Macro-manufacturing robust and stable metal-organic framework beads for antibiotics removal from wastewater.

Metal-organic frameworks (MOFs) have shown great prospects in wastewater remediation. However, the easy aggregation, difficult separation and inferior reusability greatly limit their large-scale application. Herein, we proposed a facile, green and low-cost strategy to construct robust and stable MOF-based hydrogel beads (Fe-BTC-HBs) in a gram scale, and employed them to remove antibiotics from wastewater. As a result, the Fe-BTC-HBs demonstrated outstanding adsorption capacity for both ofloxacin (OFL) and tetracycline (TC) (281.17 mg/g for OFL and 223.60 mg/g for TC) under a near-neutral environment. The main adsorption mechanisms of OFL and TC were hydrogen bonding and π-π stacking interaction. Owing to its macroscopic granule and stable structure, Fe-BTC-HBs can be separated rapidly from wastewater after capturing antibiotics, and more than 85% adsorption capacity still remained after six cycles, while the powdered Fe-BTC only showed less than 6% recovery efficiency with massive weight loss (around 92%). In real industrial effluent, the adsorption performance of Fe-BTC-HBs toward two antibiotics exhibited negligible decreases (2.9% for OFL and 2.2% for TC) compared with that in corresponding solutions. Furthermore, Fe-BTC-HBs also had appealing economic and environmental benefit. Overall, the macro-manufactured MOF beads have the promising potential for the large-scale wastewater treatment.

Alexithymia and negative emotions among nursing students: a moderated mediation model.

Nursing students, who comprise a high percentage of China's college students, experience many psychological problems; however, few studies explored the mechanisms underlying these problems. This cross-sectional study explored the relationships and mechanisms of depression, anxiety, stress, and narrative disorders in senior nursing students. Questionnaires were administered to 380 senior nursing students in Hubei Province using the Sociodemographic Questionnaire, Toronto Alexithymia-20 Scale, Perceived Social Support Scale, 10-Item Connor-Davidson Resilience Scale, and Depression-Anxiety-Stress Scale. After controlling for sociodemographic variables, Hayes' PROCESS macros were used to test how psychological resilience moderates the relationships among narrative disorders, negative affect, and perceived social support. Bootstrap confidence intervals tested for indirect effects. Correlation analyses revealed that alexithymia was correlated significantly positively with depression-anxiety-stress (r = 0.57, 0.56, and 0.58, resp.) and significantly negatively with perceived social support (r = 0-0.46). Psychological resilience was correlated significantly negatively with alexithymia (r=-0.39) and depression-anxiety-stress (r=-0.31, -0.30, and-0.32, resp.) but significantly positively with perceived social support(r = 0.50). Perceived social support was correlated significantly negatively with depression-anxiety-stress (r=-0.33, -0.34, and - 0.42 resp.). Stress was correlated significantly positively with anxiety and depression (r = 0.81 and 0.77, resp.). Psychological resilience was a partial mediator between depression and dysphoria (ß=-0.08, p < 0.05). Dysphoria directly predicted anxiety (ß = 0.31) and stress (ß = 0.37); moreover,alexithymia predicted depression not only directly but also through the mediating effect of psychological resilience. Therefore, educators and clinical administrators must promote and recognise negative emotions among nursing students to help ensure the nursing workforce's stability.

Iatrogenic skin injuries in infants admitted to neonatal intensive care units: An investigation in 22 Chinese units.

OBJECTIVE: To investigate the incidence of iatrogenic skin injuries in neonates across 22 neonatal intensive care units (NICUs) in China. DESIGN: Prospective study. SETTING: 22 NICUs in China. PATIENTS: Infants admitted to NICU. INTERVENTIONS: None. MEASUREMENTS: The "Iatrogenic Skin Injuries Data Collection Form of infants" were used to collect the data during hospitalization. MAIN RESULTS: A total of 8126 neonates who were hospitalized in 22 tertiary hospitals across 15 provinces, cities, and autonomous regions of China between December 1, 2019 and January 31, 2020 were analyzed. Five hundred and twenty-one infants had iatrogenic skin injuries, including 250 with diaper dermatitis (47.98%), 70 with physicochemical factor-related skin lesions (PCFRSIs) (13.44%), 81 with medical device-related pressure injuries (MDRPIs) (15.55%), and 69 with medical adhesive-related skin injuries (MARSIs) (13.24%), accounting for 91% of the total number of iatrogenic injuries. Among these, diaper dermatitis was closely related to the skin and feeding status. Furthermore, the risk was higher among neonates who had skin damage upon admission or were already fully fed orally. The influencing factors of MDRPIs and MARSIs were similar. They were negatively associated with gestational age and birth weight, and were closely related to the presence of various tubes. CONCLUSIONS: Diaper dermatitis, PCFRSIs, MDRPIs, and MARSIs were the four common types of iatrogenic skin injuries in newborns. The various types of iatrogenic skin injuries were influenced by varying factors. Specialized nursing measurements can reduce the likelihood of these injuries.

Highly Efficient and Chemoselective Tandem Hydroformylation-Hydrogenation of Alkenes to Alcohols over g-CN Supported Bimetallic Rh and Co Nanoparticles Catalysts.

The objective of the tandem hydroformylation-hydrogenation of alkenes to corresponding alcohols was to design an efficient and stable heterogeneous catalyst. To this end, a series of novel heterogeneous graphitic carbon nitride (g-CN) supported bimetallic Rh-Co nanoparticle catalysts (Rh-Co/g-CN) were prepared and subsequently studied for this one-pot two-step reaction. The lamellar structure makes Rh and Co nanoparticles with diameters of <1 nm and 20 nm, respectively, homogeneously deposited on the surface of g-CN layers, exhibit remarkable conversion of styrene (99.9 %) and chemoselectivity for alcohol (87.8 %). More importantly, Co nanoparticles are found to play an important role in the improvement of the chemoselectivity for alcohol due to the formation of catalytic active species [HCo(CO)y ]. Besides the detailed investigation of the catalytic properties of Rh-Co/g-CN under different reaction conditions, the reuse of Rh-Co/g-CN was conducted for five times and no evident decrease in the activity and chemoselectivity was observed. Therefore, we expect that this work could offer an initial insight into g-CN-based heterogeneous catalyst on the tandem hydroformylation-hydrogenation reaction.

Designing dynamic groundwater management strategies through a composite groundwater vulnerability model: Integrating human-related parameters into the DRASTIC model using LightGBM regression and SHAP analysis.

Groundwater nitrate contamination has emerged as a pressing global concern. Given its potential for long-term impacts on aquifers, protective measures should primarily focus on prevention. Drawing on the theory of groundwater vulnerability (GV), the original DRASTIC model and parameters related to human activities are employed as inputs and integrated with the LightGBM regression algorithm to facilitate nitrate index (NI) prediction tasks. The SHAP analysis is conducted to effectively examine the contribution of parameters to the NI prediction and interpret the issue of parameter interactions. In addition, to mitigate the limitations of the intrinsic GV model, a composite nitrate index (CNI) is developed by linearly combining the DRASTIC index with the NI. The framework presented in this study provides adaptive strategies for managing groundwater resources over different time periods. A representative region for arid and semiarid climates, the Yinchuan region, is studied using the framework. As compared to 2012, the intrinsic GV index has changed spatially in 2022. Human activities have increased the influence of the nitrate concentration as shown by the Pearson correlation coefficient of -0.082 between the DRASTIC index and nitrate concentration. A significant increase in pollution levels was predicted by NI, ranging from -0.116 to 0.968. According to SHAP analysis, the significant increase in NI levels in 2022 was mainly due to high-value industrial and agricultural production. In 2022, 12.02% of the areas had an increase of at least 0.549 in the CNI. 42.1% of the areas were classified as moderate or high CNI levels. The farm was identified as a high-contributing source to nitrate pollution. The small-scale agricultural and livestock activities in non-urban areas also contribute to groundwater pollution. Dynamic groundwater management strategies need to be implemented in high-growth and high-level CNI areas.

Association between residential greenspace and mental health among cancer survivors in Shanghai, China.

BACKGROUND: Living near and enjoying visually green landscapes is associated with better mental health, but evidence focusing on vulnerable populations (such as cancer survivors) is sparse. The purpose of this study was to explore the association between residential greenspace and anxiety and depressive symptoms among cancer survivors in Shanghai, China. METHODS: In total, 4195 cancer survivors participated in this study from the 2022 Shanghai Cancer Patient Needs Survey. The estimation of residential greenspaces was based on Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI). The presence and severity of depressive and anxiety symptoms were assessed by using the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2). The relation between mental health and green space was assessed using the Generalized Additive Model (GAM) after controlling for relevant individual covariates and contextual characteristics. RESULTS: The prevalence of anxiety and depression in cancer survivors was 36.2% and 28.3% respectively. After multivariate adjustment, each increase in inter-quartile range (IQR) for NDVI in the 250 m buffer (NDVI-250m) was associated with a decrease in PHQ-2 score (△score (95%CI): 0.018 (-0.034, -0.002)) and GAD-2 score (△score (95%CI): 0.018 (-0.034, -0.002)), respectively. We observed that an increase in IQR for NDVI-250m was associated with a 3.3% (Odds ratio (OR) (95%CI):0.967 (0.943, 0.991)) reduction in anxiety symptoms. More pronounced greenspace-mental health effects were found among young adults (18-65 years) and participants living in suburban areas, compared to young people over 65 and those living in urban areas (P-interaction < 0.05). CONCLUSIONS: Higher levels of residential green space are associated with lower risk of depression and anxiety disorders. Our findings will fill the gap in the relationship between green space and mental health among cancer survivors in urban China, and provide new evidence for garden afforestation, community planning and policy-making. To better understand this association, more longitudinal studies are necessary to investigate the mechanisms involved.

Peripheral perfusion index in well newborns at 6 to 72 h of life at different altitudes: a multi-center study in China.

The purpose of this study is to obtain the reference range of peripheral perfusion index (PPI) of asymptomatic well newborns at 6 to 72 h of life at different altitudes. A population-based prospective cohort study was conducted in cities at different altitudes in China. Asymptomatic well newborns were enrolled consecutively from six hospitals with an altitude of 4 to 4200 m between February 1, 2020, and April 15, 2021. PPI was measured at 6, 12, 24, 48, and 72 h after birth on the right hand (pre-ductal) and either foot (post-ductal) using a Masimo SET Radical-7 oximeter. Fiftieth percentile reference curves of the pre- and post-ductal PPI values at 6-72 h after birth were generated using the Lambda Mu Sigma method. Linear mixed-effects regression was performed to determine the influence of different altitude levels on PPI values over different measurement time points. A total of 4257 asymptomatic well newborns were recruited for analysis. The median and quartile pre- and post-ductal PPI values at 6-72 h of life at different altitudes were 1.70 (1.20, 2.60) and 1.70 (1.10, 2.70) for all infants, 1.30 (1.10, 1.90) and 1.10 (0.88, 1.80) for infants at low altitude, 1.40 (1.00, 2.00) and 1.30 (0.99, 2.00) at mild altitudes, 1.90 (1.30, 2.50) and 1.80 (1.20, 2.70) at moderate altitudes, 1.80 (1.40, 3.50) and 2.20 (1.60, 4.30) for high altitudes, 3.20 (2.70, 3.70), and 3.10 (2.10, 3.30) for higher altitudes, respectively. Overall, both pre- and post-ductal PPI increased with altitude. The 50th percentile curves of pre- and post-ductal PPI values in well newborns at mild, low, moderate, and high altitudes were relatively similar, while the difference between the PPI curves of infants at higher altitudes and other altitudes was significantly different.  Conclusions: With the increase of altitude, pre- and post-ductal PPI of newborns increases. Our study obtained the PPI reference values of asymptomatic well newborns at 6 to 72 h after birth at different altitudes from 4 to ≥ 4000 m. What is Known: • Monitoring hemodynamics is very important to neonates. As an accurate and reliable hemodynamic monitoring index, PPI can detect irreversible damage caused by insufficient tissue perfusion and oxygenation early, directly, noninvasively, and continuously. What is New: • Our study obtained the PPI reference values of asymptomatic well newborns at 6 to 72 h after birth at different altitudes from 4 to ≥ 4000 m. With the increase of altitude, pre- and post-ductal PPI of newborns increase with statistical significance. Therefore, the values and disease thresholds of PPI for asymptomatic neonates should be modified according to altitudes.

The clinical experience of early skin-to-skin contact combined with non-nutritive comfort sucking in mothers of preterm infants: a qualitative study.

BACKGROUND: In most areas of China, mothers typically do not participate in early care of preterm infants in NICU. This study aims to examine the early experience of mothers of preterm infants participating in skin-to-skin contact combined with non-nutritive comfort sucking in China. METHODS: This qualitative research study used one-on-one, face-to-face, semi-structured in-depth interviews. Eighteen mothers who participated in early skin-to-skin contact combined with non-nutritive comfort sucking were interviewed in the NICU of a tertiary children's hospital in Shanghai between July and December 2020. Their experiences were analyzed using the inductive topic analysis method. RESULTS: Five themes about skin-to-skin contact combined with non-nutritive comfort sucking were identified, including alleviation of maternal anxiety and fear during mother infant separation, reshaping the maternal role, promotion of active breast pumping, enhances the mother's willingness to actively breast feed and building the maternal confidence in baby care. CONCLUSION: Skin-to-skin contact combined with non-nutritive comfort sucking in the NICU can not only enhance the identity and responsibility of the mother's role, but also provide non-nutritive sucking experience for promoting the establishment of oral feeding in preterm infants.

A nurse-inserted peripherally inserted central catheter program in general pediatrics: a single-center experience.

BACKGROUND: A peripherally inserted central catheter (PICC) with its tip preferably in the vena cava is essential in caring for patients with chronic conditions in general pediatrics. However, PICC-related complications are concerning and warrant further investigations. OBJECTIVES: To share the experience of a nurse-inserted peripherally inserted central catheters (PICC) program initiated in a general pediatric department. METHODS: A retrospective descriptive cohort study based on a prospectively collected database was conducted. All PICCs inserted in the departments of gastroenterology and pulmonology in a tertiary pediatric center from Dec. 2015 to Dec. 2019 were included in the study. Complications and risk factors were analyzed by comparing cases with and without complications. We also reported arm movements in correcting mal-positioned newly-inserted PICCs. RESULTS: There were 169 cases with a median (IQR) age of 42(6, 108) months who received PICC insertion during a 4-year period. Inflammatory bowel disease was the leading diagnosis accounting for 25.4% (43/169) of all cases. The overall complication rate was 16.4 per 1000 catheter days with malposition and occlusion as the two most common complications. Multivariate models performed by logistic regression demonstrated that young age [p = 0.004, OR (95%CI) = 0.987(0.978, 0.996)] and small PICC diameter (1.9Fr, p = 0.003, OR (95%CI) = 3.936(1.578, 9.818)] were risk factors for PICC complications. Correction of malpositioned catheters was attempted and all succeeded in 9 eligible cases by using arm movements. CONCLUSION: The nurse-inserted PICC program in general pediatrics is feasible with a low rate of complications. PICC tip malposition and occlusion were two major PICC-related complications when low age and small catheter lumina were major risk factors. Furtherly, arm manipulation potentially is an easy and effective approach for correcting malpositioned newly-inserted PICC catheters.

Psychological Journey and Coping Styles of Parents of Infants With Biliary Atresia: A Single-Center Qualitative Study.

BACKGROUND: Biliary atresia is a rare and serious neonatal disease that affects the quality of life of both infants and parents. There is currently limited literature on the experiences of parents with infants diagnosed with biliary atresia. PURPOSE: To explore the psychological journey and coping styles of parents of infants with biliary atresia in a single center in Shanghai, China. METHODS: A qualitative study design was used. Face-to-face and semistructured interviews were conducted with 10 parents of infants with biliary atresia. Colaizzi's method of data analysis was utilized, using NVivo 11.0 software. RESULTS: The psychological journey and coping styles of parents could be divided into 4 stages. Different themes were extracted at different stages: before diagnosis, parents experienced complex emotions and actively sought treatment; at the diagnosis stage, negative emotions dominated and parents convinced themselves to accept reality; in the postoperative stage, positive emotions, accepting reality, active response, and the need to learn to take care of their infant gradually appeared; and at the discharge stage, parents accepted the coexistence of positive and negative emotions and the variety of needs that emerged. IMPLICATIONS FOR PRACTICE: The findings of the study may help healthcare professionals identify and focus on the psychological needs of parents of infants with biliary atresia, leading them to implement effective coping strategies to increase the caregiving ability of parents. IMPLICATIONS FOR RESEARCH: Future research should explore the effects of supportive interventions for parents of infants with serious chronic illnesses.

[Latest Findings on the Suck-Swallow-Breathe Mechanism of Direct Breastfeeding From the Breast to an Infant]. / 母乳亲喂婴儿吸吮-吞咽-å‘¼å¸æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

A mother's breast milk is the best nourishing food for infants. No only does it provide sufficient nutrition, but it is also well suited to infants' immature digestive function, thus promoting their growth and organ maturation. A 6-month period of breastfeeding can provide infants with the necessary nutrients, energy, and fluids. The best feeding method is direct breastfeeding from the breast to an infant, yet the difficulties involved in breastfeeding should not be overlooked. Approximately 1/3 the mothers who are performing direct breastfeeding from the breast to an infant experience moderate or higher levels of feeding difficulties. Difficulties in direct breastfeeding from the breast to an infant can lead to decreased feeding efficiency, hamper the growth and development of infants, and affect the emotional communication between mothers and infants. At present, many relevant studies have focused on topics such as the mothers' psychology, family and social support, and the immature development of infants. However, little research has been done to investigate suck-swallow-breathe, a physiological mechanism that infants undertake during the process of direct breastfeeding from the breast to an infant. In this paper, we summarized published literature, research parameters, measurement instruments, and physical intervention methods of the suck-swallow-breathe mechanism in infants, aiming to facilitate the early identification of breastfeeding difficulties and the subsequently provision of early intervention measures and to promote the early identification of neurodevelopmental abnormalities and other developmental abnormalities in infants.

The effects of gestational diabetes mellitus with maternal age between 35 and 40 years on the metabolite profiles of plasma and urine.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35-40 years at early and late gestation. METHODS: Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). RESULTS: One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. CONCLUSION: This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35-40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.

Care practices and short-term clinical outcomes of very low birth weight infants in Yangtze River Delta in China.

BACKGROUND: Intensive care is of great significance for very low birth weight infants (VLBWI). The Yangtze River Delta is the most ecomonically developed area in China. However, there are few data on the care practices and survival of VLBWI in this region. OBJECTIVES: To investigate the prevalence, care practices and motality of VLBWI in Yangtze River Delta in China. METHODS: A multi-center retrospective investigation study was conducted at five tertiary hospitals within the Yangtze River Delta in China from January to December 2017. Clinical data included the general characteristics of the infants and the mothers, clinical prognosis, care practices in NICUs was collected by trained research members. RESULTS: During the study period, 1059 VLBWIs were included. Infants with birth weight < 750 g, 750-1000 g, 1000-1250 g and 1250-1500 g accounted for 2.3, 14.9, 34.8 and 47.8%, respectively. Premature rupture of membranes (17.8%) was the main cause of premature delivery. The catheterization rates of umbilical vein catheterization (UVC) and peripherally inserted central catheter (PICC) were 25.0 and 64.4%, respectively. The duration of parenteral nutrition was 27.0 ± 19.5 d, the meantime of feeding tube indwelling was 36.2 ± 24.2 d. The corrected gestational age of the infants who reached full oral feeding was 35.8 ± 2.7 weeks. The breast feeding rate in the investigated infants was 61.9%. The mortality rate of preterm infants was 3.4%. The incidence of main complications BPD, PDA, ROP, NEC and sepsis were 24.9, 29.9, 21.7, 9.4 and 13.3% respectively. CONCLUSIONS: Maternal and infant care practices need to be improved in the very preterm births. This study provides a baseline for the improvement in the further study.

Medical staff's sentiments on the establishment of quiet time in the NICU.

AIM: To explore the sentiments of medical staff in setting quiet time in a tertiary neonatal intensive care unit. BACKGROUND: Quiet time, which can help create a healing neonatal intensive care unit environment, is increasingly being valued by hospital administrators. METHODS: Semi-structured interviews were used to interview 12 neonatal intensive care unit staff members, with data analysed using the content analysis method. RESULTS: This study extracted four themes: support, concern, education and teamwork. CONCLUSIONS: If quiet time needs to be set up, implemented and maintained in the neonatal intensive care unit, it is necessary to establish a quiet time culture throughout the whole ward, to carry out detailed management of quiet time and to cooperate and communicate with multidisciplinary departments. IMPLICATIONS FOR NURSING MANAGEMENT: To keep the ward quiet and minimize handling during quiet time, it is necessary to take adequate steps from a management level. Targeted staff training and education allow staff to appreciate the necessity and urgency of setting quiet time for themselves and babies. It is also necessary to refine the educational content of noise reduction and minimal handling and provide clear guidance on the best means to carry out clinical work during quiet time. Nursing managers need to establish a monitoring system for NICU noise and manage various noise sources made from equipment and people.

[Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients].

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

Antibacterial Prenylated p-Hydroxybenzoic Acid Derivatives from Oberonia myosurus and Identification of Putative Prenyltransferases.

Twelve hitherto unknown tandem prenylated p-hydroxybenzoic acid derivatives, namely, oberoniamyosurusins A-L, together with five known derivatives, were isolated from an EtOH extract of the whole parts of the plant Oberonia myosurus. Compounds 10, 13, and 17 exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213 with MIC50 values ranging from 7.6 to 23 µg/mL. To determine the biosynthetic pathway of this class of tandem prenyl-substituted compounds, the full-length transcriptome of O. myosurus was sequenced, yielding 19.09 Gb of clean data and 10 949 nonredundant sequences. Two isoforms of p-hydroxybenzoic acid prenyltransferases were annotated and functionally characterized as the enzymes that might be involved in the biosynthesis of nervogenic acid (13) in Pichia pastoris.

Elucidation of the mechanism of action of pinitol against pressure overload-induced cardiac hypertrophy and fibrosis in an animal model of aortic stenosis.

The long-term imposition of pressure overload on the cardiac tissue causes left ventricular hypertrophy (LVH) and cardiac fibrosis. Pinitol has been reported to possess antioxidant potential. The aim was to evaluate the efficacy of pinitol against pressure overload-induced cardiac hypertrophy and fibrosis in the aortic stenosis (AS) rat model. Cardiac hypertrophy was produced in Sprague-Dawley rats by abdominal aortic constriction and treated with lisinopril (15 mg/kg) or pinitol (5, 10, and 20 mg/kg). Pressure overload-induced alterations in hemodynamic and left ventricular function tests, cardiac SOD, GSH, MDA, NO, Na-K-ATPase, and mitochondrial complex enzyme levels were significantly attenuated by pinitol. The upregulated mRNA expressions of cardiac ANP, BNP, cTn-I, TNF-α, IL-1ß, IL-6, Bax, Caspase-3, collagen-I, and cardiac apoptosis were markedly downregulated by pinitol. In conclusion, pinitol ameliorated pressure overload-induced LVH and fibrosis via its anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic potential in experimental AS.

Nonomuraea nitratireducens sp. nov., a new actinobacterium isolated from Suaeda australis Moq. rhizosphere.

A novel actinomycete, designated WYY166T, was isolated from the rhizosphere of Suaeda australis Moq. collected in Dongfang, PR China. The taxonomic position of this strain was investigated using a polyphasic approach. Phylogenetic analysis based on its 16S rRNA gene referred strain WYY166T to the genus Nonomuraea, and it was most closely related to the type strains Nonomuraea candida HMC10T, Nonomuraea turkmeniaca DSM 43926T, Nonomuraea maritima NBRC 106687T and Nonomuraea polychroma DSM 43925T (98.35, 97.60, 97.36 and 97.30% sequence similarity, respectively). Genome sequencing revealed a genome size of 11.27 Mbp and a G+C content of 71.10 mol%. The genome average nucleotide identity (ANI) values and the digital DNA - DNA hybridization (dDDH) values between strain WYY166T and the other species of the genus were found to be low (ANI 81.63~85.23 %, dDDH 23.6~31.6 %), suggesting that it represented a new species. The physiological evaluation showed that it had remarkable nitrate reduction activity. The whole-cell hydrolysates contained meso-diaminopimelic acid and madurose. The N-acyl type of muramic acid was acetyl. The major menaquinones were MK-9 (H4) (86.9 %) and MK-9 (H2) (13.1 %). The predominant fatty acids were iso-C16 : 0 (53.2 %), 10-methyl C17 : 0 (10.7 %), C17 : 1 ω6c (8.3 %) and iso-C16 : 1 h (7.3 %). These physiological, biochemical and chemotaxonomic data suggested that strain WYY166T should be classified as representing a novel species of the genus Nonomuraea, for which the name Nonomuraea nitratireducens sp. nov. is proposed. The type strain is WYY166T (=MCCC 1K03779T=KCTC 49343T).

Generation of tetramycin B derivative with improved pharmacological property based on pathway engineering.

Polyene antibiotics, including amphotericin, nystatin, pimaricin, and tetramycin, are important antifungal agents. Increasing the production of polyenes and generation of their improved analogues based on the biosynthetic pathway engineering has aroused wide concern in application researches. Herein, tetramycin and nystatin, both of which share most of acyl-CoA precursors, are produced by Streptomyces hygrospinosus var. beijingensis CGMCC 4.1123. Thus, the intracellular malonyl-CoA is found to be insufficient for PKSs (polyketide synthases) extension of tetramycin by quantitative analysis in this wild-type strain. To circumvent this problem and increase tetramycin titer, the acyl-CoA competing biosynthetic gene cluster (BGC) of nystatin was disrupted, and the biosynthetic genes of malonyl-CoA from S. coelicolor M145 were integrated and overexpressed in nys-disruption mutant strain (SY02). Moreover, in order to specifically accumulate tetramycin B from A, two copies of tetrK and a copy of tetrF were introduced, resulting in elevating tetramycin B fermentration titer by 122% to 865 ± 8 mg/L than the wild type. In this optimized strain, a new tetramycin derivative, 12-decarboxy-12-methyl tetramycin B, was generated with a titer of 371 ± 26 mg/L through inactivation of a P450 monooxygenase gene tetrG. Compared with tetramycin B, the new compound exhibited higher antifungal activity against Saccharomyces cerevisiae and Rhodotorula glutinis, but lower hemolytic toxicity to erythrocyte. This research provided a good example of employing biosynthetic engineering strategies for fermentation titer improvement of polyene and development of the derivatives for medicinal applications.

p-Aminophenylalanine Involved in the Biosynthesis of Antitumor Dnacin B1 for Quinone Moiety Formation.

Actinosynnema species produce diverse natural products with important biological activities, which represent an important resource of antibiotic discovery. Advances in genome sequencing and bioinformatics tools have accelerated the exploration of the biosynthetic gene clusters (BGCs) encoding natural products. Herein, the completed BGCs of dnacin B1 were first discovered in two Actinosynnema pretiosum subsp. auranticum strains DSM 44131T (hereafter abbreviated as strain DSM 44131T) and X47 by comparative genome mining strategy. The BGC for dnacin B1 contains 41 ORFs and spans a 66.9 kb DNA region in strain DSM 44131T. Its involvement in dnacin B1 biosynthesis was identified through the deletion of a 9.7 kb region. Based on the functional gene analysis, we proposed the biosynthetic pathway for dnacin B1. Moreover, p-amino-phenylalanine (PAPA) unit was found to be the dnacin B1 precursor for the quinone moiety formation, and this was confirmed by heterologous expression of dinV, dinE and dinF in Escherichia coli. Furthermore, nine potential PAPA aminotransferases (APAT) from the genome of strain DSM 44131T were explored and expressed. Biochemical evaluation of their amino group transformation ability was carried out with p-amino-phenylpyruvic acid (PAPP) or PAPA as the substrate for the final product formation. Two of those, APAT4 and APAT9, displayed intriguing aminotransferase ability for the formation of PAPA. The proposed dnacin B1 biosynthetic machinery and PAPA biosynthetic investigations not only enriched the knowledge of tetrahydroisoquinoline (THIQ) biosynthesis, but also provided PAPA building blocks to generate their structurally unique homologues.