Sesquiterpenoids and Cytochalasins with Immunosuppressive Activity from Sonchus wightianus.

The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1-7) and one cytochalasin (8), along with five known guaianes (9-13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C-8 and/or C-15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X-ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.

Construction of iron metabolism-related prognostic features of gastric cancer based on RNA sequencing and TCGA database.

BACKGROUND: Researches have manifested that the disorder of iron metabolism is participated in Gastric cancer (GC), but whether iron metabolism-relevant genes (IMRGs) is related to the survival outcome of GC remain unknown. METHODS: Eleven tumor as well as nine adjacent normal tissues from GC patients were underwent mRNA sequencing, and the The Cancer Genome Atlas Stomach Cancer (TCGA-STAD) datasets were acquired from the TCGA database. Cox analyses and least absolute shrinkage and selection operator (LASSO) regression were applied to build a IMRGs signature. The relationship between signature genes and the infiltration profiling of 24 immune cells were investigated using single-sample GSEA (ssGSEA). Meanwhile, the potential biological significance, genes that act synergistically with signature genes, and the upstream regulatory targets were predicted. Finally, the abundance of the signature genes were measured via the quantitative real-time PCR (qRT-PCR). RESULTS: A IMRGs signature was constructed according to the expression and corresponding coefficient of DOHH, P4HA3 and MMP1 (The Schoenfeld individual test showed risk score was not significant with P values = 0.83). The prognostic outcome of patients in the high-risk group was terrible (p < 0.05). Receiver operating characteristic (ROC) curves confirmed that the IMRGs signature presented good efficiency for predicting GC prognosis (AUC > 0.6). The nomogram was performed well for clinical utilize (C-index = 0.60), and the MMP1 expression significantly increased in the cohorts at age > 60 and Stage II-IV (p < 0.05). The positive correlation of P4HA3 and MMP1 expression as well as the negative correlation of DOHH expression with risk score (p < 0.0001) and worse prognosis (p < 0.05) were detected as well. Furthermore, 11 differential immune cells were associated with these signature genes (most p < 0.01). Finally, qRT-PCR revealed that the abundance of DOHH, P4HA3 and MMP1 were high in tumor cases, indicating the complex mechanism between the high expression of DOHH as a protective factor and the high expression of P4HA3 and MMP1 as the risk factors in the development of GC. CONCLUSION: An iron metabolism-related signature was constructed and has significant values for foretelling the OS of GC.

Gut microbiota trajectory in ß-thalassemia major children who underwent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The gut microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) changes, leading to complications such as acute graft-versus-host disease (GVHD). This study aimed to evaluate the human microbiota composition before and after HSCT in ß-thalassemia major (ß-TM) children. METHOD: Twenty-two ß-TM children who received allo-HSCT between December 2018 and March 2020 were enrolled. They were followed up for more than 100 days after HSCT, and their gut microbiota information and disease data were recorded at five-time points. RESULTS: The dominant bacteria were Bacteroidetes and Firmicutes at the phylum level and Lachnospiraceae at the family level before and after HSCT. In the differential analysis, Ruminococcaceae constantly decreased after HSCT. Besides, Rothia mucilaginosa was the most abundant 2 months after HSCT compared to before it. Additionally, GVHD patients presented decreased levels of Bacteroidetes compared to those without GVHD. Moreover, Blautia levels significantly decreased in critically ill GVHD patients. CONCLUSION: The gut microbiota of the 22 ß-TM children showed a clear trend of destruction and reconstruction within 100 days after HSCT. The extra-oral infections and inflammations of Rothia mucilaginosa, a Gram-positive bacterium of the normal oropharyngeal tract microbiota, might play an important role in the recovery process of HSCT. Finally, decreased Bacteroidetes levels were associated with GVHD onset.

Weight progression and adherence to weight gain target in women with vs. without gestational diabetes: a retrospective cohort study.

BACKGROUND: Weight management has been an important component of the service in obstetric care offered to pregnant women. Current gestational weight gain recommendations were primarily for the general obstetric population, raising concern about the applicability to women with gestational diabetes mellitus (GDM). We aimed to assess the difference in weight progression and adherence to the recommended gestational weight gain targets between women with gestational diabetes mellitus (GDM) and women with normal glucose tolerance (NGT). METHODS: This was a hospital-based retrospective study of 56,616 pregnant women (9,430 GDM women and 47,186 NGT women) from Guangzhou between 2017 and 2021. The average change in weight progression was estimated based on serial weight measurements throughout pregnancy, using a mixed effects model with a random intercept to account for repeated measures of the same individual. RESULTS: Women with GDM gained less weight (12.07 [SD 5.20] kg) than women with NGT (14.04 [SD 5.04] kg) throughout pregnancy. Before OGTT, a small difference was observed in the average change in weight progression between the two groups (GDM, 0.44 kg/week vs. NGT, 0.45 kg/week, p < 0.001), however, this gap widened significantly after the test (0.34 vs. 0.50 kg/week, p < 0.001). GDM individuals were identified with an approximately 4-fold increased proportion of insufficient weight gain (41.1% vs. 10.4%) and a 2-fold decreased proportion of excessive weight gain (22.6% vs. 54.2%) compared to NGT individuals. These results were consistently observed across different BMI categories, including underweight (insufficient: 52.7% vs. 19.9%; excessive: 15.6% vs. 35.3%), normal weight (insufficient 38.2% vs. 7.4%; excessive: 22.2% vs. 57.3%), and overweight/obese (insufficient: 43.1% vs. 9.8%; excessive: 30.1% vs. 68.8%). CONCLUSION: Weight progression varied significantly between GDM and NGT individuals, resulting in a substantial difference in identifying insufficient and excessive weight gain between the two groups under current gestational weight gain guidelines.

Weight gain rate in the second and third trimesters and fetal growth in women with gestational diabetes mellitus: a retrospective cohort study.

BACKGROUND: Controversial evidence regarding the applicability of the IOM's gestational weight gain (GWG) targets for women with gestational diabetes mellitus (GDM) has been reported. However, little is known about the weight gain rate (WGR) during the second and third trimesters. Moreover, previous studies failed to assess the effect modification of pre-pregnancy BMI because of the limited sample size. Therefore, we aimed to assess the applicability of the IOM recommendation for the WGR in women with GDM in different pre-pregnancy BMI categories. METHODS: We conducted this retrospective cohort study of 5275 women with GDM who delivered at Guangzhou Women and Children's Medical Center (GWCMC) between January 2017 and January 2021. Demographic and clinical information was collected from the electronic medical record system. The primary exposure was the WGR in the late second and third trimesters; they were classified as below, within, and above the IOM standard. The outcomes were fetal growth indicators, including large-for-gestational-age (LGA), macrosomia, small-for-gestational-age (SGA), and low birth weight (LBW). The associations between the WGR and such outcomes were assessed using multiple logistic regression. RESULTS: A WGR below the IOM standard was associated with the decreased odds of LGA (adjusted OR 0.74; 95% CI 0.49-1.13) and macrosomia (adjusted OR 0.54, 95% CI 0.32-0.92) for women with GDM in the normal weight BMI class. Such decreases were observed greater for women with GDM in the overweight/obese class, with adjusted ORs of 0.34 (95% CI 0.09-0.88) for LGA and 0.31 (95% CI 0.01-0.84) for macrosomia, respectively. No significant difference was observed in the odds ratios of SGA and LBW across the different WGR groups. CONCLUSION: LGA and macrosomia are the main outcomes associated with the WGR in the late second and third trimesters, and a WGR below the IOM standard was associated with a decreased odds of such outcomes compared with a WGR within the IOM standard in women with GDM in the normal weight and overweight/obese classes. Our findings suggest that a stricter WGR target than that of the current IOM standard may be more beneficial for women with GDM.

IL-37bΔ1-45 suppresses the migration and invasion of endometrial cancer cells by targeting the Rac1/NF-κB/MMP2 signal pathway.

Endometrial carcinoma is one of the most common malignancies in the female reproductive system. Interleukin-37 (IL-37) is a newly discovered anti-inflammatory factor belonging to the IL-1 family. IL-37 has five different isoforms, and IL-37b is the most biologically functional subtype. In recent years, the protective roles of IL-37 in different cancers, including lung and liver cancers, have been successively reported. IL-37 also plays an important role in some gynecological diseases such as endometriosis, adenomyosis, and cervical cancer. However, the role and mechanism of IL-37b, especially the mature form of IL-37b, in endometrial carcinoma have not been elucidated. The present study demonstrated that IL-37 protein was downregulated in endometrial carcinoma cells compared with the control endometrium. IL-37b did not affect the proliferation and colony-forming ability of endometrial cancer cells. A mature form of IL-37b (IL-37bΔ1-45) effectively suppressed the migration and invasion of endometrial cancer cells by decreasing the expression of matrix metalloproteinase 2 (MMP2) via Rac1/NF-κB signal pathway. However, it did not affect epithelial-mesenchymal transition (EMT) or filamentous actin (F-actin) depolymerization of endometrial cancer cells. IL-37bΔ1-45 attenuated tumor metastasis in a peritoneal metastatic xenograft model of endometrial cancer. To sum up, these results suggested IL-37b could be involved in the pathogenesis of endometrial carcinoma and provide a novel target for the diagnosis and treatment of endometrial carcinoma.

TIPE2 inhibits the migration and invasion of endometrial cells by targeting ß-catenin to reverse epithelial-mesenchymal transition.

STUDY QUESTION: Do changes in tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) levels in endometrium of patients with adenomyosis alter the proliferation, migration and invasion ability of endometrial cells? SUMMARY ANSWER: TIPE2 expression levels were low in eutopic and ectopic endometrium of adenomyosis patients, and TIPE2 inhibited the migration and invasion of endometrial cells, mainly by targeting ß-catenin, to reverse the epithelial-mesenchymal transition (EMT). WHAT IS KNOWN ALREADY: Adenomyosis is a benign disease, but it has some pathophysiological characteristics similar to the malignant tumor. TIPE2 is a novel negative immune regulatory molecule, and it also participates in the development of malignant tumors. STUDY DESIGN, SIZE, DURATION: Control endometrium (n = 48 women with non-endometrial diseases) and eutopic/ectopic endometrium from patients with adenomyosis (n = 50), human endometrial cancer cell lines, and primary endometrial cells from the eutopic endometrium of adenomyosis patients were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression level of TIPE2 mRNA and protein in the eutopic/ectopic endometrial tissues of adenomyosis patients and control endometrium was determined by quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of endometrial cell lines and primary adenomyotic endometrial cells were determined using a cell counting kit-8, 5-ethynyl-2'-deoxyuridine assay, colony-forming assay, transwell migration assay and matrigel invasion assay. The expression of EMT-related markers and signal molecules was detected by western blot. The interaction between TIPE2 and ß-catenin was detected by co-immunoprecipitation and laser confocal microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The mRNA and protein expression levels of TIPE2 in the eutopic and ectopic endometrial tissues of adenomyosis patients were significantly downregulated compared with the control endometrium (P Ë‚ 0.01). TIPE2 could bind to ß-catenin and inhibit the nuclear translocation of ß-catenin, downregulate the expression of stromal cell markers, upregulate the expression of glandular epithelial cell markers, decrease the occurrence of epithelial-mesenchymal transition (EMT) and suppress the migration and invasion of endometrial cells (P Ë‚ 0.01). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, the experiments were performed only in eutopic and ectopic endometrial tissues, endometrial cancer cell lines and primary adenomyotic endometrial cells. A mouse model of adenomyosis will be constructed to detect the effects of TIPE2 in vivo. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest that TIPE2 is involved in the development of adenomyosis, which provides a potential new diagnostic and therapeutic strategy for the treatment of adenomyosis. STUDY FUNDINGS/COMPETING INTEREST(S): This present study was supported by grants from the National Natural Science Foundation of China (81471437, 81771554), Natural Science Foundation of Shandong (ZR2018MH013), Science and technology development plan provided by Health and Family Planning Committee in Shandong (2014-25). The authors declare that they have no conflicts of interest.

[Expert consensus on nutritional management of preterm infants with bronchopulmonary dysplasia].

Inadequate nutrition supply in the early stage after birth is a risk factor for the development of bronchopulmonary dysplasia (BPD) in preterm infants, and it is also closely associated with the progression and clinical outcome of BPD. Optimized nutritional support is of great importance to reduce the incidence and severity of BPD and promote lung development and neurological prognosis. Based on the relevant studies in China and overseas, the expert consensus on BPD nutrition management is developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. The consensus includes the following seven aspects: the importance of nutrition in BPD, fluid intake, energy intake, enteral nutrition, parenteral nutrition, post-discharge nutrition, and nutrition monitoring and evaluation.

Probing the function of protein farnesyltransferase in Tripterygium wilfordii.

KEY MESSAGE: We found two subunits FTase/GGTaseI-α and FTase-ß formed a heterodimer to transfer a farnesyl group from FPP to protein N-dansyl-GCVLS, confirming they are responsible for protein farnesylation in planta. Tripterygium wilfordii is a medicinal plant with a broad spectrum of anti-inflammatory, immunosuppressive and anti-cancer activities. Recently, a number of studies have focused on investigating the biosynthetic pathways of its bioactive compounds, whereas little attention has been paid to the enzymes which play important roles in regulating diverse developmental processes of T. wilfordii. In this study, we report for the first time the identification and characterization of two subunits of farnesyltransferase (FTase), farnesyltransferase/geranylgeranyltransferase I-α (TwFTase/GGTase I-α) and farnesyltransferase-ß (TwFTase-ß), in this important medicinal plant. Cell-free in vivo assays, yeast two-hybrid (Y2H) and pull-down assays showed that the two subunits interact with each other to form a heterodimer to perform the role of specifically transferring a farnesyl group from FPP to the CAAX-box protein N-dansyl-GCVLS. Furthermore, we discovered that the two subunits had the same cytoplasmic localization pattern and displayed the same tissue expression pattern. These results indicated that we identified a functional TwFTase enzyme which contains two functionally complementary subunits TwFTase/GGTase I-α and TwFTase-ß, which provides us promising genetic targets to construct transgenic plants or screen for more adaptable T. wilfordii mutants, which are able to survive in changing environments.

Osteopontin Levels in Human Milk Vary Across Countries and Within Lactation Period: Data From a Multicenter Study.

OBJECTIVES: Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers. METHODS: At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively. RESULTS: A total of 829 milk samples from 629 women were included. When delivering the first sample, mean maternal age was 31.4 years (SD 4.0), and median infant age was 13.4 weeks (interquartile range 4.6-17.9). The median OPN concentration varied across sites; from 99.7 mg/L in Danish, 185.0 mg/L in Japanese, 216.2 mg/L in Korean to 266.2 mg/L in Chinese mothers (P < 0.001), corresponding to 1.3%, 2.4%, 1.8% and 2.7% of the total protein content (OPN/protein%) (P < 0.05), respectively. Based on 75 Chinese and 33 Japanese mothers delivering more than 1 sample, multilevel (mixed model) linear regression analysis showed a decrease in OPN concentration with infant age (ß = (-11.3), 95% confidence interval (CI) = (-13.9) to (-8.8) and ß = (-2.1), 95% CI = (-3.2) to (-0.9), respectively). CONCLUSIONS: In this large multicenter study, we observed statistically significant differences in the OPN concentration and the OPN/protein% in human milk samples between countries. Based on mothers delivering more than 1 sample, a significant decrease within the lactation period was observed.

The Important Role of the Byproduct Triphenylphosphine Oxide in the Magnesium(II)-Catalyzed Enantioselective Reaction of Hemiacetals and Phosphorus Ylides.

By employing a simple in situ generated magnesium catalyst, a direct asymmetric reaction between hemiacetals and phosphorus ylides was achieved through a tandem Wittig-oxa-Michael reaction sequence. Enantioenriched chromans, isochromans, and tetrahydropyrans were obtained in good chemical yields, and (-)-erythrococcamide B was synthesized in enantioenriched form. The byproduct triphenylphosphine oxide was identified as a necessary additive for this process.

An Efficient Nickel-Catalyzed Asymmetric Oxazole-Forming Ugi-Type Reaction for the Synthesis of Chiral Aryl-Substituted THIQ Rings.

A nickel-catalyzed asymmetric oxazole-forming Ugi reaction of C,N-cyclic azomethine imines and isonitriles is disclosed. The reported protocol proceeds smoothly, and gives the corresponding adducts, which contain two important pharmaceutically active ring-systems (tetrahydroquinoline and oxazole rings), in good yields and excellent enantioselectivities by employing an easily accessible chiral diamine as a ligand. This simple and efficient strategy provides easy access to a series of C1-substituted aryl tetrahydroisoquinolines.

MgII -Catalyzed Desymmetrization Reaction of meso-Aziridines with Hydroxylamines: Synthesis of Novel Chiral 1,2-Diamine Skeletons.

A MgII -catalyzed desymmetrization reaction of meso-aziridines with hydroxylamines has been disclosed for the first time. A series of novel chiral 1,2-diamine skeletons were obtained in good yields and enantioselectivities. The reaction employed magnesium catalysis generated in situ from a simple oxazoline-OH chiral ligand. Obviously, the diverse structures of the obtained chiral 1,2-diamine compounds could allow them to be potential chiral ligands in future catalytic asymmetric synthesis studies.

Improvement of Left Ventricular Remodelling by Inhibition of NF-κB in a Rat Model of Myocardial Infarction.

BACKGROUND: To investigate the effects of inhibition of NF-κB activation on left ventricular (LV) remodelling in a rat model of myocardial infarction (MI). METHODS: The acute MI model was established by ligation of left anterior descending coronary artery. Pyrrolidine dithiocarbamate (PDTC) (20mg/kg, Qd) was administered intraperitoneally to inhibit NF-κB activation. Eight weeks later, the cardiac structure and LV ejection fraction were assessed with echocardiography. The rat body, heart, and LV weights were measured to calculate LV mass indices. Activation of NF-κB in non-infarcted myocardium was detected by a TransAM NF-κB p65 Transcription Factor Assay Kit. Cardiac collagen volume fraction was evaluated by Masson staining. RESULTS: Eight weeks after the MI model was established, the LV posterior wall thickness in PDTC and MI group was 1.75±0.07mm and 1.85±0.07mm respectively (p<0.05). The LV mass index in the PDTC group (2.53±0.09) was lower than in the MI group (2.65±0.08, p<0.05). The LVEF in the PDTC group (63.89%±4.21%) was higher than in the MI group (42.73%±8.94%, p<0.05). The interstitial collagen deposition in the non-infarcted myocardium in the PDTC group was less than in the MI group (7.25%±1.88% vs. 10.09%±2.19%, p<0.05). CONCLUSION: Inhibition of activation of NF-κB may result in improvement of myocardial remodelling after myocardial infarction, which is possibly attributable to reduced collagen deposition in non-infarcted areas.

Catalytic Asymmetric Inverse-Electron-Demand 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Azlactones: Access to Chiral Tricyclic Tetrahydroisoquinolines.

Reported herein is a bifunctional-organocatalyst-mediated enantioselective inverse-electron-demand 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines with azlactones. The strategy provides concise access to enantioenriched C1-substituted tetrahydroisoquinolines featuring a pyrazolidinone scaffold. Moreover, the scalability and practical utility of this protocol was well demonstrated by employing a gram-scale reaction and some representative transformations.

[Research advances in breastfeeding].

Human breast milk is the most natural and ideal food for the baby. Breastfeeding provides benefits for maternal and child health, child immune function, growth and development, and society. The operation of human milk bank and the use of donor human milk undoubtedly provides a new way of nutrition support for the preterm infants without their own mother's milk and a new kind of treatment for other diseases. Present research on the composition of breast milk focuses on the variety and quantity of proteins, bioactive substances, probiotics and cell population.Future research may focus on the bioactive substances, the mechanism of regulation and effect of cell population, the application of probiotics and the clinical application of donor human milk.

Construction of Vicinal Tetrasubstituted Stereocenters with a C-F Bond through a Catalytic Enantioselective Detrifluoroacetylative Mannich Reaction.

An efficient asymmetric detrifluoroacetylative Mannich reaction of 2-fluoro-1,3-diketones/hydrates with isatin-derived ketimines catalyzed by a chiral copper(II)-diamine complex has been realized. The reaction afforded a series of 3-substituted 3-amino-2-oxindoles bearing fluorine-containing vicinal tetrasubstituted stereocenters in high yields (up to 99%) with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 94% ee).

Magnesium complexes as highly effective catalysts for conjugate cyanation of α,ß-unsaturated amides and ketones.

Asymmetric cyanation of trimethylsilyl cyanide (TMSCN) with α,ß-unsaturated amides and ketones, respectively, catalyzed by bifunctional mononuclear 1,1'-bi-2-naphthol (BINOL)-Mg and binuclear bis(prophenol)-Mg catalysts was realized. A series of synthetically important 1,4-cyano products were obtained with good to high enantioselectivities (up to 97 % ee).

[Medical application of breast milk banks].

The history of breast milk banks is over 100 years. Most of the milk banks were closed because of HIV in the 80's. But more and more milk banks are re-opening and new ones are being established as the composition and superiority of breast milk are recognized again. The Human Milk Banking Association of North America and European Milk Bank Association have been set up and they have established and revised the standards and guidelines of breast milk banks. There is no doubt of the clinical effects of donor human milk on preterm infants worldwide. The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommended that the preterm infants should use donor human milk when their own mothers' milk is not enough. The first breast milk bank was set up in China in 2013, and its clinical and social significance is worthy of further study.

Enantioselective synthesis of [4]helicenes by organocatalyzed intermolecular C-H amination.

Catalytic asymmetric synthesis of helically chiral molecules has remained an outstanding challenge and witnessed fairly limited progress in the past decades. Current methods to construct such compounds almost entirely rely on catalytic enantiocontrolled fused-ring system extension. Herein, we report a direct terminal peri-functionalization strategy, which allows for efficient assembling of 1,12-disubstituted [4]carbohelicenes via an organocatalyzed enantioselective amination reaction of 2-hydroxybenzo[c]phenanthrene derivates with diazodicarboxamides. The key feature of this approach is that the stereochemical information of the catalyst could be transferred into not only the helix sense but also the remote C-N axial chirality of the products, thus enabling the synthesis of [4]- and [5]helicenes with both structural diversity and stereochemical complexity in good efficiency and excellent enantiocontrol. Besides, the large-scale preparations and representative transformations of the helical products further demonstrate the practicality of this protocol. Moreover, DFT calculations reveal that both the hydrogen bonds and the C-H---π interactions between the substrates and catalyst contribute to the ideal stereochemical control.