Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Background: Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. Methods: A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Results: Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Conclusion: Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

Effects of Supplementing Tributyrin on Meat Quality Characteristics of Foreshank Muscle of Weaned Small-Tailed Han Sheep Lambs.

This experiment aimed to evaluate the effects of supplementing tributyrin (TB) on the meat quality characteristics of foreshank muscle of weaned lambs. A total of 30 healthy weaned Small-Tailed Han female lambs with body weights ranging from 23.4 to 31.6 kg were selected and randomly divided into five groups, and each group consisted of 6 lambs. The control group was fed a basic total mixed ration, while other groups were fed the same ration supplemented with 0.5, 1.0, 2.0, and 4.0 g/kg TB, respectively. The experiment lasted 75 d, including 15 d of adaptation. Foreshank muscle obtained at the same position from each lamb was used for chemical analysis and sensory evaluation. The results showed that supplementing TB increased the muscle contents of ether extract (p = 0.029), calcium (p = 0.030), phosphorus (p = 0.007), and intermuscular fat length (p = 0.022). Besides, TB increased the muscle pH (p = 0.001) and redness (p < 0.001) but reduced the lightness (p < 0.001), drip loss (p = 0.029), cooking loss (p < 0.001), shear force (p = 0.001), hardness (p < 0.001), cohesiveness (p < 0.001), springiness (p < 0.001), gumminess (p < 0.001), and chewiness (p < 0.001). In addition, TB increased the muscle content of inosine-5'-phosphate (p = 0.004). Most importantly, TB increased the muscle contents of essential amino acids (p < 0.001). Furthermore, TB increased the saturated fatty acids level in the muscle (p < 0.001) while decreasing the unsaturated fatty acids content (p < 0.001). In conclusion, supplementing TB could influence the meat quality of foreshank muscle of weaned lambs by modifying the amino acid and fatty acid levels.

Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia.

The treatment of B cell malignancies has dramatically changed with the introduction of immunotherapy, especially chimeric antigen receptor T (CAR-T) cell therapy. However, only limited efficacy is observed in acute myeloid leukaemia (AML). In the study, We detected CD123 and CLL-1 expression on leukaemia cells from Relapsed/Refractory AML (R/R AML) patients. Then, we constructed anti-CD123 CAR and CLL-1 CAR with different co-stimulation domains (CD28 or 4-1BB) and detected their anti-AML effects. To increase the efficacy of CAR-T cell therapy, we tested different strategies, including application of combined checkpoint inhibitors and histone deacetylase inhibitors (HDACi) in vivo and in vitro We found CD123 and CLL-1 were highly expressed on AML cells. The proportions of T cell subsets and NK cells involved in anti-tumour or anti-inflammation processes in AML patients significantly decreased when compared with healthy donors. Both CD123 CAR and CLL-1 CAR displayed specific anti-AML effects in vitro To improve the lysis effects of CAR-T cells, we combined CAR-T cell therapy with different agents. PD-1/PD-L1 antibodies only slightly improved the potency of CAR-T cell therapy (CD123 CAR-T 60.92% ± 2.9087% vs. 65.43% ± 2.1893%, 60.92% ± 2.9087% vs. 67.43% ± 3.4973%; 37.37% ± 3.908% vs. 41.89% ± 5.1568%, 37.37% ± 3.908% vs. 42.84% ± 4.2635%). However, one HDACi (valproic acid [VPA]) significantly improved CAR-T cell potency against AML cells (CLL-1 CAR-T 34.97% ± 0.3051% vs. 88.167% ± 1.5327%, p < 0.0001; CD123 CAR-T 26.87% ± 2.7010% vs. 82.56% ± 3.086%, p < 0.0001 in MV411; CLL-1 CAR-T 78.77% ± 1.2061% vs. 93.743% ± 1.2333%, p < 0.0001; CD123 CAR-T 64.10% ± 1.5130% vs. 94.427% ± 0.142%, p = 0.0001 in THP-1). Combination therapy prolonged the overall survival of mice when compared with single CD123 CAR-T cell therapy (median survival: 180 days vs. unfollowed). A possible mechanism is that activated CD8+T cells upregulate natural-killer group 2 member D (NKG2D), and VPA upregulates NKG2D ligand expression in AML cells, contributing to NKG2D-mediated cytotoxicity of CAR-T cells against tumour cells. In conclusion, CD123 and CLL-1 are promising targets for AML CAR-T cell therapy. A combination of VPA pre-treatment and CAR-T against AML exhibits synergic effects.

Super multi-view display based on near-eye pinholes.

Vergence-accommodation-conflict-free super multi-view (SMV) display based on more than one near-eye pinhole group for each pupil of the viewer is developed in this paper. Two-dimensionally arranged pinholes of a group correspond to different subscreens of the display screen, with perspective views projected by each subscreen through a corresponding pinhole splicing into an image of enlarged field of view (FOV). By sequentially switching on/off different pinhole groups, more than one mosaic image is projected to each pupil of the viewer. Adjacent pinholes of a group are endowed with different timing-polarizing characteristics to generate an effective noise-free region for each pupil. In the experiment, four groups of 3×3 pinholes are configured for a proof-of-concept SMV display on a 240 Hz display screen, with a diagonal FOV of 55 deg and a depth of field reaching 1.2 m.

Super multi-view near-eye virtual reality with directional backlights from wave-guides.

Directional backlights have often been employed for generating multiple view-zones in three-dimensional (3D) display, with each backlight converging into a corresponding view-zone. By designing the view-zone interval for each pupil smaller than the pupil's diameter, super multi-view (SMV) can get implemented for a VAC-free 3D display. However, expanding the backlight from a light-source to cover the corresponding display panel often needs an extra thickness, which results in a thicker structure and is unwanted by a near-eye display. In this paper, two wave-guides are introduced into a near-eye virtual reality (NEVR) system, for sequentially guiding more than one directional backlight to each display panel for SMV display without bringing obvious extra thickness. A prototype SMV NEVR gets demonstrated, with two backlights from each wave-guide converging into two view-zones for a corresponding pupil. Although the additional configured light-sources are positioned far from the corresponding wave-guide in our proof-of-concept prototype, multiple light-sources can be attached to the corresponding wave-guide compactly if necessary. As proof, a 3D scene with defocus-blur effects gets displayed. The design range of the backlights' total reflection angles in the wave-guide is also discussed.

Evaluating the Effects of Replacing Alfalfa with Broussonetia papyrifera Branch/Leaf Powder on Growth and Serum Indicators in Dezhou Donkeys.

The purpose of this experiment was to study the apparent digestibility and the effects of Broussonetia papyrifera (BP) branch/leaf powder supplementation on growth performance and serum indicators in donkeys. The results showed that the apparent digestibility of dry matter (DM), crude protein (CP), crude fiber (CF), neutral detergent fiber (NDF), acidic detergent fiber (ADF), and digestible energy content (DE) of BP branch/leaf powder were 51.88%, 67.27%, 64.86%, 49.59%, 54.73%, 40.87%, and 6.37 MJ/kg, respectively. The average daily gain (ADG) in the 20% group was significantly higher than in the 0% and 30% groups. The serum albumin (ALB) levels in the 0% and 10% groups were significantly higher than those in the 20% and 30% groups, while the serum globulin (GLB) content in the 10% group was significantly lower than in the other groups. The 20% group showed decreased serum triglyceride (TG) levels compared to the other groups. Both the 20% and 30% groups exhibited lower total cholesterol (TC) levels and increased alanine aminotransferase (ALT) compared to the 0% and 10% groups and higher serum lactate dehydrogenase (LDH) levels than the 10% group. The 30% group had higher serum immunoglobulin A (IgA) levels than the other groups, while all three BP branch/leaf powder groups had lower serum tumor necrosis factor (TNF-α) levels than the 0% group. There was a gradual increase in serum total antioxidant capacity (T-AOC) with the increasing amount of BP branch/leaf powder added. In conclusion, the optimal supplemental proportion of BP branch/leaf powder in the diet is 20%. Furthermore, BP branch/leaf powder can improve growth performance, serum immune indices, and antioxidant capacity in Dezhou donkeys.

Rhizomucor pusillus Infection in a Patient with Acute Myeloid Leukaemia After Haematopoietic Stem Cell Transplantation: Clinical Impact of Metagenomics Next-Generation Sequencing.

Long-term chemotherapy and immunosuppressants in acute myeloid leukaemia (AML) patients can result in a high risk of opportunistic infections. Rhizomucor pusillus is an opportunistic pathogen that exists in nature, but infection caused by R. pusillus is rare in the clinic. Notably, the sensitivity and detection time of conventional diagnostic tools for this fungus usually falls short of the needs of clinical diagnosis, resulting in treatment failure. Currently, metagenomics next-generation sequencing (mNGS) has played an important role in the detection of pathogens. Here, we report a case of R. pusillus pneumonia in a haematopoietic stem cell transplantation (HSCT) patient, detected by the mNGS method.

Co-evolutionary adaptations of Acinetobacter baumannii and a clinical carbapenemase-encoding plasmid during carbapenem exposure.

OXA-23 is the predominant carbapenemase in carbapenem-resistant Acinetobacter baumannii. The co-evolutionary dynamics of A. baumannii and OXA-23-encoding plasmids are poorly understood. Here, we transformed A. baumannii ATCC 17978 with pAZJ221, a bla OXA-23-containing plasmid from clinical A. baumannii isolate A221, and subjected the transformant to experimental evolution in the presence of a sub-inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of bla OXA-23 in pAZJ221, interfering allele dynamics, and chromosomal locus-level parallelism were observed. To characterize genotype-to-phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3' → 5') GMP-metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of bla OXA-23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of bla OXA-23 increased host fitness under carbapenem pressure but imposed a burden on the host in antibiotic-free media relative to the ancestral pAZJ221. Overall, our study provides a framework for the co-evolution of A. baumannii and a clinical bla OXA-23-containing plasmid in the presence of imipenem, involving early bla OXA-23 duplication followed by chromosomal adaptations that improved the fitness of plasmid-carrying cells.

Anti-breast cancer sinomenine derivatives via mechanisms of apoptosis induction and metastasis reduction.

Sinomenine, a morphinane-type isoquinoline-derived alkaloid, was first isolated from stems and roots of Sinomenium diversifolius (Miq.) in 1920. Later discovery by researchers confirmed various essential biological efficacy sinomenine exerted in vitro and in vivo. In this study, a series of 15 sinomenine/furoxan hybrid compounds were designed and synthesised in search of a TNBC drug candidate. Some of the target compounds exhibited strong antiproliferative activities against cancer cell lines, especially for TNBC cells, compared to positive controls. Among them, hybrid 7Cc exerted superior cytotoxic effects on cancer cell lines with exceptionally low IC50 (0.82 µM) against MDA-MB-231 cells with the highest safety index score. Further studies in mechanism displayed that 7Cc could induce an S phase cell cycle arrest, stimulate apoptosis in MDA-MB-231 cells, disrupt mitochondrial membrane potential and exert a genotoxic effect on DNA in cancer cells. In addition, 7Cc also notably inhibited MDA-MB-231 cells in both migration, invasion and adhesion.

Serum PTH Associated with Malnutrition Determined by Bioelectrical Impedance Technology in Chronic Kidney Disease Patients.

Purpose: Chronic malnutrition and cachexia are common in chronic kidney disease (CKD), and importance should be given to these complications because they affect the patient's quality of life and prognosis. This study analyzed the correlation between the serum PTH level, nutritional status, and body composition of patients with CKD. Methods: CKD patients were enrolled in Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, from December 1, 2016, to November 30, 2020. Bioelectrical impedance technology was applied to estimate the body composition. The characteristics of the body composition were compared among different stages of CKD patients, and then the correlation between PTH and body composition was analyzed. Results: 205 CKD patients were enrolled. Twenty-five patients were in stage 1 or 2 of CKD, 78 patients were in stage 3 or 4, 31 patients were in stage 5 without dialysis (referred to as CKD stage 5A), and 71 patients were in stage 5 with dialysis (referred to as CKD stage 5B). Body composition analysis showed that the patients had a phase angle (PA) of 5.02 ± 1.07°, a percentage of body fat (PBF) of 27.74 ± 8.8%, and a skeletal muscle mass index (SMI) of 7.4 ± 1.34 kg/m2. PBF peaked in the CKD stage 3/4 group and gradually decreased with the progression of CKD. The PA and SMI differed significantly between the CKD stage 1/2 and stage 5B groups. The proportion of low SMI did not differ significantly between the CKD stage 1/2 and stage 3/4 groups, but it was obviously higher in the CKD stage 5A and 5B groups. PTH was significantly correlated with BMI, hemoglobin, albumin, total cholesterol, triglycerides, and SMI. Binary logistic regression of low SMI showed that the odds ratio for PTH levels was greater than the upper limit of the normal range, which was 11.769 (p=0.043, 95% confidence interval: 1.078-128.536), and the model predictive power was 0.986 after correction for age, sex, height, weight, hemoglobin, serum calcium, serum phosphorus, serum total cholesterol, serum triglyceride, and basal metabolic rate. Conclusions: Bioelectrical impedance analysis might be useful in estimating the nutritional status of CKD patients in terms of fat and muscle parameters. High levels of PTH are an independent risk factor for developing low SMI in CKD patients.

Polarization enlargement of FOV in Super Multi-view display based on near-eye timing-apertures.

With strip-type timing-apertures attached to each eye of a viewer, more than one perspective views can be guided to either eye sequentially through different timing-apertures, thus implementing VAC-free (vergence-accommodation conflict-free) SMV (Super Multi-view) 3D (three-dimensional) display. To overcome the FOV (field of view) limitation problem due to small size of the timing-apertures along their arrangement direction, novel polarization architectures are designed to the timing-apertures in this paper. Correspondingly, the display screen of the proposed SMV display system is divided into M > 1 sub-screens along the arrangement direction of the timing-apertures, with adjacent sub-screens emitting light of mutually orthogonal polarization. At a time-point of each time period, a group of M timing-apertures, which correspond to the M sub-screens in a one-by-one manner along the arrangement direction, are turned on for creating an M-fold FOV, with each polarized timing-aperture of the group allowing light from the corresponding sub-screen passing through and blocking light from sub-screen(s) adjacent to the corresponding sub-screen. At 2T > 1 time-points of each time period, 2T groups of timing-apertures are turned on sequentially for presenting more than one two-dimensional images of the displayed scene to each eye, to implement SMV display based on persistence of vision. M stands for the FOV magnification number and T stands for the two-dimensional image number for each eye. As proof, a 3-fold FOV of 41° gets implemented experimentally with a currently available timing-aperture array of M = 3, accompanied by an effective noise-free region (ENFR) of 8.34 mm. Furthermore, the promising of freeing FOV from timing-aperture constraint fundamentally by larger M is described, out-of-screen blur along strip direction of the timing-apertures and the problem of limited ENFR are discussed.

Effect of Dietary Forage/Concentrate Ratio on Nutrient Digestion and Energy and Protein Metabolism in Adult Donkeys.

The domestic donkey is a unique equid species with specific nutritional requirements; however, limited feeding studies have been addressed so far to understand nutrient digestion and metabolism in donkeys. In the present study, six adult female Xinjiang donkeys (180 ± 10 kg live weight) were applied in a 3 × 3 Latin square design to investigate the effect of the forage/concentrate ratio (F/C) in three experimental diets on N and energy balance within 12 weeks. Rice straw and alfalfa hay were chosen as forage ingredients, and the diets included the following: (1) a high-fiber (HF) ration (F/C = 80:20), (2) a medium-fiber (MF) ration (F/C = 55:45), and (3) a low-fiber (LF) ration (35:45). After the fixed amount of diets were daily allowed to the animals, total feces and urine were collected to determine total tract digestibility, N and energy balance. As a result, dry matter intake did not differ among the three diet groups. Decreasing the dietary F/C significantly promoted protein digestibility and decreased fiber digestibility. The N and energy balance analysis showed that increasing the F/C remarkably (p < 0.01) decreased N retention through the increase in N excretion in urine, and the highest N loss relative to N intake was observed in MF. Meanwhile, decreasing the F/C linearly increased the conversion efficiency of digestible energy to metabolizable energy. Taken together, the results obtained in the present study implicated that the dietary forage level should not be less than 55% to maintain greater N and energy utilization in feeding practice, otherwise, a donkey's N utilization might be highly discounted.

Effect of Dietary Forage: Concentrate Ratio on Pre-Caecal and Total Digestive Tract Digestibility of Diverse Feedstuffs in Donkeys as Measured by the Mobile Nylon Bag Technique.

The domestic donkey is a unique equid species with specific nutritional requirements, however, limited laboratory evidences are available to address the digestibility contribution of the prececum in relation to the total digestive tract. In the present study, six caecum-fistulated adult female Xinjiang donkeys served as the experimental animals in a 3 × 3 Latin square design, and mobile nylon bag technique was applied to determine the effect of dietary F:C ratio on pre-caececum and total digestive tract digestibility of rice straw, alfalfa hay, corn meal, and soybean meal. The dietary treatments included: (1) HF, a high-fiber ration (F:C = 80:20), (2) MF, a medium-fiber ration (F:C = 55:45), and (3), LF, a low-fiber ration (F:C = 35:65). The experiment consisted of three consecutive Latin square periods, and each period lasted 25 days. In each period, the animals were administrated naso-gastrically nylon bags (38 µm pore size) containing aforementioned feeds. After 1.5 h intubation, the bags were checked once an hour and collected at the ileo-caecal junction (small intestine bag, D1) and in the feces (fecal bag, D2). Regardless whatever feeds were introduced, the percentage of bag collected (BC) was quadratically (HF) or linearly (MF and LF) increased against different fixed bag collection time. The highest BC occurred in MF (73.8%), but no significant difference was observed between HF (62.3%) and LF (50.8%). The lowest mean bag retention time was observed in HF (2.7 h), and no significant difference occurred between MF (4.6 h) and LF (5.0 h) diets. For each feed, D1 and D2 digestibility for DM, CP, NDF, and ADF did not differ among three dietary treatments (p > 0.05). Regardless of whatever diets were fed to the donkeys, D2 digestibility for DM and CP among the feeds ranked as: soybean meal > corn meal > alfalfa hay > rice straw (p < 0.01). D1 digestibility for DM among the feeds ranked as: corn meal > soybean meal > alfalfa hay > rice straw (p < 0.01). D1 digestibility for CP among the feeds ranked as: soybean meal > corn meal > alfalfa hay > rice straw (p < 0.01). In summary, dietary forage: concentrate ratio did not affect pre-caecal or total tract nutrient digestibility. The fiber level in feeds was the main limiting factor to affect the digestibility contribution of the pre-caecum in relation to the total digestive tract.

Phenotypic Variation and Carbapenem Resistance Potential in OXA-499-Producing Acinetobacter pittii.

Acinetobacter pittii is increasingly recognized as a clinically important species. Here, we identified a carbapenem-non-resistant A. pittii clinical isolate, A1254, harboring bla OXA- 499, bla OXA- 826, and bla ADC- 221. The bla OXA- 499 genetic environment in A1254 was identical to that of another OXA-499-producing, but carbapenem-resistant, A. pittii isolate, YMC2010/8/T346, indicating the existence of phenotypic variation among OXA-499-producing A. pittii strains. Under imipenem-selective pressure, the A1254 isolate developed resistance to carbapenems in 60 generations. Two carbapenem-resistant mutants (CAB009 and CAB010) with mutations in the bla OXA- 499 promoter region were isolated from two independently evolved populations (CAB001 and CAB004). The CAB009 mutant, with a mutation at position -14 (A to G), exhibited a four-fold higher carbapenem minimum inhibitory concentration (MIC) and a 4.53 ± 0.19 log2 fold change higher expression level of bla OXA- 499 than the ancestor strain, A1254. The other mutant, CAB010, with a mutation at position -42 (G to A), showed a two-fold higher carbapenem MIC and a 1.65 ± 0.25 log2 fold change higher bla OXA- 499 expression level than the ancestor strain. The bla OXA- 499 gene and its promoter region were amplified from the wild-type strain and two mutant isolates and then individually cloned into the pYMAb2-Hyg r vector and expressed in Acinetobacter baumannii ATCC 17978, A. pittii LMG 1035, and A. pittii A1254. All the transformed strains were resistant to carbapenem, irrespective of whether they harbored the initial or an evolved promoter sequence, and transformed strains expressing the promoter from the most resistant mutant, CAB009, showed the highest carbapenem MICs, with values of 32-64 µg/ml for imipenem and 128 µg/ml for meropenem. RNA sequencing was performed to confirm the contribution of bla OXA- 499 to the development of carbapenem resistance. Although the CAB009 and CAB010 transcriptional patterns were different, bla OXA- 499 was the only differentially expressed gene shared by the two mutants. Our results indicate that carbapenem-non-resistant Acinetobacter spp. strains carrying bla OXA genes have the potential to develop carbapenem resistance and need to be further investigated and monitored to prevent treatment failure due to the development of resistance.

Capsule Thickness, Not Biofilm Formation, Gives Rise to Mucoid Acinetobacter baumannii Phenotypes That are More Prevalent in Long-Term Infections: A Study of Clinical Isolates from a Hospital in China.

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen of critical importance due to the increasing numbers of antibiotic-resistant isolates. Colonies can have a smooth or matt appearance, but also exhibit slimy, mucoid growth, with the latter being increasingly isolated in patients in recent years. METHODS: We isolated 60 A. baumannii strains from altogether 56 patients and found that all patients were infected by mucoid strains, with four patients having also matt phenotypes in addition to the mucoid ones. The morphology of the colonies and capsules was observed. The antibiotics susceptibilities were tested, and the biofilm formation ability was determined by crystal violet staining. The whole-genome sequencing (WGS) was performed on all the strains, and then the core genome multilocus sequence typing (cgMLST) and drug resistance gene analysis were performed. Finally, a part of isolates were selected to test virulence in a Galleria mellonella model. RESULTS: We observed much larger capsules in the mucoid strains compared to the matt isolates. But the mucoid phenotype did not correlate with the amount of biofilm produced by the strain. Almost all mucus-type A. baumannii were multi-drug resistant isolates, containing various antibiotic resistance genes. The main ST types of mucoid-type A.baumannii were ST191 and ST195, of which ST191 isolates were more virulence, while ST195 isolates were weaker. CONCLUSION: The mucoid A. baumannii had resistance to most antibiotics and some strains had high virulence, which should be paid attention in clinical.

Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives.

To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast cancer cells MCF-7, colon cancer cells HCT-116, as well as leukemia cells K562. Compound 11j displayed the strongest antiproliferative activity with IC50 values of 3.91, 6.90, 4.36 and 1.12 µM against the above four cells, respectively. Nevertheless, it showed an IC50 value >40 µM against human peripheral blood mononuclear cells (PBMCs), which demonstrated high selectivity between normal and cancer blood cells. In further mechanism studies, 11j showed the capability to induce K562 cells apoptosis, S phase cell cycle arrest and mitochondrial membrane potential disorder. Besides, 11j was found to be effective in promoting the expression of proapoptotic protein Bad and suppressing the expression of anti-apoptotic proteins Bcl-xL, catalase, survivin, claspin and clusterin.

GaN-based mid-power flip-chip light-emitting diode with high -3 dB bandwidth for visible light communications.

By directly flip-chip soldering three mid-power light-emitting diode (LED) chips with periodic micro-via-holes on ceramic substrates, -3 dB modulation bandwidths of 49.9 MHz, 58.8 MHz, and 25 MHz are obtained at the driving current of 170 mA. To the best of our knowledge, these are the reported highest -3 dB bandwidth values for flip-chip power-type LEDs (FC-LEDs) at the low-bias current levels. Moreover, good radiant powers are also achieved: 180.2 mW, 168.8 mW, and 233.8 mW at 150 mA, respectively. With a gold wire-free feature, the fabricated FC-LEDs could offer an opportunity to miniaturize the package volume of a LED module for illumination and free-space high-speed VLC dual-usage applications.

Colistin Resistance in Acinetobacter baumannii MDR-ZJ06 Revealed by a Multiomics Approach.

Acinetobacter baumannii has emerged as an important opportunistic pathogen due to its ability to acquire resistance to most currently available antibiotics. Colistin is often considered as the last line of therapy for infections caused by multidrug-resistant A. baumannii (MDRAB). However, colistin-resistant A. baumannii strain has recently been reported. To explore how multiple drug-resistant A. baumannii responded to colistin resistance, we compared the genomic, transcriptional and proteomic profile of A. baumannii MDR-ZJ06 to the induced colistin-resistant strain ZJ06-200P5-1. Genomic analysis showed that lpxC was inactivated by ISAba1 insertion, leading to LPS loss. Transcriptional analysis demonstrated that the colistin-resistant strain regulated its metabolism. Proteomic analysis suggested increased expression of the RND efflux pump system and down-regulation of FabZ and ß-lactamase. These alterations were believed to be response to LPS loss. In summary, the lpxC mutation not only established colistin resistance but also altered global gene expression.

High prevalence of ESBL-producing Escherichia coli and Klebsiella pneumoniae in community-onset bloodstream infections in China.

OBJECTIVES: Community-onset bloodstream infections (COBSIs) caused by ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumoniae (ESBL-KP) are increasing globally. This study aimed to investigate the epidemiology and risk factors of ESBL-EC and ESBL-KP in COBSIs in China. METHODS: A prospective, multicentre study was performed in 28 tertiary hospitals from September 2013 to November 2014. All isolates and ESBLs were microbiologically characterized. A statistical analysis of risk factors was performed using binary logistic regression. The trial was registered with ClinicalTrials.gov (NCT01961206). RESULTS: A total of 919 consecutive episodes of COBSIs were reported and 640 E. coli and 279 K. pneumoniae isolates (non-duplicate) were collected. According to the criteria, 662 (72.0%) cases were classified as having community-acquired bloodstream infections, while the remaining 257 (28.0%) were classified as having healthcare-associated bloodstream infections. The proportions of ESBL producers were 55.5% (355/640) among E. coli isolates and 16.5% (46/279) among K. pneumoniae isolates, respectively. Healthcare-associated infections, obstructive urinary tract disease, previous surgical history and use of a cephalosporin antibiotic within 3 months were independent predictors of COBSIs caused by ESBL-EC. Heart failure was the only independent risk factor for COBSIs due to ESBL-KP. Age was not independently associated with infections caused by ESBL producers. CTX-M-14 was the most common ESBL genotype and was widespread throughout the country. CONCLUSIONS: ESBL producers are highly prevalent in COBSIs in China, especially among cases caused by E. coli. For these resistant pathogens, clinicians should consider adequate empirical therapy, and different risk factors for prediction should be used in this country.

Super multi-view three-dimensional display technique for portable devices.

Portable display devices, such as intelligent telephones and panel PCs, have become parts of modern people's daily life. Their mainstream display interfaces are based on two-dimensional (2D) images. Although some three-dimensional (3D) technologies have been proposed for portable devices, comfortable visual effects are untouched until now. A super multi-view (SMV) system with comfortable 3D effects, constructed by a group of OLED microdisplay/projecting lens pairs, is proposed in this paper. Through gating different segments of each projecting lens sequentially and refreshing the virtual image of the corresponding microdisplay synchronously, the proposed SMV system greatly decreases the demand on the number of employed microdisplays and at the same time takes a thin optical structure, endowing great potential for portable devices.