[Clinical characteristics of pregnancy complicated with inflammatory bowel disease].

OBJECTIVE: To analyze the clinical characteristics of patients with inflammatory bowel diseases (IBD) in pre-pregnancy, pregancy and loctation. METHODS: The clinical data of pregnancy complicated with IBD in Department of Obstetrics and Gynecology of Peking University Third Hospital and deli-very from September 2011 to June 2022 were collected. The clinical characteristics of the patients were analyzed retrospectively. According to the state of diseases during pre-pregnancy, pregnancy and lactation, the patients were divided into active and remission group, and the two groups were compared interms of pre-pregnancy counseling, nutritional status, pregnancy and delivery complications, gestational week, mode of delivery, and neonatal outcome. RESULTS: A total of 33 pregnant women with IBD were included in this study, of which 7 delivered a second child, for a total of 40 deliveries, with 36 natural pregnancies (90.0%) and 4 assisted reproductions (10.0%). Among the 40 cases, 21 cases (52.5%) were sustained in remission in pre-pregnancy, pregnancy and lactation, and 19 cases (47.5%) in disease activity, of which 8 cases (42.1%) were due to self-withdrawal of drugs or failure to take medicine regularly. Compared with the activity group, the disease remission group had a higher rate of pre-pregnancy counseling (57.1% vs. 15.8%, P=0.010), and higher levels of hemoglobin [(112.67±8.53) g/L vs. (102.84±5.23) g/L, P < 0.001], serum total protein [(66.58±6.34) g/L vs. (60.83±6.25) g/L, P=0.006], serum albumin [36.4 (35.1, 38.3) g/L vs. 34.3 (31.1, 35.6) g/L, P=0.006], serum calcium [(2.25±0.10) µmol/L vs. (2.13±0.15) µmol/L, P=0.004], but a lower incidence of gestational hypertensive disorders (0 vs. 31.6%, P=0.007). In 40 deliveries, there were 27 cases of vaginal delivery (67.5%), 13 cases of cesarean section (32.5%). The analysis of neonatal outcomes showed 38 full-term deliveries and 2 preterm deliveries; 1 case of macrosomia, 1 case of small-for-gestational-age, 1 case of low birth weight and 3 cases of birth defects. There were 10 newborns admitted to neonatal intensive care unit, including 4 cases of neonatal infections and 2 cases of neonatal jaundice. CONCLUSION: Pre-pregnancy counseling and evaluation of IBD patients are very important, and good pregnancy outcomes can be obtained through careful management during pregnancy in the most of the patients.

Associations between short-term exposure of ambient particulate matter and hemodialysis patients death: A nationwide, longitudinal case-control study in China.

BACKGROUND: Long-term exposure to particulate air pollutants can lead to an increase in mortality of hemodialysis patients, but evidence of mortality risk with short-term exposure to ambient particulate matter is lacking. This study aimed to estimate the association of short-term exposure to ambient particulate matter across a wide range of concentrations with hemodialysis patients mortality. METHODS: We performed a time-stratified case-crossover study to estimate the association between short-term exposures to PM2.5 and PM10 and mortality of hemodialysis patients. The study included 18,114 hemodialysis death case from 279 hospitals in 41 cities since 2013. Daily particulate matter exposures were calculated by the inverse distance-weighted model based on each case's dialysis center address. Conditional logistic regression were implemented to quantify exposure-response associations. The sensitivity analysis mainly explored the lag effect of particulate matter. RESULTS: During the study period, there were 18,114 case days and 61,726 control days. Of all case and control days, average PM2.5 and PM10 levels were 43.98 µg/m3 and 70.86 µg/m3, respectively. Each short-term increase of 10 µg/m3 in PM2.5 and PM10 were statistically significantly associated with a relative increase of 1.07 % (95 % confidence interval [CI]: 0.99 % - 1.15 %) and 0.89 % (95 % CI: 0.84 % - 0.94 %) in daily mortality rate of hemodialysis patients, respectively. There was no evidence of a threshold in the exposure-response relationship. The mean of daily exposure on the same day of death and one-day prior (Lag 01 Day) was the most plausible exposure time window. CONCLUSIONS: This study confirms that short-term exposure to particulate matter leads to increased mortality in hemodialysis patients. Policy makers and public health practices have a clear and urgent opportunity to pass air quality control policies that care for hemodialysis populations and incorporate air quality into the daily medical management of hemodialysis patients.

A BINOL-phosphoric acid and metalloporphyrin derived chiral covalent organic framework for enantioselective α-benzylation of aldehydes.

The catalytic asymmetric α-benzylation of aldehydes represents a highly valuable reaction for organic synthesis. For example, the generated α-heteroarylmethyl aldehydes, such as (R)-2-methyl-3-(pyridin-4-yl)propanal ((R)-MPP), are an important class of synthons to access bioactive drugs and natural products. We report herein a new and facile synthetic approach for the asymmetric intermolecular α-benzylation of aldehydes with less sterically hindered alkyl halides using a multifunctional chiral covalent framework (CCOF) catalyst in a heterogeneous way. The integration of chiral BINOL-phosphoric acid and Cu(ii)-porphyrin modules into a single COF framework endows the obtained (R)-CuTAPBP-COF with concomitant Brønsted and Lewis acidic sites, robust chiral confinement space, and visible-light induced photothermal conversion. These features allow it to highly promote the intermolecular asymmetric α-benzylation of aldehydes via visible-light induced photothermal conversion. Notably, this light-induced thermally driven reaction can effectively proceed under natural sunlight irradiation. In addition, this reaction can be easily extended to a gram-scale level, and its generality is ascertained by asymmetric α-benzylation reactions on various substituted aldehydes and alkyl bromides.

Construction of acid-base bifunctional covalent organic frameworks via Doebner reaction for catalysing cascade reaction.

We report herein a series of quinoline-4-carboxylic acid linked COFs via the multicomponent one-pot in situ Doebner reaction. The obtained acid-base bifunctional COFs are chemically stable and can highly promote one-pot cascade deacetalization-Knoevenagel condensation reaction in a heterogeneous way under solvent-free conditions.

Homochiral Covalent Organic Framework for Catalytic Asymmetric Synthesis of a Drug Intermediate.

(S)-2-(2-Chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetonitrile ((S)-CIK) is a key intermediate in the synthesis of (S)-clopidogrel, which is one of the most saleable worldwide antiplatelet and antithrombotic drugs. We show herein a facile method for the direct synthesis of (S)-CIK via Strecker reaction using a homochiral covalent framework catalyst in a heterogeneous way. The asymmetric synthesis involves a photothermal-conversion-triggered, thermally driven reaction which affords (S)-CIK in 98% yield with 94% enantiomeric excess under visible-light irradiation. Furthermore, the above approach is readily extended to a gram-scale level on a fixed-bed continuous-flow model reactor. The potential utility of this strategy is highlighted by the preparation of many more other types of chiral drugs and drug intermediates in a green and facile way.

Homochiral Covalent Organic Frameworks for Asymmetric Catalysis.

Owing to their permanent porosity, highly ordered and extended structure, good chemical stability, and tunability, covalent organic frameworks (COFs) have emerged as a new type of organic materials that can offer various applications in different fields. Benefiting from the huge database of organic reactions, the required functionality of COFs can be readily achieved by modification of the corresponding organic functional groups on either polymerizable monomers or established COF frameworks. This striking feature allows homochiral covalent organic frameworks (HCCOFs) to be reasonably designed and synthesized, as well as their use as a unique platform to fabricate asymmetric catalysts. This contribution provides an overview of new progress in HCCOF-based asymmetric catalysis, including design, synthesis, and their application in asymmetric organic synthesis. Moreover, major challenges and developing trends in this field are also discussed. It is anticipated that this review article will provide some new insights into HCCOFs for heterogeneous asymmetric catalysis and help to encourage further contributions in this young but promising field.

Construction of Covalent Organic Frameworks via Three-Component One-Pot Strecker and Povarov Reactions.

Postsynthetic modification (PSM) has been demonstrated to be a powerful method for achieving new covalent organic frameworks (COFs) via single-step or multistep organic functional group transformations on established COF frameworks. PSM, however, might sometimes lead to collapse of the COF framework, decreases in crystallinity, or low postsynthetic yield due to the inherent limit of solid-state synthesis. Herein we report, for the first time, a new synthetic strategy that can generate new COFs via multicomponent one-pot in situ reactions. In total, 12 α-aminonitrile- and quinoline-linked COFs with high crystallinity and permanent porosity are successfully achieved by three-component one-pot in situ Strecker and Povarov reactions under solvothermal conditions in high yields. The obtained COFs feature the same structures as those obtained from the stepwise PSM approach on an established imine-linked COF. This in situ multicomponent assembly strategy, as a synthetic methodology parallel to PSM, might open a new route for constructing COFs that is not possible under PSM conditions.

Photothermal conversion triggered thermal asymmetric catalysis within metal nanoparticles loaded homochiral covalent organic framework.

For seeking high enantiopurity, the previously reported thermal asymmetric catalysis is usually carried out at low temperature sometimes with limited yield, that is, the high enantiomeric excess (ee) usually at the cost of high yield. Thus, the achieving both high stereoselectivity and yield is an enormous challenge. We report herein two metal nanoparticle (M NP)-loaded and porphyrin-containing homochiral covalent organic framework (CCOF)-based composite catalysts, and their application in the thermally-driven asymmetric one-pot Henry and A3-coupling reactions. All the reactions are conducted at elevated temperatures with both excellent stereoselectivity and yield which resulted from the synergy of CCOF confinement effect and M NP catalytic activation. Notably, the needed thermal energy for the asymmetric reactions herein is derived from the photothermal conversion via porphyrin-based CCOF upon irradiation with visible light. Remarkably, the CCOF confinement effect can be effectively maintained up to 100 °C for the asymmetric one-pot Henry and A3-coupling reactions herein.

Homochiral BINAPDA-Zr-MOF for Heterogeneous Asymmetric Cyanosilylation of Aldehydes.

A new homochiral BINAPDA-Zr-MOF was prepared by a new chiral organic linker of (R)-4,4'-(6,6'-dichloro-2,2'-diethoxyl-[1,1'-binaphthalene]-4,4'-diyl)dibenzoic acid (R-L) and ZrCl4 under solvothermal conditions. Its structure was determined by Pawley refinement on the basis of the measured PXRD pattern determined for BINAPDA-Zr-MOF, and it showed that the obtained chiral MOF crystallized in the F23 space group with the same topological structure as that of UiO-66. The obtained BINAPDA-Zr-MOF can be a very active catalyst to catalyze aldehyde cyanosilylation. In addition, the chiral BINAPDA-Zr-MOF was a typical solid catalyst, which was proved by a hot leaching test; moreover, it could be reused at least five times without loss of its catalytic activity and enantioselectivity.

Understanding the gut-kidney axis among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition.

AIMS: Type 2 diabetes mellitus (T2DM) has a rising prevalence and gut microbiota involvement is increasingly recognized. Diabetic nephropathy (DN) is a major complication of T2DM. The aim of the study was to understand the gut-kidney axis by an analysis of gut microbiota composition among biopsy-proven DN, T2DM without kidney disease, and healthy control. METHODS: Fecal samples were collected from 14 DNs, 14 age/gender-matched T2DMs without renal diseases (DM), 14 age and gender-matched healthy controls (HC) and household contacts (HH) of DM group. The microbiota composition was analyzed by 16sRNA microbial profiling approach. RESULTS: Substantial differences were found in the richness of gut microbiota and the variation of bacteria population in DM compared to HC, and DN compared to DM, respectively. DM could be accurately distinguished from age/gender-matched healthy controls by the variable of genus g_Prevotella_9 (AUC = 0.9), and DN patients could be accurately distinguished from age/gender-matched DM by the variables of two genera (g_Escherichia-Shigella and g_Prevotella_9, AUC = 0.86). The microbiota composition of HH group was close to that of HC group, and was different from DM group. Under the same diet, DM could be more accurately detected by the same genus (g_Prevotella_9, AUC = 0.92). CONCLUSION: Gut microbiota composition was explored to be related to the occurrence of biopsy-proven DN from DM. DM could be distinguished from HC by detecting g_Prevotella_9 level in feces, while DN was different from DM by the variables of g_Escherichia-Shigella and g_Prevotella_9, which potentially contributed to the physiopathological diagnosis of DN from DM.

Analysis of serum metabolomics among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls.

Type 2 diabetes mellitus (T2DM) has a rising prevalence and diabetic nephropathy (DN) is a major complication of T2DM. Metabolomics could provide novel insights into the pathogenesis, so we aimed to explore serum metabolomic profiles from DN to T2DM. Serum samples were collected from 14 biopsy-proven DNs, 14 age/gender-matched T2DMs without renal diseases (DM), 14 age/gender-matched healthy controls (CTRL) and household contacts of DM group (HH). Serum metabolomics was analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC/MS) assays. There were a total of 1470 metabolites identified from all serum samples. 45 metabolites with significantly different intensity were found between DN and DM, e.g., biliverdin and taurine were reduced while l-arginine was increased in DN comparing to DM. DN could be distinguished from age/gender matched DM patients by l-arginine (AUC = 0.824) or taurine levels (AUC = 0.789). The metabolic pathways affected by metabolite distinctions between DN and DM also existed, among which taurine and hypotaurine metabolism exhibited the highest pathway impact. l-Methionine, deethylatrazine, l-tryptophan and fumaric acid were reduced in DM comparing with those of CTRL, but had no different intensity in DM and HH groups. The changes were demonstrated in the metabolomic profiles of biopsy-proven DN compared to DM. Biopsy-proven DN patients could be distinguished from age/gender matched DM by l-arginine or taurine levels in serum metabolomic profiles. Taurine and hypotaurine metabolism pathway had the highest impact in pathway set enrichment analysis, which potentially affected the pathogenesis of DN from T2DM.

Cu3L2 metal-organic cages for A3-coupling reactions: reversible coordination interaction triggered homogeneous catalysis and heterogeneous recovery.

The reported Cu(ii) metal-organic cage (Cu3L2, 1) can be a highly active reusable catalyst to homogeneously catalyze the A3-coupling reaction in CHCl3 and can be heterogeneously recovered by simply adding 1,4-dioxane via formation of the insoluble metal-organic framework (Cu3L2(1,4-dioxane)1.5, 2).

Ru Nanoparticles-Loaded Covalent Organic Framework for Solvent-Free One-Pot Tandem Reactions in Air.

Condensation of benzene-1,3,5-tricarbohydrazide with benzene-1,4-dicarboxaldehyde generated a new covalent organic framework, COF-ASB (1), in which the organic units are held together via hydrazone linkage to form porous frameworks. COF-ASB (1) is highly crystalline and displays good chemical and thermal stability and is permanently porous. In addition, 1 can be an ideal support to load Ru nanoparticles (Ru NPs) to generate Ru@COF-ASB (2). The obtained composite material is able to highly promote one-pot tandem synthesis of imine products from benzyl alcohols and corresponding amines under solvent-free conditions in air.

Dual Heterogeneous Catalyst Pd-Au@Mn(II)-MOF for One-Pot Tandem Synthesis of Imines from Alcohols and Amines.

A new Mn(II) metal-organic framework (MOF) 1 was synthesized by the combination of 4,4,4-trifluoro-1-(4-(pyridin-4-yl)phenyl)butane-1,3-dione (L) and Mn(OAc)2 in solution. 1 features a threefold-interpenetrating NbO net containing honeycomb-like channels, in which the opposite Mn(II)···Mn(II) distance is 23.5075(10) Å. Furthermore, 1 can be an ideal platform to support Pd-Au bimetallic alloy nanoparticles to generate a composite catalytic system of Pd-Au@Mn(II)-MOF (2). 2 can be a highly active bifunctional heterogeneous catalyst for the one-pot tandem synthesis of imines from benzyl alcohols and anilines and from benzyl alcohols and benzylamines.

Au@Cu(II)-MOF: Highly Efficient Bifunctional Heterogeneous Catalyst for Successive Oxidation-Condensation Reactions.

A new composite Au@Cu(II)-MOF catalyst has been synthesized via solution impregnation and full characterized by HRTEM, SEM-EDS, XRD, gas adsorption-desorption, XPS, and ICP analysis. It has been shown here that the Cu(II)-framework can be a useful platform to stabilize and support gold nanoparticles (Au NPs). The obtained Au@Cu(II)-MOF exhibits a bifunctional catalytic behavior and is able to promote selective aerobic benzyl alcohol oxidation-Knoevenagel condensation in a stepwise way.

Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.

In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system.