, 12 cases did not respond to follow-up requests. Ten patients died within 1-6 months after discharge. One patient underwent reoperation due to pulmonary vein obstruction. The longer hospital stay after the operation and intensive care unit time were identified as risk factors for late mortality. CONCLUSIONS: Emergency surgery for severe TAPVC patients after admission achieved good short-term results. Prenatal diagnosis should be strengthened to save more patients. The higher late mortality rate of such patients indicates that post-discharge management should be strengthened to reduce the occurrence of post-discharge deaths.

Study on preparation, stability, thermal conductivity, and viscosity of silver nanoparticles-decorated three-dimensional graphene-like porous carbon hybrid nanofluids.

In the present study, a novel silver nanoparticles-decorated three-dimensional graphene-like porous carbon (Ag/3D GPC) nanocomposite has been synthesized via the method of carbonization and reduction of silver ions at the same time. This Ag/3D GPC nanocomposite possess an interconnected network of well crystalized and submicron-sized macropores with thin graphene walls of several nanometers, where silver nanoparticles distributing uniformly. The water based and ethylene glycol based Ag/3D GPC hybrid nanofluids have been prepared without any surfactant. The hybrid nanofluids with low concentration (<0.8 wt%) can be steadily dispersed for more than six months. The thermal conductivity enhancement for the nanofluids with 0.1 wt% can reach 10.3% and 8.8% at 25 °C compared with pure water and ethylene glycol, respectively. The viscosity of nanofluids is investigated, the temperature dependence of the dynamic viscosity obeys an Arrhenius-like behavior. The prepared Ag/3D GPC hybrid nanofluids with good stability and thermal conductivity are promisingly considered to be used in heat transfer field.

Novel phenylpyrimidine derivatives containing a hydrazone moiety protect rice seedlings from injury by metolachlor.

One strategy for solving the phytotoxicity of herbicides is to apply herbicide safeners that can efficiently alleviate the injuries of agricultural crops caused by herbicides. When metolachlor, a chloroacetamide herbicide, is applied with paddy rice, for example, the mechanisms associated with metolachlor and its residue negatively impact on the growth and yields of rice. To identify novel high-activity herbicide safener candidates for metolachlor, a series of (E)-4-(2-substituted hydrazinyl)-6-chloro-2-phenyl pyrimidines were synthesized and their structures were confirmed using IR (infrared radiation), 1H NMR, 13C NMR, and HRMS (high resolution mass spectrometry). The herbicide safener activities were then evaluated via primary tests. Compounds 3i and 3t were found to have the best herbicide activity on plant height. These compounds were then further screened for their activities at lower concentrations and showed better or similar activities compared to the positive control fenclorim, a commercial herbicide safener. The compounds 3i and 3t significantly enhanced glutathione S-transferase (GST) activity related with the herbicide safener activity in both shoots and roots tissues. Moreover, a qPCR (Real-time quantitative polymerase chain reaction) analysis found that the 3i and 3t treatments enhanced the expressions of OsGSTU3, OsGsTU39, and OsGSTF5. Finally, the results of an acute toxicity assessment with zebrafish (Danio rerio) embryos using treatments 3i and 3t indicated they are relatively safe to aquatic organisms.

[Dynamic characteristics of brain networks in patients with irritable bowel syndrome based on functional magnetic resonance imaging].

The disorder of brain-gut interaction is an important cause of irritable bowel syndrome (IBS), but the dynamic characteristics of the brain remain unclear. Since there are many shortcomings for evaluating brain dynamic nature in the previous studies, we proposed a new method based on slope calculation by point-by-point analysis of the data from functional magnetic resonance imaging, and detected the abnormalities of brain dynamic changes in IBS patients. The results showed that compared with healthy subjects, there were dynamic changes in the brain for the IBS patients. After correction by false discovery rate (FDR), significant abnormalities were only found in two functional connections of the right posterior cingulate gyrus linked to left middle frontal gyrus, and the right posterior cingulate gyrus linked to left pallidus. The above results of the brain dynamic analysis were totally different from those of the brain static analysis of IBS patients. Our findings provide novel complementary information for illustrating the central nervous mechanism of IBS and may offer a new direction to explore central target for patients with IBS.

A mitochondria-targeted fluorescent probe for hypochlorite sensing and its application in bioimaging.

A coumarin-diaminomaleonitrile derivative (C-DAN) was designed and prepared. Upon addition of hypochlorite (OCl-), the fluorescence emission peak of C-DAN at 475 nm was gradually enhanced with a rapid response (within 5 s); meanwhile, the color of the solution changed from dark red to bright yellow which can be observed with the naked eye. Furthermore, owing to its advantages including high selectivity, sensitivity, and low toxicity, our C-DAN probe has been applied for detecting OCl- in living cells and zebrafish, indicating it is an ideal tool for biological applications.

Enhanced Transformation of Emerging Contaminants by Permanganate in the Presence of Redox Mediators.

In this study, a permanganate/redox mediator system for enhanced transformation of a series of emerging contaminants was evaluated. The presence of various redox mediators (i.e., 1-hydroxybenzotriazole, N-hydroxyphthalimide, violuric acid, syringaldehyde, vanillin, 4-hydroxycoumarin, and p-coumaric acid) accelerated the degradation of bisphenol A (BPA) by Mn(VII). Since 1-hydroxybenzotriazole (HBT) exhibited the highest reactive ability, it was selected to further investigate the reaction mechanisms and quantify the effects of important reaction parameters on Mn(VII)/redox-mediator reactions with BPA and bisphenol AF (BPAF). Interestingly, not only HBT accelerated the degradation of BPA, but also BPA enhanced the decay of HBT. Evidence for the in situ formation of HBT· radicals as the active oxidant responsible for accelerated BPA and BPAF degradation was obtained by radical scavenging experiments and 31P NMR spin trapping techniques. The routes for HBT· radical formation involving Mn(VII) and the electron-transfer pathway from BPA/BPAF to HBT· radicals demonstrate that the Mn(VII)/HBT system was driven by the electron-transfer mechanism. Compared to Mn(VII) alone, the presence of HBT totally inhibited self-coupling of BPA and BPAF and promoted ß-scission, hydroxylation, ring opening, and decarboxylation reactions. Moreover, Mn(VII)/HBT is also effective in real waters with the order of river water > wastewater treatment plant (WWTP) effluent > deionized water.

A Cataluminescence Sensor Based on NiO Nanoparticles for Sensitive Detection of Acetaldehyde.

Sensitive and selective detection of harmful gas is an important task in environmental monitoring. In this work, a gas sensor based on cataluminescence (CTL) for detection of acetaldehyde was designed by using nano-NiO as the sensing material. The sensor shows sensitive response to acetaldehyde at a relatively low working temperature of 200 °C. The linear range of CTL intensity versus acetaldehyde concentration is 0.02-2.5 mg/L, with a limit of detection of 0.006 mg/L at a signal-to-noise ratio of three. Mechanism study shows that electronically excited CO2 is the excited intermediate for CTL emission during the catalytic oxidation of acetaldehyde on the NiO surface. The proposed sensor has promising application in monitoring acetaldehyde in residential buildings and in the workplace.