Negative regulation of MurZ and MurA underlies the essentiality of GpsB- and StkP-mediated protein phosphorylation in Streptococcus pneumoniae D39.

GpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogen Streptococcus pneumoniae (pneumococcus; Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containing murZ (MurZ-family homolog of MurA) or murA that suppress ΔgpsB or ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overproduction of MurZ caused by ΔkhpAB mutations suppressed ΔgpsB or ΔstkP phenotypes to varying extents. ΔgpsB and ΔstkP were also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsB and ΔstkP were not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for StkP-mediated protein phosphorylation in exponentially growing D39 pneumococcal cells.

Extracorporeal Versus Conventional Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest: A Propensity Score Matching Cohort Study.

OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.

Effects of Three Kinds of Carbohydrate Pharmaceutical Excipients-Fructose, Lactose and Arabic Gum on Intestinal Absorption of Gastrodin through Glucose Transport Pathway in Rats.

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.

Uric acid levels and heart failure: A mendelian randomization study.

BACKGROUND AND AIMS: Uric acid, the end-product of purine metabolism within the human body, has been the subject of studies exploring its potential association with cardiovascular and cerebrovascular diseases. However, the precise relationship between uric acid levels and heart failure remains elusive. METHODS AND RESULTS: In this particular study, aggregated data from genome-wide association studies on uric acid and heart failure were utilized to perform a two-sample Mendelian randomization (MR) analysis utilizing R software. The aim was to uncover any causal link between these variables. The primary outcome was assessed using inverse variance weighted (IVW) methodology, while sensitivity analyses employed MR-Egger, weighted median (WME), and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) techniques. IVW results revealed a possible causal relationship between elevated uric acid levels and an increased risk of heart failure (OR: 1.09, 95 % CI: 1.01-1.17, P < 0.05). Encouragingly, the directions provided by MR-Egger and WME aligned with IVW findings, and no anomalies were detected in the remaining sensitivity analyses. CONCLUSION: These outcomes indicate the stability of the results of the study, thereby suggesting that heightened uric acid levels may contribute to an augmented risk of heart failure.

The Anti-Microbial Peptide Citrocin Controls Pseudomonas aeruginosa Biofilms by Breaking Down Extracellular Polysaccharide.

Citrocin is an anti-microbial peptide that holds great potential in animal feed. This study evaluates the anti-microbial and anti-biofilm properties of Citrocin and explores the mechanism of action of Citrocin on the biofilm of P. aeruginosa. The results showed that Citrocin had a significant inhibitory effect on the growth of P. aeruginosa with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 0.3 mg/mL. All five concentrations (1/4MIC, 1/2MIC, MIC, 2MIC, and 4MIC) of Citrocin inhibited P. aeruginosa biofilm formation. Citrocin at the MIC, 2MIC and 4MIC removed 42.7%, 76.0% and 83.2% of mature biofilms, respectively, and suppressed the swarming motility, biofilm metabolic activity and extracellular polysaccharide production of P. aeruginosa. Metabolomics analysis indicated that 0.3 mg/mL of Citrocin up- regulated 26 and down-regulated 83 metabolites, mainly comprising amino acids, fatty acids, organic acids and sugars. Glucose and amino acid metabolic pathways, including starch and sucrose metabolism as well as arginine and proline metabolism, were highly enriched by Citrocin. In summary, our research reveals the anti-biofilm mechanism of Citrocin at the metabolic level, which provides theoretical support for the development of novel anti-biofilm strategies for combatting P. aeruginosa.

Effects of Commonly used Surfactants, Poloxamer 188 and Tween 80, on the Drug Transport Capacity of Intestinal Glucose Transporters.

Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.

Structure and biological activities of glycoproteins and their metabolites in maintaining intestinal health.

Glycoproteins formed by covalent links between oligosaccharide and polypeptides are abundant in various food sources. They are less sensitivity to gastrointestinal enzymes, and hence many of them undergo fermentation in the colon by microorganisms. Therefore, the confer various health benefits on the intestinal ecosystem. However, the current understanding of the effect of glycoproteins on intestinal microorganisms and gut health is limited. This is probably due to their heterogeneous structures and complex metabolic programming patterns. The structure and biological activities of glycoproteins and their microbial metabolites were summarized in this review. The metabolic pathways activated by intestinal bacteria were then discussed in relation to their potential benefits on gut health. Food-derived glycoproteins and their metabolites improve gut health by regulating the intestinal bacteria and improving intestinal barrier function, thereby amplifying immune response. The data reviewed here show that food-derived glycoproteins are promising candidates for preventing various gastrointestinal diseases. Further studies should explore the interaction mechanisms between intestinal microorganisms and host metabolites.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1987857 .

Childhood trauma, peer victimization, and non-suicidal self-injury among Chinese adolescents: a latent variable mediation analysis.

BACKGROUND: Childhood and peer experiences can influence adolescents' perceptions of interpersonal relationships, which can, in turn, influence their emotional states and behavior patterns. Non-suicidal self-injury (NSSI) is now a common problem behavior among adolescents. The present study examined the role of childhood trauma and peer victimization in adolescents' NSSI. METHODS: A cross-sectional survey was conducted among 1783 adolescents (1464 girls and 318 boys) in the psychiatric outpatient clinics or wards of 14 psychiatric hospitals or general hospitals in nine provinces in China. Data were collected using the Multidimensional Peer Victimization Scale (MPVS), Short-form Childhood Trauma Questionnaire(CTQ-SF), and Functional Assessment of Self-Mutilation (FASM). Structural equation modeling (SEM) with latent variables was used to demonstrate the mediating role of peer victimization in the association between childhoodtrauma and NSSI. RESULTS: The SEM analysis demonstrated that peer victimization plays a partial mediating role in the relationship between childhood trauma and NSSI. In addition, several covariates (such as age, gender, education level, and place of residence) effectively regulated the relationship between peer victimization and NSSI. CONCLUSION: In future studies of NSSI among Chinese adolescents, attention should be paid to the roles of childhood trauma and peer bullying; there is a temporal sequence between these two variables and, to some extent, childhood trauma can have an impact on bullying during adolescence which, in turn, influences NSSI behavior.

Leaf Spot of Hedychium coronarium Caused by Colletotrichum gloeosporioides in China.

Hedychium coronarium (white ginger) is widely cultivated for garden decoration and folk medicine. Since 2020, symptomatic leaves showed brown necrosis and yellow borders on H. coronarium in the field (approximately 200 m2) at Southwest University, Rongchang District, Chongqing City. Small brown-yellow spots gradually enlarged and caused withering in severe cases with a mortality rate of around 10%. Disease incidence and severity varied from 55 to 65% and from 30 to 40%, respectively. Infected tissues (5 mm in diameter) were cut from lesion margins, surface sterilized in 70% ethanol for 10 s and 0.1% acidic mercuric chloride for 3 min, followed by rinsing in sterile water three times, and then were cultured onto potato dextrose agar (PDA) at 25 °C. Five isolates were transferred onto fresh PDA and purified by single-spore culturing. The colonies were initially white and turned hoary, and the diameter reached 32.95 to 38.37 mm × 32.42 to 38.61 mm after 3 days of incubation. Pale gray abundant fluffy aerial mycelia were arranged irregularly and densely. Hyphae were septate and branched, 2 to 5 µm in width. Conidiophores were pale brown, septate, branched, cylindrical to ampulliform. Conidia were hyaline, smooth-walled, cylindrical with obtuse ends, and 8.1 to 13.3 µm × 2.4 to 5.8 µm (n = 50) in size. Appressoria were medium brown to dark brown, aseptate, in irregular shape, solitary or in groups, and measured 1.5 to 12.5 µm × 2.1 to 13.3 µm. Morphological characteristics of isolates agreed with the description of Colletotrichum (Liu et al. 2015). Genomic DNA was extracted from fungal colonies incubated on PDA for 7 days following the instructions from the PlantGen DNA Kit (CWBIO, China). The internal transcribed spacer (ITS) region, and fragments of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), beta-tubulin (TUB2) and large subunit ribosomal DNA (LSU rDNA) genes were amplified by primer pairs ITS1/ ITS4, GDF1/GDR1, ACT512F/ACT783R (Naz et al. 2017), T1/Bt2b (Glass et al. 1995) and LROR/LR7 (Castlebury et al. 2002), respectively. The sequence of representative isolate CG-H (GenBank accession nos. OM010355, OM238213, OM238214, OM045778 and OM010358 for ITS, GAPDH, ACT, TUB2 and LSU rDNA, respectively) exhibited 99 to 100% identity to Colletotrichum gloeosporioides. A multi-locus phylogenetic tree with concatenated sequences of ITS, GAPDH, ACT and TUB regions was constructed using the maximum likelihood method by MEGA7, which revealed that strain CG-H was grouped with C. gloeosporioides. To confirm the pathogenicity, six healthy H. coronarium plants were surface sterilized, and conidial suspension (1 × 106 conidia/mL) was sprayed onto the leaves. Six plants were inoculated with sterile distilled water as controls. All the plants grew in a greenhouse at 25 °C under 12 h/12 h photoperiod. The experiment was repeated four times. Yellow lesions appeared after 7 days of inoculation, irregular-shaped brown spots were formed and slightly sunken within 14 days, and the whole leaf gradually became withered in 50 days. All inoculated plants exhibited leaf spot symptoms while the control plants remained asymptomatic. C. gloeosporioides was re-isolated from lesions of leaves and identified by morphology and sequence analysis, fully confirming Koch's postulates. This is the first report of C. gloeosporioides associated with H. coronarium leaf spot in China and worldwide. Further studies will be conducted on the sensitivity of C. gloeosporioides to various fungicides.

First Report of Leaf Blight of Hedychium coronarium Caused by Alternaria alternata in China.

Hedychium coronarium is an economically significant crop that is widely cultivated for its ornamental, aromatic, and medicinal value (Abbas et al. 2021). From 2020 to 2023, a leaf blight was observed in about 85% of H. coronarium growing in a production field (approximately 500 m2) at Southwest University, Chongqing, China (29° 150'-29° 41' N, 105° 17'-105° 44' E). Symptoms included dark brown necrotic tissue with a clear yellow border. When the disease became severe, affected leaves became dry and abscised. Symptomatic pieces (2 to 5 mm2) between necrotic and healthy tissues were collected from 20 leaf samples, then were immersed in 70% ethanol for 10 s, 0.1% mercury bichloride for 3 min, rinsed in sterile water three times, and placed onto potato dextrose agar (PDA). Four Alternaria isolates were obtained by transferring hyphal tips to new plates. All isolates had identical morphological traits. Cultures on PDA were initially white mycelium on the rim with a light brown center. At around the fourth day, the colony margin changed into light gray and the central part turned sooty black. Conidiophores were branched. Conidia were dark brown, ovoid or ellipsoid in shape, 3.4 to 13.2 µm × 4.1 to 23.5 µm (n = 50) with zero to four transverse and longitudinal septa. For molecular identification, DNA was extracted using the PlantGen DNA Kit CW0553A (Cwbio, Taizhou, China) for PCR amplification of internal transcribed spacer (ITS) region, and 28S large subunit ribosomal RNA (LSU), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Alternaria major allergen (Alt a 1) and actin (ACT) genes (Choi et al. 2022; Xie et al. 2022; Zhang et al. 2021). BLASTn searches showed that ITS, LSU, GAPDH, Alt a 1 and ACT of four isolates had 100% homology with the corresponding sequences of A. alternata strains MZ578214, KP940477, MK903028, MN655781 and MF564199, respectively. Representative sequences of one strain (AH1) with accession numbers of OK639009, OK639186, OK664976, OK664977 and OK664978 for ITS, LSU, GAPDH, Alt a 1 and ACT regions were deposited in GenBank. The maximum-likelihood tree generated by MEGA 5.10 demonstrated that the pathogenic isolate AH1 obtained from H. coronarium leaf was grouped in the same clade with A. alternata strain CBS121348, which was supported by 100% bootstrap values. To fulfill Koch's postulates, conidia were collected from a 7-day-old culture, suspended in sterile distilled water, and adjusted to 1 × 106 conidia/mL. Leaves on 6-month-old H. coronarium were surface disinfected with 1% sodium hypochlorite solution for 1 min, rinsed twice in water, and then inoculated with AH1 using a sprayer, while leaves treated with sterile water served as negative controls. The experiment was conducted four times, and each repeat contained 10 plants. Pathogenicity tests were performed in the greenhouse at 25°C with a 12 h photoperiod. Partial yellow lesions were observed 3 days of post-inoculation. As the disease progressed, the tawny color gradually spread across the leaf and the tip became dark brown within 7 days. The necrosis expanded and some small leaves were completely affected within 2 weeks. The pathogen was re-isolated from the lesions and re-identified through morphological traits and sequence analysis. A. alternata have been reported to cause leaf diseases in a variety of cereal crops, vegetables, and fruits across China (Sun et al. 2021; Zheng et al. 2015), which cause significant crop loss. To our knowledge, this is the first report of A. alternata causing leaf blight of H. coronarium in the world. More surveys are needed to explore the epidemiology and management strategies for disease caused by A. alternata in Southwest China.

Structure and in vitro digestion characteristics of skim goat milk protein during processing: effects of fat separation.

BACKGROUND: Although nonfat milk has been used worldwide in the industrial dairy process, little is known about the effects of fat separation during the manufacturing process on skim milk's structural and digestive properties. This study investigated the effects of the manufacturing process on the structure and in vitro digestion properties of skim goat milk, particularly emphasizing fat separation. RESULTS: Changes in the surface charge and hydrophobicity of milk proteins caused by fat separation resulted in oxidation and aggregation in the subsequent homogenization, heat and spray-drying processing, which affected its digestibility. Compared with separation by dish separator (DS), skim milk after tubular centrifugal separation (CS) showed a higher initial and final digestibility. The CS samples also had a lower surface hydrophobicity level and higher free sulfhydryl content, ζ-potential, and average particle size (P < 0.05). Goat milk protein after CS was more readily oxidized and aggregated during the subsequent homogenization and heat treatment, as evidenced by the higher carbonyl content and particle size. Centrifugal separation also converted more ß-sheets to α-helices, thus promoting the aggregation of oxidized skim milk protein. CONCLUSION: The skim milk after CS and DS demonstrated different structural and digestive properties. Skim goat milk products after CS were more susceptible to oxidant-induced protein structural changes, resulting in higher protein digestibility. These findings provide insights into the mechanism involved in the control of gastric digestion of skim milk during manufacturing process. © 2023 Society of Chemical Industry.

What drives the change of nitrogen and phosphorus loads in the Yellow River Basin during 2006-2017?

The Yellow River Basin (YRB) plays a very important role in China's economic and social development and ecological security. In particular, the ecosystem of the YRB is sensitive to climate change. However, the change of nutrient fluxes in this region during the past years and its main driving forces remain unclear. In this study, a hydrologic model R System for Spatially Referenced Regressions on Watershed Attributes (RSPARROW) was employed to simulate the spatio-temporal variations in the fluxes of total nitrogen (TN) and total phosphorus (TP) during the period of 2006-2017. The results suggested that the TN and TP loads increased by 138% and 38% during 2006-2014, respectively, and decreased by 66% and 71% from 2015 to 2017, respectively. During the period of 2006-2017, the annual mean fluxes of TN and TP in the YRB were in the range of 3.9 to 591.6 kg/km2/year and 1.7 to 12.0 kg/km2/year, respectively. TN flux was low in the upstream area of the Yellow River, and presented a high level in the middle and lower reaches. However, the flux of TP in Gansu and Ningxia section was slightly higher than that in the lower reaches of the Yellow River. Precipitation and point source are the key drivers for the inter-annual changes of TN loads in most regions of the YRB. While the inter-annual variations of TP loads in the whole basin are mainly driven by the point source. This study demonstrates the important impacts of climate change on nutrient loads in the YRB. Moreover, management measures should be taken to reduce pollution sources and thus provide solid basis for control of nitrogen and phosphorus in the YRB.

NBR1 mediates autophagic degradation of IRF3 to negatively regulate type I interferon production.

In the setting of virus infection, autophagy regulates the synthesis of type I interferon (IFN) via multiple mechanisms to prevent adverse overreaction. Interferon regulatory factor (IRF) 3, the dominant transcriptional factor of type I IFN, can be degraded via autophagy-lysosomal pathway. However, the exact regulatory mechanism is not yet well elucidated. IRF3 was targeted into autophagosome by interacting with cargo receptors including p62, NDP52 and NBR1. The recent studies have reported the mechanism of p62 and NDP52 sequestrating IRF3. This work aims to investigate the role of NBR1 in the process of IRF3 degradation. We found that blocking autophagy via ATG3/ATG7 knockout and chemical inhibitors both resulted in the accumulation of IRF3 protein and increased synthesis of type I IFN, while enhancing autophagy activity led to more obvious clearance of IRF3 in HEK293T cells infected with Sendai virus (SeV). Our data suggested that NBR1 bound both unphosphorylated and phosphorylated IRF3 through its ubiquitin-associated domain. Meanwhile, viral infection elevated the expression of NBR1, which sequentially formed a negative feedback loop to promote IRF3 degradation and hence optimized the type I IFN signaling. This study expands the knowledge of molecular mechanisms regulating the IRF3 stability and function during viral infection.

Genomic structure, expression and functional characterization of arginine kinase (EcAK) from Exopalaemon carinicauda.

Arginine kinase (AK, EC 2.7.3.3) plays an important role in cells with high, fluctuating energy requirements. In invertebrates, AK is the major phosphagen kinase that modulates the energy metabolism. Here, the full-length cDNA sequence encoding arginine kinase (EcAK) was obtained from the Exopalaemon carinicauda. The complete nucleotide sequence of EcAK contained a 1068 bp open reading frame (ORF) encoding EcAK precursor of 355 amino acids. The genomic DNA fragment of EcAK with the corresponding cDNA sequence is composed of 4 exons and 3 introns. The domain architecture of the deduced EcAK protein contained an ATP-gua_PtransN domain and an ATP-gua_Ptrans domain. EcAK mRNA was predominantly expressed in the muscle. The expression of EcAK in the prawns challenged with Vibrio parahaemolyticus and Aeromonas hydrophila changed in a time-dependent manner. Then, EcAK was recombinantly expressed in Pichia pastoris and the purified recombinant EcAK had the same enzymatic characterization as AK from the muscle of Euphausia superba. In conclusion, EcAK may play the same biological activity in E. carinicauda as those from other crustaceans.

A Study on the Evaluation of a Risk Score of Osteonecrosis of the Femoral Head Based on Survival Analysis.

BACKGROUND: This study aimed at developing a risk score predicting the probability of developing an osteonecrosis of the femoral head (ONFH) in patients with femoral neck fracture within 3 years after closed reduction internal fixation and evaluating its performance, clinical utility, and internal validity. METHODS: A retrospective follow-up study of 378 newly injured femoral neck fracture patients treated with 3 partially threaded parallel cannulated screws in 3 hospitals in Shanghai from March 2013 to January 2017 was performed. The patients were divided into development (n = 284) and validation (n = 94) cohorts. The risk score was constructed by Cox regression analysis in a form of nomogram. The performance and clinical utility were illustrated by box plots, calibration plots, and decision curve analysis. RESULTS: Eighty-three of 378 patients had developed ONFH within 3 years. Garden alignment index, time to surgery, preoperative displace, impaction, and postoperative malposition were used as predictors to construct the risk score in a form of nomogram. In the development and validation cohort, the concordance index was 0.96 and 0.94, respectively; the discrimination slope was 0.51 and 0.47, respectively. In both cohorts, the calibration slopes and intercepts were 1 and 0, respectively. The risk score was clinically useful between the risk threshold of 0% and 88%. The performance and utility in the validation data illustrated good repeatability. CONCLUSION: The risk score had satisfactory discrimination and calibration performance and demonstrated clinical utility with good internal validity. It managed to distinguish high-risk groups for post-traumatic ONFH.

Source emissions and climate change impacts on the multimedia transport and fate of persistent organic pollutants, Chaohu watershed, eastern China.

Emission intensity and climate change control the transport flux and fate of persistent organic pollutants (POPs) in multiple environmental compartments. This study applied a multimedia model (BETR model) to explore alternations in the spatio-temporal trends of concentrations and transport flux of benzopyrene (BaP), phenanthrene (Phe), perfluorooctane sulfonates (PFOS) and polychlorinated biphenyls (PCBs) in the Chaohu watershed, located in the lower reaches of the Yangtze River, China in response to changes in source emissions and climate. The potential historic and future risks of these pollutants also were assessed. The results suggest that current trends in concentrations and transport were similar to that of their emissions between 2005 and 2018. During the next 100 years, temporal trends and spatial patterns were not predicted to change significantly, which is consistent with climate change. Based on sensitivity and correlation analyses, climate change had significant effects on multi-media concentrations and transport fluxes of BaP, Phe, PFOS and PCBs, and rainfall intensity was the predominant controlling factor. Risk quotients (RQs) of BaP and Phe-in soil increased from 0.42 to 0.95 and 0.06 to 0.35, respectively, from 2005 to 2090, indicating potential risks. The RQs of the other examined contaminants exhibited little potential risk in soil, water, or sediment. Based on spatial patterns, it was inferred that the ecosystem around Lake Chaohu is the most at risk. The study provides insights needed for local pollution control of POPs in the Chaohu watershed. In addition, the developed approach can be applied to other watersheds world-wide.

S1 Domain RNA-Binding Protein CvfD Is a New Posttranscriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39.

Posttranscriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. However, the pneumococcal genome contains genes for other RNA-binding proteins, including at least six S1 domain proteins: ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins with unknown functions. Here, we characterize the function of one of these conserved, yet uncharacterized, S1 domain proteins, SPD_1366, which we have renamed CvfD (conserved virulence factor D), since loss of the protein results in attenuation of virulence in a murine pneumonia model. We report that deletion of cvfD impacts the expression of 144 transcripts, including the pst1 operon, encoding phosphate transport system 1 in S. pneumoniae We further show that CvfD posttranscriptionally regulates the PhoU2 master regulator of the pneumococcal dual-phosphate transport system by binding phoU2 mRNA and impacting PhoU2 translation. CvfD not only controls expression of phosphate transporter genes but also functions as a pleiotropic regulator that impacts cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data show that CvfD exerts a broad impact on pneumococcal physiology and virulence, partly by posttranscriptional gene regulation.IMPORTANCE Recent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen S. pneumoniae However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1 domain RNA-binding protein CvfD, a homolog of general stress protein 13 identified, but not extensively characterized, in other Firmicutes species. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.

Rethinking the impact of RG-I mainly from fruits and vegetables on dietary health.

Rhamnogalacturonan I (RG-I) pectin is composed of backbone of repeating disaccharide units →2)-α-L-Rhap-(1→4)-α-D-GalpA-(1→ and neutral sugar side-chains mainly consisting of arabinose and galactose having variable types of linkages. However, since traditional pectin extraction methods damages the RG-I structure, the characteristics and health effects of RG-I remains unclear. Recently, many studies have focused on RG-I, which is often more active than the homogalacturonan (HG) portion of pectic polysaccharides. In food products, RG-I is common to fruits and vegetables and possesses many health benefits. This timely and comprehensive review describes the many different facets of RG-I, including its dietary sources, history, metabolism and potential functionalities, all of which have been compiled to establish a platform for taking full advantage of the functional value of RG-I pectin.

Evaluation and comparison of six GRACE models for the stratification of undifferentiated chest pain in the emergency department.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is recommended for stratifying chest pain. However, there are six formulas used to calculate the GRACE score for different outcomes of acute coronary syndrome (ACS), including death (Dth) or composite of death and myocardial infarction (MI), while in hospital (IH), within 6 months after discharge (OH6m) or from admission to 6 months later (IH6m). We aimed to perform the first comprehensive evaluation and comparison of six GRACE models to predict 30-day major adverse cardiac events (MACEs) in patients with acute chest pain in the emergency department (ED). METHODS: Patients with acute chest pain were consecutively recruited from August 24, 2015 to September 30, 2017 from the EDs of two public hospitals in China. The 30-day MACEs included death, acute myocardial infarction (AMI), emergency revascularization, cardiac arrest and cardiogenic shock. The correlation, calibration, discrimination, reclassification and diagnostic accuracy at certain cutoff values of six GRACE models were evaluated. Comparisons with the History, ECG, Age, Risk Factors, and Troponin (HEART) and Thrombolysis in Myocardial Infarction (TIMI) scores were conducted. RESULTS: A total of 2886 patients were analyzed, with 590 (20.4%) patients experiencing outcomes. The GRACE (IHDthMI), GRACE (IH6mDthMI), GRACE (IHDth), GRACE (IH6mDth), GRACE (OH6mDth) and GRACE (OH6mDthMI) showed positive linear correlations with the actual MACE rates (r ≥ 0.568, P < 0.001). All these models had good calibration (Hosmer-Lemeshow test, P ≥ 0.073) except GRACE (IHDthMI) (P < 0.001). The corresponding C-statistics were 0.83(0.81,0.84), 0.82(0.81,0.83), 0.75(0.73,0.76), 0.73(0.72,0.75), 0.72(0.70,0.73) and 0.70(0.68,0.71), respectively, first two of which were comparable to HEART (0.82, 0.80-0.83) and superior to TIMI (0.71, 0.69-0.73). With a sensitivity ≥95%, GRACE (IHDthMI) ≤81 and GRACE (IH6mDthMI) ≤79 identified 868(30%) and 821(28%) patients as low risk, respectively, which were significantly better than other GRACEs and HEART ≤3(22%). With a specificity ≥95%, GRACE (IHDthMI) > 186 and GRACE (IH6mDthMI) > 161 could recognize 12% and 11% patients as high risk, which were greater than other GRACEs, HEART ≥8(9%) and TIMI ≥5(8%). CONCLUSIONS: In this Chinese setting, certain strengths of GRACE models beyond HEART and TIMI scores were still noteworthy for stratifying chest pain patients. The validation and reasonable application of appropriate GRACE models in the evaluation of undifferentiated chest pain should be recommended.

Physicochemical and Digestion Properties of Potato Starch Were Modified by Complexing with Grape Seed Proanthocyanidins.

Dietary intake of potato starch could induce a dramatic increase in blood glucose and is positively associated with chronic metabolic diseases (type II diabetes, cardiovascular disease, etc.). Grape seed proanthocyanidins (GSP) are known to decrease starch digestion by inhibiting digestive enzymes or changing the physicochemical properties of starch. In the present study, GSP were complexed with potato starch to prepare polyphenol-starch complexes. The physiochemical properties and digestibility of complexes were investigated by in vitro digestion model, X-ray diffraction, differential scanning calorimetry, rapid visco analyzer, Fourier transform infrared spectroscopy as well as texture profile analysis. Results indicated that the peak viscosity, breakdown, trough, and setback of the complexes disappeared, replaced by a special continuous increase in paste viscosity. The complexes showed a lower final viscosity and higher thermal stability with the increasing binding amount of GSP. GSP decreased the hardness of the complexes' gel significantly. FT-IR indicated that GSP might interact with potato starch through noncovalent forces. Additionally, the complexes also showed a higher content of slowly digestible starch and resistant starch than that of the native starch. Thus, we inferred that the addition of GSP could modify the digestibility of potato starch and be an optional way to modify the starch with lower digestion.