"Primer shot" fractionation with an early treatment break is theoretically superior to consecutive weekday fractionation schemes for early-stage non-small cell lung cancer.

PURPOSE: Radiotherapy is traditionally given in equally spaced weekday fractions. We hypothesize that heterogeneous interfraction intervals can increase radiosensitivity via reoxygenation. Through modeling, we investigate whether this minimizes local failures and toxicity for early-stage non-small cell lung cancer (NSCLC). METHODS: Previously, a tumor dose-response model based on resource competition and cell-cycle-dependent radiosensitivity accurately predicted local failure rates for early-stage NSCLC cohorts. Here, the model mathematically determined non-uniform inter-fraction intervals minimizing local failures at similar normal tissue toxicity risk, i.e., iso-BED3 (iso-NTCP) for fractionation schemes 18Gyx3, 12Gyx4, 10Gyx5, 7.5Gyx8, 5Gyx12, 4Gyx15. Next, we used these optimized schedules to reduce toxicity risk (BED3) while maintaining stable local failures (TCP). RESULTS: Optimal schedules consistently favored a "primer shot" fraction followed by a 2-week break, allowing tumor reoxygenation. Increasing or decreasing the assumed baseline hypoxia extended or shortened this optimal break by up to one week. Fraction sizes of 7.5 Gy and up required a single primer shot, while smaller fractions needed one or two extra fractions for full reoxygenation. The optimized schedules, versus consecutive weekday fractionation, predicted absolute LF reductions of 4.6%-7.4%, except for the already optimal LF rate seen for 18Gyx3. Primer shot schedules could also reduce BED3 at iso-TCP with the biggest improvements for the shortest schedules (94.6Gy reduction for 18Gyx3). CONCLUSION: A validated simulation model clearly supports non-standard "primer shot" fractionation, reducing the impact of hypoxia-induced radioresistance. A limitation of this study is that primer-shot fractionation is outside prior clinical experience and therefore will require clinical studies for definitive testing.

Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle.

Itaconic acid (IA), a metabolite generated by the tricarboxylic acid (TCA) cycle in eukaryotic immune cells, and its derivative dimethyl itaconate (DI) exert antibacterial functions in intracellular environments. Previous studies suggested that IA and DI only inhibit bacterial growth in carbon-limited environments; however, whether IA and DI maintain antibacterial activity in carbon-enriched environments remains unknown. Here, IA and DI inhibited the bacteria with minimum inhibitory concentrations of 24.02 mM and 39.52 mM, respectively, in a carbon-enriched environment. The reduced bacterial pathogenicity was reflected in cell membrane integrity, motility, biofilm formation, AI-2/luxS, and virulence. Mechanistically, succinate dehydrogenase (SDH) activity and fumaric acid levels decreased in the IA and DI treatments, while isocitrate lyase (ICL) activity was upregulated. Inhibited TCA circulation was also observed through untargeted metabolomics. In addition, energy-related aspartate metabolism and lysine degradation were suppressed. In summary, these results indicated that IA and DI reduced bacterial pathogenicity while exerting antibacterial functions by inhibiting TCA circulation. This study enriches knowledge on the inhibition of bacteria by IA and DI in a carbon-mixed environment, suggesting an alternative method for treating bacterial infections by immune metabolites.

Probiotic characterization and comparison of broiler-derived lactobacillus strains based on technique for order preference by similarity to ideal solution analysis.

A total of 10 lactobacillus strains were isolated from broiler chickens and their probiotic properties including tolerance to gastrointestinal fluids and heat treatment, antimicrobial activity, adhesion capacity to intestinal cells, surface hydrophobicity, autoaggregation, antioxidative activity, and immunomodulatory effects on chicken macrophages were evaluated. The Limosilactobacillus reuteri (LR) was the most frequently isolated species, followed by Lactobacillus johnsonii (LJ) and Ligilactobacillus salivarius (LS). All isolates showed good resistance to simulated gastrointestinal conditions and antimicrobial activity against 4 indicator strains including Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, and Proteus mirabilis LR 21 exhibited excellent performances on autoaggregation, hydrophobicity and adhesion capacity to Caco-2 intestinal cells. In the meantime, this strain also possessed considerable tolerance to heat treatment, which indicated great potential to be used in the feed industry. However, LJ 20 strain had the highest free radical scavenging activity compared with the other strains. Furthermore, qRT-PCR results revealed that all isolated strains significantly increased the transcriptional levels of proinflammatory genes and tended to induce the M1-type polarization on HD11 macrophages. Particularly, the technique for order preference by similarity to ideal solution (TOPSIS) was adopted in our study to compare and select the most promising probiotic candidate based on in vitro evaluation tests.

Neuronal activities in the rostral ventromedial medulla associated with experimental occlusal interference-induced orofacial hyperalgesia.

The imbalanced conditions of pronociceptive ON-cells and antinociceptive OFF-cells in the rostral ventromedial medulla (RVM) alter nociceptive transmission and play an important role in the development of chronic pain. This study aimed to explore the neuroplastic mechanisms of the RVM ON-cells and OFF-cells in a male rat model of experimental occlusal interference (EOI)-induced nociceptive behavior reflecting orofacial hyperalgesia and in modified models involving EOI removal at early and later stages. We recorded the mechanical head withdrawal thresholds (HWTs), orofacial operant behaviors, and the activity of identified RVM ON-cells and OFF-cells in these rats. EOI-induced orofacial hyperalgesia could be relieved by EOI removal around postoperative day 3; this effect could be inhibited by intra-RVM microinjection of the kappa-opioid receptor agonist U-69593. EOI removal around postoperative day 8 did not relieve the orofacial hyperalgesia which could however be reversed by intra-RVM microinjection of the NK-1 receptor antagonist L-733060. The activity of ON-cells and OFF-cells did not change during both the initial 3 and 6 days of EOI. When EOI was removed on postoperative day 3, OFF-cell responses decreased, contributing to the reversal of hyperalgesia. When EOI lasted for 8 days or was removed on postoperative day 8, spontaneous activity and stimulus-evoked responses of ON-cell increased, contributing to the maintained hyperalgesia. In contrast, when the EOI lasted for 14 days, OFF-cell responses decreased, possibly participating in the maintenance of hyperalgesia with persistent EOI. Our results reveal that adaptive changes in the RVM were associated with orofacial pain following EOI placement and removal.SIGNIFICANCE STATEMENTA considerable proportion of patients suffered from chronic orofacial pain throughout life despite the therapies given or removal of potential etiological factors. However, current therapies lack effectiveness due to limited knowledge of the chronicity mechanisms. Using electrophysiological recording, combined with a behavioral test, we found that the prevailing descending facilitation in the rostral ventromedial medulla (RVM) participates in the maintenance of orofacial hyperalgesia following late removal of nociceptive stimuli, while the prevailing descending inhibition from the RVM may contribute to the reversal of orofacial hyperalgesia following early removal of nociceptive stimuli. Thus, variable clinical outcomes of orofacial pain may be associated with descending modulation and an optimal window of time may exist in the management of chronic orofacial pain.

[Effects of intermittent hypoxia intestinal bacterial translocation on mesenteric lymph node injury].

Objective: To observe the effect of intermittent hypoxia on intestinal bacterial translocation and mesenteric lymph node (MLN) structure and explore its mechanism. Methods: Twenty-four adult male Wistar rats were randomly divided into an experimental group (HI group) and a control group (UC group), with 12 rats in each. During the experiment, both groups were fed under the same conditions, but the HI group received simulated sleep apnea with hypoxic treatment. On the last day of the 2nd and 4th week of the experiment, 20% urethane(0.7 ml/100g) was used for anesthesia, and MLNs and corresponding small intestinal tissues were aseptically collected.HE staining was used to observe the microscopic changes of the tissues. The lymph node tissue was sent for pathogenic culture. The levels of oxide dismutase (SOD), lipid peroxide (MDA) and reactive oxygen species (ROS) were measured for the extent of oxidative stress. Serum diamine oxidase (DAO) was measured to assess the extent of intestinal mucosal damage. Result: MLNs and their corresponding small intestines were damaged in the HI group as compared to the UC group. With the prolongation of intermittent hypoxic time, the number of germinal centers in MLNs was significantly reduced, with the volume reduced, cortical medullary fusion aggravated, and the area ratio increased. The intestinal tissue showed severe damage to the intestinal epithelium, increased permeability, mucosal edema, and changes of the crypts. At the 4th week, MLNs in the HI group grew Clostridium perfringens under anaerobic conditions, confirming intestinal bacterial translocation. The contents of ROS, SOD and MDA in MLNs of the HI group were significantly higher than those in the UC group (P<0.05). At the 2nd week and the 4th week, the contents of ROS, SOD and MDA were not significantly changed in the UC group(P>0.05). While the content of ROS and MDA in MLNs of the HI group at 4th week was significantly higher than that in the second week (P<0.05), but no change of SOD was observed (P>0.05). Serum DAO levels in the HI group were higher than those in the UC group at week 2 and week 4 (P<0.05), suggesting that the degree of intestinal mucosal injury in the HI group was more serious than that in the UC group. Conclusion: Hypoxic exposure aggravated the degree of oxidative stress in rats. With the prolongation of intermittent hypoxia, the intestinal mucosa of rats was seriously damaged. The intestinal flora shifted to damage the structure of mesenteric lymph nodes, and oxidative stress was further aggravated, which in turn affected the integrity of the intestinal autoimmune function.

Contrast-enhanced Ultrasound (CEUS) vs contrast-enhanced computed tomography for multilocular cystic renal neoplasm of low malignant potential: A retrospective analysis for diagnostic performance study.

Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) might be benefited from nephron-sparing surgery. Contrast-enhanced computed tomography is used for the diagnosis of MCRNLMP but contrast-enhanced ultrasound has lack of nephrotoxicity and several advantages over contrast-enhanced computed tomography and contrast-enhanced magnetic resonance. The purpose of the study was to compare diagnostic parameters of preoperative contrast-enhanced ultrasound against contrast-enhanced computed tomography for the detection of MCRNLMP in patients who faced curative surgery for complex cystic renal mass.Data regarding contrast-enhanced ultrasound, contrast-enhanced computed tomography, and clinicopathological results of 219 patients who underwent curative surgery for complex cystic renal mass (Bosniak classification III or IV) were retrospectively collected and analyzed. Bosniak classification for imaging modality and the 2016 WHO criteria for clinic pathology were used for detection of MCRNLMP.Contrast-enhanced ultrasound, contrast-enhanced computed tomography, and clinicopathology were detected 68, 66, and 67 as a MCRNLMP respectively. Contrast-enhanced ultrasound and contrast-enhanced computed tomography had 30.37% and 29.27% sensitivities for the detection of MCRNLMP. While 60% and 50% specificities respectively. Bosniak classification III (P = .045) and lower mean Hounsfield unit (P = .049) were associated with the prevalence of MCRNLMP. Contrast-enhanced computed tomography was detected 6 and 7, while contrast-enhanced ultrasound detected 3 and 2 complex cystic renal mass as false positive and false negative MCRNLMP respectively. A contrast-enhanced ultrasound had 0.011 to 1.0 diagnostic confidence and contrast-enhanced computed tomography had 0.045 to 0.983 diagnostic confidence for decision making of nephron-sparing surgeries.Contrast-enhanced ultrasound may have better visualization of MCRNLMP than contrast-enhanced computed tomography.Level of Evidence: III.

Proliferation and migration of hepatocellular carcinoma are accelerated by LINC01287 via the miR-559/TCF12 axis.

OBJECTIVE: To uncover the role of LINC01287 in the progression of hepatocellular carcinoma (HCC) and the indicated molecular mechanism. PATIENTS AND METHODS: Relative levels of LINC01287 and miR-559 in 32 pairs of HCC tissues and normal ones, as well as HCC cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were depicted for assessing the diagnostic and prognostic potentials of LINC01287 in HCC, respectively. Proliferative and migratory capacities in HCC cells influenced by LINC01287 were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. The regulatory loop LINC01287/miR-559/TCF12 was ascertained by Dual-Luciferase reporter assay. The involvement of the regulatory loop in the progression of HCC was examined via rescue experiments. RESULTS: LINC01287 was upregulated in HCC tissues and cell lines, whereas miR-559 was downregulated. LINC01287 displayed certain diagnostic and prognostic potentials in HCC. Knockdown of LINC01287 could inhibit proliferative and migratory capacities in HCC cells. The regulatory loop LINC01287/miR-559/TCF12 was responsible for the aggravation of HCC. CONCLUSIONS: LINC01287 drives proliferative and migratory capacities in HCC via targeting the miR-559/TCF12 axis.

Association between anemia and cognitive decline among Chinese middle-aged and elderly: evidence from the China health and retirement longitudinal study.

BACKGROUND: Our objective was to characterize the relationship of anemia and hemoglobin concentrations with cross-sectional cognitive functions and changes in cognitive functions over 2 years in a large sample of Chinese middle aged and elderly. METHODS: Ten thousand nine hundred eighteen adults aged 45 years or older participating in the China Health and Retirement Longitudinal Study (CHARLS) were used for cross-sectional analyses and 9324 were used for longitudinal analysis. Cognitive functions were assessed by memory recall (episodic memory), mental status (TICS), and global cognitive function at baseline survey (Visit 1) and first follow-up survey (Visit 2). The lower the cognitive test score, the worse the cognitive function. Anemia was defined as hemoglobin concentrations lower than 13 g/dl for men and lower than 12 g/dl for women. Adjusted multivariate regression analyses were used to explore the relationships of different cognitive domains with anemia and hemoglobin concentration. RESULTS: Overall, the prevalence of anemia was 12.86% and the mean hemoglobin concentration was 14.37 ± 2.20 g/dl. After adjusting for socio-demographic and health-related covariates, the cross-sectional association between anemia and global cognitive function [ß (95%CI) = - 0.49(- 0.69~ - 0.29)], episodic memory [ß (95%CI) = - 0.14(- 0.23~ - 0.05)], and TICS [ß (95%CI) = - 0.23(- 0.38~ - 0.08)] were significant and did not differ by gender. The hemoglobin concentration was also associated with global cognitive function among the whole sample (P < 0.05 for all). The longitudinal analyses showed global cognitive function and episodic memory were associated with anemia independent of covariates (P < 0.05 for all). Sensitivity analyses further provided significant results showing the association between anemia and cognition decline (P < 0.05). CONCLUSION: There was a cross-sectional and longitudinal association between anemia and accelerated decline in cognitive functions in Chinese middle-aged and elderly. This suggests that anemia and low hemoglobin concentrations are independent risk factors of cognitive decline.

[Effects of rhodiola rosea on oxidative stress and negative emotional states in patients with obstructive sleep apnea].

Objective:The aim of this study is to investigate the effects of rhodiola rosea on oxidative stress, anxiety and depression in patients with OSA. Method:Ninety patients with moderate and severe OSA patients with negative emotions diagnosed by PSG, self-rating depression scale （SDS） and self-rating anxiety scale （SAS） were selected from the respiratory department of our hospital from February 2015 to February 2018. According to the random number table method, the patients were randomly divided into non-invasive ventilator group, rhodiola rosea+non-invasive ventilator group and rhodiola rosea group, with 30 cases in each group. Patients in the non-invasive ventilator group were treated with continuous positive airway pressure （CPAP） for 3 months, and those in the rhodiola rosea+non-invasive ventilator group were treated with oral rhodiola capsules for 3 months on the basis of CPAP, and those in the rhodiola rosea treatment group were treated with pure oral rhodiola capsules for 3 months. The changes of SDS and SAS before and after the three groups were compared, and the changes of serum SOD and MDA were detected by immunoenzyme-linked adsorption for comparative analysis. Result:There were no significant differences in SDS and SAS scores between the three groups （P>0.05）. SDS and SAS scores of patients in the rhodiola rosea+non-invasive ventilator group decreased after treatment （P<0.05） compared with those in the non-invasive ventilator group. SDS and SAS scores of patients in the rhodiola treatment group increased after treatment （P<0.05）. Compared with those in the rhodiola treatment group, SDS and SAS scores of patients in the rhodiola+non-invasive breathing group decreased after treatment （P<0.05）. Three group patients were no significant difference in serum SOD and malondialdehyde （MDA） before treatment （P>0.05）. Compared with before treatment, serum SOD level were all increased and MDA level were all decreased in the three groups after treatment （P<0.05）. Compared with noninvasive breathing unit after treatment, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased （P<0.05）, and for the treatment group after treatment in patients with serum SOD levels drop, the MDA levels （P<0.05）, and the after rhodiola rosea treatment group compared, rhodiola+noninvasive breathing unit after treatment in patients with elevated levels of serum SOD, MDA level decreased （P<0.05）. Conclusion:Rhodiola may improve the negative emotions such as anxiety and depression by inhibiting oxygen free radicals and lipid peroxidation in patients with OSA.

Effects of AIF-1 inflammatory factors on the regulation of proliferation of breast cancer cells.

The purpose of this study was to explore the effect of Allograft Inflammatory Factor 1 (AIF-1) on the regulation of proliferation of breast cancer cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), cell culture and counting, and mass spectrometry were performed. The biologically active high-purity recombinant protein rhAIF-1 was obtained by optimizing the rhAIF-1 protein purification system, and MDA-MB-231 and MDA-MB-361 breast cancer cell lines were used. After adding to the culture medium, rhAIF-1 was found to promote cell proliferation in dose-dependent and time-dependent manners. The purified protein rhAIF-1 was marked with rhodamine and incubated with the cells. Confocal imaging analysis revealed that the foreign protein was localized in the cytoplasm, and rhAIF-1 was unevenly distributed in the cytoplasm. Although AIF-1 accumulates around the nucleus, it can not enter the nucleus, suggesting that other factors might be involved in the regulation of cell proliferation. In order to find the possible interacting protein of rhAIF-1, protein immunoprecipitation technique and mass spectrometry were employed, and it was indicated that ADAM28m was the possible interacting protein of rhAIF-1. The interaction between rhAIF-1 and ADAM28m was validated by immunoprecipitation along with Western blotting. It was found that rhAIF-1 could precipitate ADAM28m protein by immunoprecipitation. The results indicated that IF-1 participates in the development of breast cancer by interacting with ADAM28m and activating downstream signaling pathways. It was concluded that AIF-1 provides a new idea for the molecular mechanism of breast cancer cell proliferation and acts as a new target for the prevention and treatment of breast cancer in the future.

[Effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apnea complicated with metabolic syndrome].

Objective:The aim of this study is to analyze the effects of glutathione on oxidative stress, leptin and adiponectin in patients with obstructive sleep apnea（OSA） complicated with metabolic syndrome. Method:One hundred and fifty-nine patients with OSA and MS were enrolled in the group A according to the exclusion criteria. One hundred and fifty-nine patients with MS group were not included in the OSA group, and 159 patients were included in the control group. Before and after treatment, the levels of serum malondialdehyde （MDA）, superoxide dismutase （SOD）, Leptin and ADP were respectively detected, and the clinical effects of the three groups were compared. Result:Compared with the control group, the contents of MDA and Leptin in the case A and B groups were significantly higher than that of the control group, and the contents of SOD and ADP were significantly lower than that of the control group, and the difference was statistically significant, especially in case group A. The level of SOD and ADP was significantly higher in the group after treatment than before treatment, and the level of MDA and Leptin was significantly lower than before treatment. The difference was statistically significant, especially in case group A, too. Conclusion:Patients with OSA and MS are associated with oxidative stress. Glutathione can effectively improve the body's ability to resist oxidative stress, reduce oxidative damage, reduce leptin, and increase ADP levels.

[Progress in studies on obstructive sleep apnea and intestinal microecological balance].

SummaryObstructive sleep apnea （OSA） is closely related to the development of various diseases. Hypoxic perfusion caused by OSA can mediate the occurrence of inflammatory reactions or aggravate metabolic disorders to affect intestinal microecological balance. Intestinal bacteria can participate in the development of inflammatory reaction or metabolic disorder by itself or its components, and the oxidative stress reaction of the body develops in a vicious circle. The mechanism has not yet been fully elucidated, so we reviewed the research progress on OSA and intestinal microecological balance.

Spatiotemporally Skewed Activation of Programmed Cell Death Receptor 1-Positive T Cells after Epstein-Barr Virus Infection and Tumor Development in Long-Term Fully Humanized Mice.

Humanized mice developing functional human T cells endogenously and capable of recognizing cognate human leukocyte antigen-matched tumors are emerging as relevant models for studying human immuno-oncology in vivo. Herein, mice transplanted with human CD34+ stem cells and bearing endogenously developed human T cells for >15 weeks were infected with an oncogenic recombinant Epstein-Barr virus (EBV), encoding enhanced firefly luciferase and green fluorescent protein. EBV-firefly luciferase was detectable 1 week after infection by noninvasive optical imaging in the spleen, from where it spread rapidly and systemically. EBV infection resulted into a pronounced immunologic skewing regarding the expansion of CD8+ T cells in the blood outnumbering the CD4+ T and CD19+ B cells. Furthermore, within 10 weeks of infections, mice developing EBV-induced tumors had significantly higher absolute numbers of CD8+ T cells in lymphatic tissues than mice controlling tumor development. Tumor outgrowth was paralleled by an up-regulation of the programmed cell death receptor 1 on CD8+ and CD4+ T cells, indicative for T-cell dysfunction. Histopathological examinations and in situ hybridizations for EBV in tumors, spleen, liver, and kidney revealed foci of EBV-infected cells in perivascular regions in close association with programmed cell death receptor 1-positive infiltrating lymphocytes. The strong spatiotemporal correlation between tumor development and the T-cell dysfunctional status seen in this viral oncogenesis humanized model replicates observations obtained in the clinical setting.

Expression and purification of antimicrobial peptide AP2 using SUMO fusion partner technology in Escherichia coli.

Apidaecins (APs) are proline-rich antimicrobial peptides that were isolated from Apismelifera. APs possess broad-spectrum activities against Gram-negative bacteria and exhibit immune-modulatory functions. AP2, an artificial mutant AP peptide with improved activities, was expressed in Escherichia coli expression system using small ubiquitin-related modifier (SUMO) fusion technology and ZYM-5052 auto-induction medium. Approximately 23 mg of recombinant fusion protein smt3AP2 was purified per litre cultivated medium. After SUMO protease (Ulp) cleavage of smt3AP2, recombinant AP2 was further purified by affinity and cation exchange chromatography. The pure recombinant AP2 with calculated value of 2·23 kDa reached a yield of 2·7 mg l-1 and exhibited powerful antibacterial activity towards E. coli K88 with minimum inhibitory concentration at 5 µg ml-1 . The recombinant fusion strategy presented in this study allows convenient high yield and easy purification of recombinant AP2. SIGNIFICANCE AND IMPACT OF THE STUDY: AP2, an artificial mutant apidaecin (AP) peptide based on APs, has improved activities and may be regarded as a promising antibiotic alternatives. The secreted expression of antimicrobial peptide is of the greatest challenges because the antibacterial activity is not beneficial to the host. Our data suggest that the recombinant fusion strategy allows convenient high yield and easy purification of recombinant AP2.

[Correlation study between the levels of serum MCP-1,SAA and cognitive function in patients with COPD-OSAHS].

Objective:To study the correlation among the serum monocyte chemoattractant protein-1 (MCP-1),serum amyloid A(SAA) and the level of cognitive function in patients with chronic obstructive pulmonary disease and obstructive sleep apnea hypopnea syndrome overlap syndrome(OS).Method:Sixty patients with OS were in the experimental group, and 33 patients with COPD were in control group. The serum levels of MCP-1 and SAA were measured, and the correlation among MCP-1, SAA and cognitive function was observed by the Montreal scale.Result:①The serum levels of MCP-1 and SAA in OS group were (159.85±21.38)ng/L and (122.64±42.49)ng/L respectively,which in control group were (135.02±15.31)ng/L and (71.37±10.16)ng/L respectively.There were the was statistically significant difference between the two groups(P<0.05). ②Montreal scale score and its sub items in OS group were lower than the control group.The difference was statistically significant (P<0.05).③There was significant negative correlation between Montreal scale and the serum levels of MCP-1(r=-0.654,P<0.05) and SAA (r=-0.617,P<0.05) in OS group.Conclusion:Patients in the OS group had obvious cognitive impairment compared with the ones in control group, which suggested that OSAHS might be an independent risk factor for cognitive impairment. The cognitive function of OS patients was negatively related to MCP-1 and SAA, which suggested that MCP-1 and SAA played a role in the occurrence of cognitive impairment in OS patients.

The Plastid Terminal Oxidase is a Key Factor Balancing the Redox State of Thylakoid Membrane.

Mitochondria possess oxygen-consuming respiratory electron transfer chains (RETCs), and the oxygen-evolving photosynthetic electron transfer chain (PETC) resides in chloroplasts. Evolutionarily mitochondria and chloroplasts are derived from ancient α-proteobacteria and cyanobacteria, respectively. However, cyanobacteria harbor both RETC and PETC on their thylakoid membranes. It is proposed that chloroplasts could possess a RETC on the thylakoid membrane, in addition to PETC. Identification of a plastid terminal oxidase (PTOX) in the chloroplast from the Arabidopsis variegation mutant immutans (im) demonstrated the presence of a RETC in chloroplasts, and the PTOX is the committed oxidase. PTOX is distantly related to the mitochondrial alternative oxidase (AOX), which is responsible for the CN-insensitive alternative RETC. Similar to AOX, an ubiquinol (UQH2) oxidase, PTOX is a plastoquinol (PQH2) oxidase on the chloroplast thylakoid membrane. Lack of PTOX, Arabidopsis im showed a light-dependent variegation phenotype; and mutant plants will not survive the mediocre light intensity during its early development stage. PTOX is very important for carotenoid biosynthesis, since the phytoene desaturation, a key step in the carotenoid biosynthesis, is blocked in the white sectors of Arabidopsis im mutant. PTOX is found to be a stress-related protein in numerous research instances. It is generally believed that PTOX can protect plants from various environmental stresses, especially high light stress. PTOX also plays significant roles in chloroplast development and plant morphogenesis. Global physiological roles played by PTOX could be a direct or indirect consequence of its PQH2 oxidase activity to maintain the PQ pool redox state on the thylakoid membrane. The PTOX-dependent chloroplast RETC (so-called chlororespiration) does not contribute significantly when chloroplast PETC is normally developed and functions well. However, PTOX-mediated RETC could be the major force to regulate the PQ pool redox balance in the darkness, under conditions of stress, in nonphotosynthetic plastids, especially in the early development from proplastids to chloroplasts.

Treatment intensification for patients with type 2 diabetes and poor glycaemic control.

AIMS: To identify the time to and patient characteristics associated with treatment intensification in patients with type 2 diabetes (T2D) and poor glycaemic control. METHODS: Using a large US insurance claims database, we conducted a retrospective cohort study among adult patients with T2D and glycated haemoglobin (HbA1c) ≥8% (index date) after ≥3 months of therapy including metformin. Patients were required to have continuous enrolment for at least 12 months before (baseline) and after index date, and no injectable antidiabetes medications. We defined treatment intensification as prescription fill for injectable or additional oral antidiabetic drugs (OADs). Cox modelling was performed to identify factors associated with time to treatment intensification. RESULTS: For the 11 525 patients meeting the inclusion criteria, the mean age at index date was 57 years, 40% were female and the mean index HbA1c was 9.1%. Overall, 37% of patients had their treatment intensified <6 months after, 11% had their treatment intensified 6-12 months after, and 52% did not have their treatment intensified <12 months after the index date. A higher index HbA1c was associated with early intensification [hazard ratio (HR) 1.18 for HbA1c ≥9 to <10% and HR 1.41 for HbA1c ≥10% compared with HbA1c ≥8 to <9%; p < 0.0001), and later line of therapy was associated with late intensification (HR 0.78 for metformin with one OAD and HR 0.68 for metformin with ≥2 OADs compared with metformin monotherapy; p < 0.0001). CONCLUSIONS: Fewer than half of patients with T2D and treatment failure received intensification within 12 months in a real-world US population. Factors associated with treatment inertia can be used to target clinical care for these patients.

Intestinal microbiota and oral administration of Enterococcus faecium associated with the growth performance of new-born piglets.

The oral administration of Enterococcus faecium EF1 to new-born suckling and weaning piglets along with their growth performances and intestinal microbiota was investigated in this study. Twenty-four new-born piglets were initially divided into 2 groups. The probiotics group received 2 ml of 10% sterilised skimmed milk by oral gavage supplemented with 6×10(8) cfu/ml viable E. faecium EF1 at the first, the third and the fifth day after birth, while the control group received 2 ml of 10% sterilised skimmed milk without probiotics at the same time. Results showed that oral administration of E. faecium EF1 was associated with a remarkable increase on the body weight of piglets for both suckling and weaning periods, by 30.73% (P<0.01) and 320.84% (P<0.01), and also decreased the diarrhoea rate, by 43.21% (P<0.05) and 71.42% (P<0.05), respectively. In addition, 454-pyrosequencing analysis revealed that there was no significant difference in the intestinal microbial diversity of the suckling piglets between the two groups; nevertheless, when compared to the control group, the relative abundance of Firmicutes in the probiotics group was substantially augmented, while the relative abundance of Proteobacteria, Bacteroidetes and Fusobacteria diminished. However, results indicated that oral administration of E. faecium EF1 did not have any influence on the relative abundance of Firmicutes in weaning piglets rather than increasing the relative abundance of Bacteroidetes and decreasing the relative abundance of Proteobacteria. Furthermore, at the level of the Firmicutes phylum, the relative abundance of Lactobacillales in the probiotic group increased significantly. These findings suggest that oral administration of E. faecium EF1 to new-born piglets could improve the growth performance and intestinal microbiota of piglets for both suckling and weaning periods.

Association between age at first sexual intercourse and knowledge, attitudes and practices regarding reproductive health and unplanned pregnancy: a cross-sectional study.

BACKGROUND: Age at first sexual intercourse (AFSI) is decreasing among adolescents in developed nations. An early sexual debut has been associated, to some extent, with multiple sexual partners, infrequent use of condoms, unplanned pregnancy, unsafe abortion, and sexually transmitted disease and human immunodeficiency virus infection. Unplanned pregnancy among adolescents has both physical and social adverse effects. METHODS: In total, 78,400 self-administered anonymous questionnaires were distributed to college students in seven cities in China to determine the age at which Chinese college students first engage in sexual activity, and the association between AFSI and knowledge, attitudes and practices (KAP) regarding reproductive health and unplanned pregnancy. RESULTS: Approximately 10,164 students reported that they were sexually active, and most reported that they had engaged in sexual intercourse for the first time during college. The average AFSI was 20.14 [standard deviation (SD) 2.98] years, and the average AFSI by gender was 19.97 (SD 2.97) years for males and 20.41 (SD 2.97) years for females. The unplanned pregnancy rate among the participants was 34.03%. Participants lacked knowledge about contraception and reproductive health, although most believed that it is necessary to have this knowledge. Participants' attitudes towards premarital sex were varied. Factors that were found to be associated with unplanned pregnancy were AFSI, contraceptive methods used for first sexual act, and whether contraceptive methods were used for every sexual act. CONCLUSIONS: The college period is a key time for Chinese students in terms of becoming sexually active. As such, comprehensive and informative reproductive health education should be provided before and during the college period. Furthermore, reproductive health education should include appropriate sexual morality education and comprehensive sex education. Gender traits and needs should be considered in sex education.