Sensitive and rapid identification of pathogens by droplet digital PCR in a cohort of septic patients: a prospective diagnostic study.

BACKGROUND: There is a critical need for a rapid and sensitive pathogen detection method for septic patients. This study aimed to investigate the diagnostic efficacy of Digital droplet polymerase chain reaction (ddPCR) in identifying pathogens among suspected septic patients. METHODS: We conducted a prospective pilot diagnostic study to clinically validate the multiplex ddPCR panel in diagnosing suspected septic patients. A total of 100 sepsis episodes of 89 patients were included in the study. RESULTS: In comparison to blood culture, the ddPCR panel exhibited an overall sensitivity of 75.0% and a specificity of 69.7%, ddPCR yielded an additional detection rate of 17.0% for sepsis cases overall, with a turnaround time of 2.5 h. The sensitivity of ddPCR in the empirical antibiotic treatment and the non-empirical antibiotic treatment group were 78.6% versus 80.0% (p > 0.05). Antimicrobial resistance genes were identified in a total of 13 samples. Whenever ddPCR detected the genes beta-lactamase-Klebsiella pneumoniae carbapenemase (blaKPC) or beta-lactamase-New Delhi metallo (blaNDM), these findings corresponded to the cultivation of carbapenem-resistant gram-negative bacteria. Dynamic ddPCR monitoring revealed a consistent alignment between the quantitative ddPCR results and the trends observed in C-reactive protein and procalcitonin levels. CONCLUSIONS: Compared to blood culture, ddPCR exhibited higher sensitivity for pathogen diagnosis in suspected septic patients, and it provided pathogen and drug resistance information in a shorter time. The quantitative results of ddPCR generally aligned with the trends seen in C-reactive protein and procalcitonin levels, indicating that ddPCR can serve as a dynamic monitoring tool for pathogen load in septic patients.

[The Effect of SIRT5 Deletion on Recovery of Hematopoietic Stem Cells after Injury in Mouse].

OBJECTIVE: To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells (HSCs) after treated by 5-FU in mouse. METHODS: Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells (HSPCs) in bone marrow (BM), the proportion of T cells, B cells and myeloid cells (TBM) in peripheral blood (PB) and spleen, and the development of T cells in thymus. Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle, apoptosis and the proportion of HSPCs in BM. The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro. RESULTS: SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice. SIRT5 deletion increased proportion of HSPCs in BM. After 5-FU treatment, the proportion of HSCs in SIRT5 deletion mice was significant decreased (P < 0.05), the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase (P < 0.05), and the proportion of early apoptosis increased (P < 0.05). By monoclonal culture in vitro, the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly (P < 0.05). CONCLUSION: SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro. SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.

The application of nanopore targeted sequencing for pathogen diagnosis in bronchoalveolar lavage fluid of patients with pneumonia: a prospective multicenter study.

OBJECTIVE: To evaluate the value of nanopore targeted sequencing in diagnosing pneumonia pathogens. METHODS: This large-scale multicentre prospective study performed in 8 hospitals across China from April to October 2022. Hospitalised patients with a diagnosis of pneumonia at admission were included. Complete clinical data were collected, and bronchoalveolar lavage fluid were obtained from each patient. These samples underwent simultaneous testing using conventional microbial testing, metagenomic next-generation sequencing, and nanopore targeted sequencing. RESULTS: A total of 218 patients were included. Among the 168 cases of pulmonary infection, 246 strains of pathogens were confirmed. Nanopore targeted sequencing outperformed conventional microbial testing, identifying more pathogens with a sensitivity increase of 47.9% (77.2% vs. 29.3%). Metagenomic next-generation sequencing had a sensitivity of 82.9%. Total of 70.1% patients had consistent results in both metagenomic next-generation sequencing and nanopore targeted sequencing. Nanopore targeted sequencing exhibited significantly higher sensitivity in detecting Pneumocystis jiroveci, cytomegalovirus, Mycobacterium tuberculosis, Nontuberculous mycobacteria, Streptococcus pneumoniae, and Mycoplasma pneumoniae compared to conventional microbial testing. However, metagenomic next-generation sequencing demonstrated higher sensitivity than nanopore targeted sequencing for Aspergillus (88.5% vs. 53.8%). Regarding the detection of co-infections, nanopore targeted sequencing displayed significantly higher sensitivity than conventional microbial testing (76.7% vs. 28.7%) and was on par with metagenomic next-generation sequencing (76.7% vs. 82.9%). CONCLUSION: Nanopore targeted sequencing performs equally well as metagenomic next-generation sequencing in bronchoalveolar lavage fluid for pathogen diagnosis in pneumonia, both methods showing higher sensitivity than conventional microbial testing. Nanopore targeted sequencing can be considered a reliable method for diagnosing pathogens in pneumonia.

[Effect of Hemoglobin on Efficacy of CAR-T Therapy in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, ß2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION: The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.

Patchouli alcohol protects against myocardial ischaemia-reperfusion injury by regulating the Notch1/Hes1 pathway.

CONTEXT: Patchouli alcohol (PA) has protective effects on cerebral ischaemia/reperfusion (I/R) injury, but its efficacy on myocardial ischaemia-reperfusion (MI/R) has yet to be addressed. OBJECTIVE: To examine the therapeutic effect of PA on myocardial ischaemia-reperfusion (I/R) injury. MATERIALS AND METHODS: C57BL/6 male mice were randomly divided into sham, MI/R, MI/R + PA-10, MI/R + PA-20 and MI/R + PA-40 groups. In vivo MI/R model was established by ligating the anterior descending coronary artery of the heart. In vitro stimulated IR cell model was constructed by using the rat cardiomyocyte H9C2 cell line. Mice in the treatment groups were intraperitoneally injected with PA (10, 20, 40 mg/kg) for 30 days then subjected to surgery, and cells in the experimental group were pre-treated with PA (1, 10 or 100 µmol/L). After treatment, mouse heart function, myocardial injury markers, myocardial infarction and Notch1/Hes1 expression, endoplasmic reticulum stress markers, and apoptosis-related proteins were determined. RESULTS: In vivo, PA treatment improved hemodynamic parameter changes and myocardial enzymes, increased the left ventricular ejection fraction and left ventricular fractional shortening, reduced the left ventricular end-systolic diameter and inhibited CK-MB, cTnI and cTnT levels. In addition, PA attenuated myocardial tissue damage and apoptosis. PA treatment elevated Notch1, NICD and Hes1 levels and suppressed the levels of ATF4, p-PERK/PERK, and cleaved caspase-3/caspase-3 in vitro and in vivo. DISCUSSION AND CONCLUSION: PA protects against MI/R, possibly by modulating ER stress, apoptosis and the Notch1/Hes1 signalling pathways. These findings indicate that PA may be a promising candidate for treating ischaemic heart diseases.

Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits.

The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied. Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (MEC)-CA1 pathway, as well as the structural integrity of CA1 pyramidal neurons were markedly impaired in adulthood. These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the MEC and nectin3 level in the CA1. Postnatal suppression of nectin1 but not nectin3 level in the MEC impaired spatial memory, whereas conditional inactivation of nectin1 from MEC excitatory neurons reproduced the adverse effects of early-life stress on MEC-dependent memories and neuronal plasticity in CA1. Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits.

Cholinergic neurons in the pedunculopontine nucleus guide reversal learning by signaling the changing reward contingency.

Cognitive flexibility enables effective switching between mental processes to generate appropriate responses. Cholinergic neurons (CNs) within the pedunculopontine nucleus (PPN) are associated with many functions, but their contribution to cognitive flexibility remains poorly understood. Here we measure PPN cholinergic activities using calcium indicators during the attentional set-shifting task. We find that PPN CNs exhibit increasing activities correlated with rewards during each stage and error trials in reversal stages, indicating sensitivity to rule switching. Inhibition of PPN cholinergic activity selectively impairs reversal learning, which improves with PPN CN activation. Activation of PPN CNs projecting to the substantia nigra pars compacta, mediodorsal thalamus, and parafascicular nucleus in a time-locked manner with reward improves reversal learning. Therefore, PPN CNs may encode not only reward signals but also the information of changing reward contingency that contributes to guiding reversal learning through output projections to multiple nuclei that participate in flexibility.

Highly Efficient Inverted Organic Light-Emitting Diodes Adopting a Self-Assembled Modification Layer.

Inverted organic light-emitting diodes (IOLEDs) can be integrated with low-cost n-channel thin-film transistors for use in active-matrix OLEDs (AMOLEDs). However, the electron injection from conventional indium tin oxide (ITO) cathode to the upper electron transport layer usually suffers from a large injection barrier. To improve the electron injection efficiency, the electron injection layers (EILs) of ZnO modified by a self-assembled monolayer arginine (Arg) were developed to construct efficient IOLEDs. ZnO/Arg EILs present an ultralow work function (WF) of 2.35 eV, which is lower than that of ZnO modified by poly(ethylenimine) (PEI) (2.77 eV). The mechanism of low WF is attributed to the generation of strong molecular dipoles and interface dipoles at the interface of ZnO/Arg. The green fluorescent IOLEDs with ZnO/Arg present a low turn-on voltage (Von) of 3.5 V and a maximum current efficiency (CEmax) of 4.5 cd/A. Especially, the device possesses a half-life of 3600 h at an initial luminance of 1700 cd/m2, which is 36 times as long as that of the IOLEDs with ZnO/PEI as EILs. Furthermore, the green phosphorescent IOLEDs show a Von of 3.5 V, a CEmax of 59.1 cd/A, and a maximum external quantum efficiency (EQEmax) of 16.8%. At a luminance of 10 000 cd/m2, the efficiency roll-off of the device is only 6.3%.

Enhanced Identification of Novel Potential Variants for Appendicular Lean Mass by Leveraging Pleiotropy With Bone Mineral Density.

Strong relationships have been found between appendicular lean mass (ALM) and bone mineral density (BMD). It may be due to a shared genetic basis, termed pleiotropy. By leveraging the pleiotropy with BMD, the aim of this study was to detect more potential genetic variants for ALM. Using the conditional false discovery rate (cFDR) methodology, a combined analysis of the summary statistics of two large independent genome wide association studies (GWAS) of ALM (n = 73,420) and BMD (n = 10,414) was conducted. Strong pleiotropic enrichment and 26 novel potential pleiotropic SNPs were found for ALM and BMD. We identified 156 SNPs for ALM (cFDR <0.05), of which 74 were replicates of previous GWASs and 82 were novel SNPs potentially-associated with ALM. Eleven genes annotated by 31 novel SNPs (13 pleiotropic and 18 ALM specific) were partially validated in a gene expression assay. Functional enrichment analysis indicated that genes corresponding to the novel potential SNPs were enriched in GO terms and/or KEGG pathways that played important roles in muscle development and/or BMD metabolism (adjP <0.05). In protein-protein interaction analysis, rich interactions were demonstrated among the proteins produced by the corresponding genes. In conclusion, the present study, as in other recent studies we have conducted, demonstrated superior efficiency and reliability of the cFDR methodology for enhanced detection of trait-associated genetic variants. Our findings shed novel insight into the genetic variability of ALM in addition to the shared genetic basis underlying ALM and BMD.

Identification of Hepatic Steatosis in Premenopausal and Postmenopausal Women Based on Phenotypes Combining Triglyceride Levels and Anthropometric Indices: A Cross-Sectional Study.

BACKGROUND: The hypertriglyceridemic waist phenotype (HWP) has exhibited a strong association with metabolic syndrome, a condition closely linked with nonalcoholic fatty liver disease (NAFLD). However, no study has investigated whether the HWP can accurately predict NAFLD among premenopausal and postmenopausal women or whether alternative anthropometric indexes could replace waist circumference (WC) in the HWP. We examined the power of phenotypes combining triglyceride (TG) levels with anthropometric indexes such as body mass index (BMI), WC, waist-to-hip ratio, waist-to-height ratio, and percent body fat, to detect NAFLD among premenopausal and postmenopausal women. METHODS: We conducted a cross-sectional study of 1125 premenopausal women and 654 postmenopausal women who had received an annual health checkup. For all the participating women, we measured both anthropometric and biochemical indexes, such as serum lipid levels. NAFLD diagnoses were made on the basis of abdominal ultrasonography findings. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the indicators' ability to detect NAFLD. RESULTS: Among the indicators of hepatic steatosis, the combined phenotypes of TG level (≥1.50 mmol/L) and BMI (≥24.0 kg/m2) exhibited the largest AUC (0.841, 95%confidence interval [CI] 0.812-0.871, P< 0.001) for premenopausal women, whereas WC alone exhibited the highest predictive potential (0.765, 95% CI 0.729-0.801, P< 0.001) for postmenopausal women. CONCLUSION: Out of all the phenotypes combining a single anthropometric index with TG level or WC and TG level, the combination of TG level and BMI was the best indicator of NAFLD for premenopausal women. For screening NAFLD in postmenopausal women, WC alone was superior to all other indicators.

Is Iba-1 protein expression a sensitive marker for microglia activation in experimental diabetic retinopathy?

AIM: To investigate the changes of Iba-1 and other potential markers for microglia activation in experimental diabetic retinopathy (DR). METHODS: Male Sprague-Dawley rats were rendered diabetes via intraperitoneal injection of streptozotocin. The retinas were harvested at 1 to 24wk after diabetes onset. Hypoxia-treated mouse microglial cell line (BV2 cells) was employed as the in vitro model to mimic diabetic condition. The expressions of Iba-1, CD11b, ICAM-1 as well as the inflammatory factors were examined with real-time polymerase chain reaction, Western blot and immunofluorescence both in vivo and in vitro. RESULTS: Compared with age-matched normal control, the number of microglia (Iba-1 positive immunostaining) in diabetic rat retinas was increased from 1 to 24wk of diabetes, which was most obvious at 12wk of diabetes. Iba-1 protein expression detected by Western blot was increased slightly in diabetic rat retinas compared with that in age-matched normal control; however, there was statistically significant between two groups only at 2wk after diabetes onset. The mRNA expression of Iba-1 was decreased significantly at 2 and 4wk of diabetic rat retinas, and remained unchanged at 8 and 12wk of diabetes. In BV2 cells, there was no significant change for the Iba-1 protein expression between normoxia and hypoxia groups; however, its mRNA level was decreased significantly under hypoxia. To further characterize microglial activation, F4/80, CD11b and inflammatory factors were detected both in vivo and in vitro. Compared with normal control, the expressions of F4/80 and CD11b as well as the inflammatory factors, such as ICAM-1, iNOS, COX2, IL-1ß and IL-6, were increased significantly both in vivo and in vitro. CONCLUSION: Iba-1 protein expression might not be a sensitive marker to evaluate the activation of microglia in experimental DR. However, Iba-1 immunostaining, in combination with other markers like CD11b and ICAM-1, could be well reflect the activation of microglia. Thus, it is of great importance to explore other potential marker to evaluate the activation of microglia.

The HIF-1α/p53/miRNA-34a/Klotho axis in retinal pigment epithelial cells promotes subretinal fibrosis and exacerbates choroidal neovascularization.

Wet age-related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti-vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) increases the stability and activation of p53, which activates microRNA-34a (miRNA-34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA-34a that inhibits fibrosis. This study aimed to explore the role of the HIF-1α/p53/miRNA-34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia-induced HIF-1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE-19 cells (a human RPE cell line). HIF-1α-dependent p53 activation up-regulated miRNA-34a expression in ARPE-19 cells following hypoxia. Moreover, hypoxia-induced p53-dependent miRNA-34a inhibited the expression of Klotho in ARPE-19 cells. Additionally, the HIF-1α/p53/miRNA-34a/Klotho axis facilitated hypoxia-induced EMT in ARPE-19 cells. In vivo, blockade of the HIF-1α/p53/miRNA-34a/Klotho axis alleviated the formation of mouse laser-induced CNV and subretinal fibrosis. In short, the HIF-1α/p53/miRNA-34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.

Screening for Metabolic Syndrome Using an Integrated Continuous Index Consisting of Waist Circumference and Triglyceride: A Preliminary Cross-sectional Study.

BACKGROUND: It has been suggested that hypertriglyceridemic waist (HW) phenotype is strongly associated with metabolic syndrome (MetS); however, there are very limited studies integrating triglyceride (TG) and waist circumference (WC) into a continuous variable to investigate the predictive power of this phenotype. Inspired from the triglyceride glucose index (TyG), we developed an integrated continuous index termed waist-triglyceride index (WTI) which was calculated as Ln [TG (mg/dl) WC (cm)/2]. OBJECTIVE: We aimed to examine the potential of WTI in screening for MetS by comparing this quantitative index with the qualitative HW phenotype and other frequently used indices. METHODS: A cross-sectional study was conducted in a total of 3460 non-diabetic adults who participated in an annual health checkup. MetS was defined by the update National Cholesterol Education Program/Adult Treatment Panel ш criteria for Asian Americans. Receiving operating characteristic (ROC) curve and areas under the curve (AUC) were employed to evaluate the performance of the involved indices in screening for MetS. Statistical differences among the AUC values of the indices were compared. RESULTS: In both genders, the AUC value of WTI, TyG or HW phenotype was markedly larger than that of each anthropometric index alone. In men, there were no statistical differences in the AUC values among WTI, TyG and HW phenotype, whereas in women, the AUC value of WTI was significantly larger than that of HW phenotype [difference between area (DBA): 0.042, 95% CI: 0.0224-0.0617, P < 0.0001] and was nominally and significantly smaller than that of TyG (DBA: 0.00646, 95% CI: 0.000903-0.012, P = 0.0227). CONCLUSION: Our results suggest that there are discriminatory performance between the WTI and HW phenotype in the detection of MetS in women rather than in men. Appropriate markers for screening MetS in population study should be considered according to the genders.

The Petri Dish-N2B27 Culture Condition Maintains RPE Phenotype by Inhibiting Cell Proliferation and mTOR Activation.

OBJECTIVE: To develop a method for the rapid isolation of rat RPE cells with high yield and maintain its epithelial state in modified culture system. METHODS: The eyeballs were incubated with dispase. The retina was isolated with RPE attached and cut into several pieces. Following a brief incubation in growth medium, large RPE sheets can be harvested rapidly. RPE cells were divided into four groups and cultured for several weeks, that is, (1) in cell culture dishes with 10% FBS containing medium (CC dish-FBS), (2) in petri dishes with 10% FBS containing medium (Petri dish-FBS), (3) in cell culture dishes with N2 and B27 containing medium (CC dish-N2B27), and (4) in petri dishes with N2 and B27 containing medium (Petri dish-N2B27). Morphological and biological characteristics were investigated using light microscopy, Q-PCR, and western blot. RESULTS: The retina would curl inwardly during the growth medium incubation period, releasing RPE sheets in the medium. Compared with low density group (5,000 cells/cm2), RPE cells plated at high density (15,000 cells/cm2) can maintain RPE morphology for a more extended period. Meanwhile, plating RPE cells at low density significantly reduced the expression of RPE cell type-specific genes (RPE65, CRALBP, and bestrophin) and increased the expression of EMT-related genes (N-cadherin, fibronectin, and α-SMA), in comparison with the samples from the high density group. The petri dish culture condition reduced cell adhesion and thus inhibited RPE cell proliferation. As compared with other culture conditions, RPE cells in the petri dish-N2B27 condition could maintain RPE phenotype with increased expression of RPE-specific genes and decreased expression of EMT-related genes. The AKT/mTOR pathway was also decreased in petri dish-N2B27 condition. CONCLUSION: The current study provided an alternative method for easy isolation of RPE cells with high yield and maintenance of its epithelial morphology in the petri dish-N2B27 condition.

Elevated vitreous Lipocalin-2 levels of patients with proliferative diabetic retinopathy.

BACKGROUND: Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. This study aims to assess the concentrations of LCN2 and vascular endothelial growth factor (VEGF) expressed in the vitreous humors of patients with proliferative diabetic retinopathy (PDR). METHODS: The concentrations of LCN2 and VEGF were measured from the vitreous of 67 patients undergoing vitrectomy (20 controls and 47 PDR) via enzyme-linked immunosorbent assay (ELISA). Patients with non-ocular pathology that could elevate the LCN2 level in the vitreous were excluded. PDR activity and a history of panretinal photocoagulation were used for further grouping analysis. RESULTS: The vitreous concentration of LCN2 was statistically significantly higher in the PDR group compared to the control group (63,522 (30,009) pg/ml versus 1663 (1191) pg/ml, respectively; P < 0.001). VEGF level was also significantly higher in the PDR group than in the control group (1038 (1326) pg/ml versus 9 pg/ml, respectively; P < 0.001). The mean vitreous LCN2 and VEGF levels in active PDR patients were significantly higher than that of the inactive PDR patients. The mean LCN2 concentration in vitreous humor was significantly lower in the 28 PDR patients with a history of complete PRP (37,304 (16,651) pg/mL) in comparison with 19 PDR patients without preperformed panretinal photocoagulation or with preperformed incomplete panretinal photocoagulation (79,796 (24,391) pg/mL). A significant correlation between the vitreous LCN2 level and VEGF level was found in patients with PDR (R = 0.34; P = 0.019). CONCLUSIONS: This report shows a significant increase of LCN2 in the vitreous fluid of patients with PDR and present a significant correlation between LCN2 and VEGF, suggesting LCN2 might be involved in the pathogenesis of PDR.

Anxiolytic Effect of Increased NREM Sleep after Acute Social Defeat Stress in Mice.

Social defeat stress (SDS) plays a major role in the pathogenesis of psychiatric disorders like anxiety and depression. Sleep is generally considered to involve recovery of the brain from prior experience during wakefulness and is altered after acute SDS. However, the effect of acute SDS on sleep/wake behavior in mice varies between studies. In addition, whether sleep changes in response to stress contribute to anxiety is not well established. Here, we first investigated the effects of acute SDS on sleep/wake states in the active period in mice. Our results showed that total sleep time (time in rapid eye-movement [REM] and non-REM [NREM] sleep) increased in the active period after acute SDS. NREM sleep increased mainly during the first 3 h after SDS, while REM sleep increased at a later time. Then, we demonstrated that the increased NREM sleep had an anxiolytic benefit in acute SDS. Mice deprived of sleep for 1 h or 3 h after acute SDS remained in a highly anxious state, while in mice with ad libitum sleep the anxiety rapidly faded away. Altogether, our findings suggest an anxiolytic effect of NREM sleep, and indicate a potential therapeutic strategy for anxiety.

MicroRNA-24 protects retina from degeneration in rats by down-regulating chitinase-3-like protein 1.

MicroRNAs (miRNAs) have been shown to play critical roles in the pathogenesis and progression of degenerative retinal diseases like age-related macular degeneration (AMD). In this study, we first demonstrated that miR-24 plays an important role in maintaining retinal structure and visual function of rats by targeting chitinase-3-like protein 1 (CHI3L1). In the retinal pigment epithelial (RPE) cells of Royal College of Surgeons (RCS) rats, an animal model of genetic retinal degeneration (RD), miR-24 was found lower and CHI3L1 level was higher in comparison with those in Sprague-Dawley (SD) rats. Other changes in the eyes of RCS rats include activated AKT/mTOR and ERK pathways and abnormal autophagy in the RPE cells. Such roles of miR-24 and CHI3L1 were further confirmed in RCS rats by subretinal injection of agomiR-24, which decreased CHI3L1 level and preserved retinal structure and function. Upstream, NF-κB was identified as the regulator of miR-24 in the RPE cells of these rats. On the other hand, in SD rats, intraocular treatment of antagomiR-24 induced pathological changes similar to those in RCS rats. The results revealed the protective roles for miR-24 to RPE cells and a mechanism for RD in RCS rats was proposed: extracellular stress stimuli first activate the NF-κB signaling pathway, which lowers miR-24 expression so that CHI3L1 increased. CHI3L1 sequentially results in aberrant autophagy and RPE dysfunction by activating AKT/mTOR and ERK pathways. Taken together, although the possibility, that the therapeutic effects in RCS rats are caused by other transcriptional changes regulated by miR-24, cannot be excluded, these findings indicate that miR-24 protects rat retina by targeting CHI3L1. Thus, miR-24 and CHI3L1 might be the targets for developing more effective therapy for degenerative retinal diseases like AMD.

Prognostic Values of Serum Chloride and Sodium Levels in Patients with Three-vessel Disease.

OBJECTIVE: Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD. METHODS: We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients. RESULTS: A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score. CONCLUSION: Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.

Utility of different indices in screening Chinese postmenopausal women for hepatic steatosis.

BACKGROUND AND OBJECTIVES: To analyze the potential of fatty liver index (FLI) and several obesity indices and to explore which index is best for predicting nonalcoholic fatty liver disease (NAFLD) in Chinese postmenopausal women. METHODS AND STUDY DESIGN: A cross-sectional study was conducted in 680 Chinese postmenopausal women. NAFLD was defined as a hepatic steatosis observed on liver ultrasonography in the absence of a second cause. Odds ratio and corresponding 95% confidence interval (CI) between hepatic steatosis and FLI as well as different obesity indices were evaluated by Binary Logistic regression model. Receiver operating characteristic curve and area under curve (AUC) were used to compare the ability of predicting hepatic steatosis between FLI and obesity indices. RESULTS: The upper values of all indices were significantly associated with the presence of hepatic steatosis (all p<0.01) after the adjustment for potential confounders. The largest AUC [0.85 (0.82-0.88), 95% CI, p<0.01] was observed for FLI, followed by the frequently used obesity indices. CONCLUSIONS: FLI is closely associated with the presence of hepatic steatosis in Chinese postmenopausal women. Compared to the obesity indices frequently used, FLI is a better surrogate marker for predicting the presence of hepatic steatosis in Chinese postmenopausal women.

Natural sunlight driven highly efficient photocatalysis for simultaneous degradation of rhodamine B and methyl orange using I/C codoped TiO2 photocatalyst.

Increasing the efficiency of dye degradation is a critical issue for the application for photocatalysis. It is one of the greatest challenges to enhance the utilization of photo generated carriers in semiconductor, especially for sunlight irradiation. In this study, I/C-codoped TiO2 was synthesized by a simple solvothermal-calcination method. The codoping interstitial carbon and substitutional iodine not only widened the light absorption range of the TiO2 photocatalysts, but also enhanced the separation of photo-induced carriers. The photocatalytic activities of RhB and MO degradation over the 4-I/C-TiO2 photocatalyst could reach 98.2% and 94.2% after 25 min visible light irradiation (λ ≥ 400 nm), respectively. Notably, 4-I/C-TiO2 showed good activity for MO and RhB mixed degradation and could also accomplish the photocatalytic degradation in the above mixed system under natural sunlight irradiation. According to the dark catalytic experiment, I/C-codoping could effectively accelerate the formation of hydroxyl radicals from the generated H2O2, which was formed for the enhanced photocatalytic activity of dye degradation. The gained knowledge may provide some insights into the photocatalytic degradation over the codoped TiO2 catalyst.