Transcription factor PbNAC71 regulates xylem and vessel development to control plant height.

Dwarfism is an important agronomic trait in fruit breeding programs. However, the germplasm resources required to generate dwarf pear (Pyrus spp.) varieties are limited. Moreover, the mechanisms underlying dwarfism remain unclear. In this study, "Yunnan" quince (Cydonia oblonga Mill.) had a dwarfing effect on "Zaosu" pear. Additionally, the dwarfism-related NAC transcription factor gene PbNAC71 was isolated from pear trees comprising "Zaosu" (scion) grafted onto "Yunnan" quince (rootstock). Transgenic Nicotiana benthamiana and pear OHF-333 (Pyrus communis) plants overexpressing PbNAC71 exhibited dwarfism, with a substantially smaller xylem and vessel area relative to the wild-type controls. Yeast one-hybrid, dual-luciferase, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays indicated that PbNAC71 downregulates PbWalls are thin 1 expression by binding to NAC-binding elements in its promoter. Yeast two-hybrid assays showed that PbNAC71 interacts with the E3 ubiquitin ligase PbRING finger protein 217 (PbRNF217). Furthermore, PbRNF217 promotes the ubiquitin-mediated degradation of PbNAC71 by the 26S proteasome, thereby regulating plant height as well as xylem and vessel development. Our findings reveal a mechanism underlying pear dwarfism and expand our understanding of the molecular basis of dwarfism in woody plants.

Biobased Tannic Acid-Chitosan Composite Membranes as Reusable Adsorbents for Effective Enrichment of Phosphopeptides.

High-performance reusable materials from renewable resources are rare and urgently required in bioseparation. Herein, a series of tannic acid-chitosan composite membranes for the enrichment of phosphopeptides were fabricated by the freeze casting method. First, a tannic acid-chitosan composite membrane was acquired via the multiple hydrogen bonds between tannic acid and chitosan, which had a long-range aligned three-dimensional microstructure. Second, a covalent-hydrogen bond hybrid composite was also fabricated, with stable and aligned honeycomb-like microstructures that formed by the synergy of covalence and hydrogen bonding. Besides, a ternary composite membrane was "one-pot" synthesized by the copolymerization of tannic acid, chitosan, and Ti4+ ions, indicating the feasibility of involving metal ions in the composition of the polymer skeleton in place of additional modification steps. The as-prepared chitosan composite membranes exhibited excellent performance in the enrichment of phosphopeptides from ß-casein tryptic digest and human serum. Benefitting from the long-range aligned honeycomb-like structure coordinated by hydrogen bonds and covalent bonds, and a large number of pyrogallol functional groups provided by tannic acid, the covalent-hydrogen bond hybrid membrane showed excellent reusability and could be reused up to 16 times in phosphopeptide enrichment, as far as we know, which is the best reported result to date.

Development of a smartphone screening test for preclinical Alzheimer's disease and validation across the dementia continuum.

BACKGROUND: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10-20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. METHODS: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50-92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30-40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50-100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. DISCUSSION: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults.

INTRODUCTION: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. METHODS: 1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests. RESULTS: All single-key (R2 adj  = 8.8%, ΔAIC = 5.2) and alternate-key (R2 adj  = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R2 adj  = 8.1%). No tapping features improved estimation of working memory. DISCUSSION: Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts. HIGHLIGHTS: We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor- and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self-administered test may aid stratification of community cohorts.

The circular RNA circHMGB2 drives immunosuppression and anti-PD-1 resistance in lung adenocarcinomas and squamous cell carcinomas via the miR-181a-5p/CARM1 axis.

BACKGROUND: Previous studies have confirmed the oncogenic role of HMGB2 in various cancers, but the biological functions of HMGB2-derived circRNAs remain unknown. Thus, we intended to investigate the potential role of HMGB2-derived circRNAs in lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). METHODS: The expression profiles of HMGB2-derived circRNAs in LUAD and LUSC tissues and matched normal tissues were assessed using qRT-PCR. The role of circHMGB2 in the progression of the LUAD and LUSC was determined in vitro by Transwell, CCK-8, flow cytometry and immunohistochemistry assays, as well as in vivo in an immunocompetent mouse model and a humanized mouse model. In addition, in vivo circRNA precipitation assays, luciferase reporter assays and RNA pulldown assays were performed to explore the underlying mechanism by which circHMGB2 promotes anti-PD-1 resistance in the LUAD and LUSC. RESULTS: The expression of circHMGB2 (hsa_circ_0071452) was significantly upregulated in NSCLC tissues, and survival analysis identified circHMGB2 as an independent indicator of poor prognosis in the LUAD and LUSC patients. We found that circHMGB2 exerted a mild effect on the proliferation of the LUAD and LUSC cells, but circHMGB2 substantially reshaped the tumor microenvironment by contributing to the exhaustion of antitumor immunity in an immunocompetent mouse model and a humanized mouse model. Mechanistically, circHMGB2 relieves the inhibition of downstream CARM1 by sponging miR-181a-5p, thus inactivating the type 1 interferon response in the LUAD and LUSC. Moreover, we found that the upregulation of circHMGB2 expression decreased the efficacy of anti-PD-1 therapy, and we revealed that the combination of the CARM1 inhibitor EZM2302 and an anti-PD-1 antibody exerted promising synergistic effects in a preclinical model. CONCLUSION: circHMGB2 overexpression promotes the LUAD and LUSC progression mainly by reshaping the tumor microenvironment and regulating anti-PD-1 resistance in the LUAD and LUSC patients. This study provides a new strategy for the LUAD and LUSC treatment.

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer's disease and estimate 5-year risks of cognitive decline and dementia.

BACKGROUND: The worldwide prevalence of dementia is rapidly rising. Alzheimer's disease (AD), accounts for 70% of cases and has a 10-20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust 'self-testing' data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. METHODS: Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. DISCUSSION: This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.

Applications of artificial intelligence to aid early detection of dementia: A scoping review on current capabilities and future directions.

BACKGROUND & OBJECTIVE: With populations aging, the number of people with dementia worldwide is expected to triple to 152 million by 2050. Seventy percent of cases are due to Alzheimer's disease (AD) pathology and there is a 10-20 year 'pre-clinical' period before significant cognitive decline occurs. We urgently need, cost effective, objective biomarkers to detect AD, and other dementias, at an early stage. Risk factor modification could prevent 40% of cases and drug trials would have greater chances of success if participants are recruited at an earlier stage. Currently, detection of dementia is largely by pen and paper cognitive tests but these are time consuming and insensitive to the pre-clinical phase. Specialist brain scans and body fluid biomarkers can detect the earliest stages of dementia but are too invasive or expensive for widespread use. With the advancement of technology, Artificial Intelligence (AI) shows promising results in assisting with detection of early-stage dementia. This scoping review aims to summarise the current capabilities of AI-aided digital biomarkers to aid in early detection of dementia, and also discusses potential future research directions. METHODS & MATERIALS: In this scoping review, we used PubMed and IEEE Xplore to identify relevant papers. The resulting records were further filtered to retrieve articles published within five years and written in English. Duplicates were removed, titles and abstracts were screened and full texts were reviewed. RESULTS: After an initial yield of 1,463 records, 1,444 records were screened after removal of duplication. A further 771 records were excluded after screening titles and abstracts, and 496 were excluded after full text review. The final yield was 177 studies. Records were grouped into different artificial intelligence based tests: (a) computerized cognitive tests (b) movement tests (c) speech, conversion, and language tests and (d) computer-assisted interpretation of brain scans. CONCLUSIONS: In general, AI techniques enhance the performance of dementia screening tests because more features can be retrieved from a single test, there are less errors due to subjective judgements and AI shifts the automation of dementia screening to a higher level. Compared with traditional cognitive tests, AI-based computerized cognitive tests improve the discrimination sensitivity by around 4% and specificity by around 3%. In terms of speech, conversation and language tests, combining both acoustic features and linguistic features achieve the best result with accuracy around 94%. Deep learning techniques applied in brain scan analysis achieves around 92% accuracy. Movement tests and setting smart environments to capture daily life behaviours are two potential future directions that may help discriminate dementia from normal aging. AI-based smart environments and multi-modal tests are promising future directions to improve detection of dementia in the earliest stages.

New horizons in late-onset essential tremor: a pre-cognitive biomarker of dementia?

Essential tremor (ET) is the most common cause of tremor in older adults. However, it is increasingly recognised that 30-50% of ET cases are misdiagnosed. Late-onset ET, when tremor begins after the age of 60, is particularly likely to be misdiagnosed and there is mounting evidence that it may be a distinct clinical entity, perhaps better termed 'ageing-related tremor'. Compared with older adults with early-onset ET, late-onset ET is associated with weak grip strength, cognitive decline, dementia and mortality. This raises questions around whether late-onset ET is a pre-cognitive biomarker of dementia and whether modification of dementia risk factors may be particularly important in this group. On the other hand, it is possible that the clinical manifestations of late-onset ET simply reflect markers of healthy ageing, or frailty, superimposed on typical ET. These issues are important to clarify, especially in the era of specialist neurosurgical treatments for ET being increasingly offered to older adults, and these may not be suitable in people at high risk of cognitive decline. There is a pressing need for clinicians to understand late-onset ET, but this is challenging when there are so few publications specifically focussed on this subject and no specific features to guide prognosis. More rigorous clinical follow-up and precise phenotyping of the clinical manifestations of late-onset ET using accessible computer technologies may help us delineate whether late-onset ET is a separate clinical entity and aid prognostication.

Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC.

BACKGROUND: CD8+ T cells play a critical role in the innate antitumour immune response. Recently, CD8+ T cell dysfunction has been verified in various malignant cancers, including non-small cell lung cancer (NSCLC). However, the molecular biological mechanisms of CD8+ T cell dysfunction in human NSCLC are still unclear. METHODS: The expression of circular ubiquitin-specific protease-7 (circUSP7) in NSCLC tissues, exosomes, and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were isolated from the culture medium of NSCLC cells and the plasma of NSCLC patients using an ultracentrifugation method and the ExoQuick Exosome Precipitation Solution kit. The exosomes were then characterized by transmission electronic microscopy (TEM), NanoSight and western blotting. The role of circUSP7 in CD8+ T cell dysfunction was assessed by enzyme-linked immunosorbent assay (ELISA). In vivo circular RNA (circRNA) precipitation (circRIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were performed to explore the molecular mechanisms of circUSP7 in CD8+ T cells. In a retrospective study, the clinical characteristics and prognostic significance of circUSP7 in NSCLC tissues were determined. RESULTS: The expression levels of circUSP7 were higher in human NSCLC tissues than in matched adjacent nontumour tissues. Increased levels of circUSP7 indicate poor clinical prognosis and CD8+ T cell dysfunction in patients with NSCLC. The circUSP7 found in NSCLC patient plasma is predominantly secreted by NSCLC cells in an exosomal manner, and circUSP7 inhibits IFN-γ, TNF-α, Granzyme-B and Perforin secretion by CD8+ T cells. Furthermore, circUSP7 inhibits CD8+ T cell function by upregulating the expression of Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) via sponging miR-934. Finally, we show that circUSP7 may promote resistance to anti-PD1 immunotherapy in NSCLC patients. CONCLUSIONS: Exosomal circUSP7 is predominantly secreted by NSCLC cells and contributes to immunosuppression by promoting CD8+ T cell dysfunction in NSCLC. CircUSP7 induces resistance to anti-PD1 immunotherapy, providing a potential therapeutic strategy for NSCLC patients.

ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation.

BACKGROUND: Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. METHODS: Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. RESULTS: We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. CONCLUSION: Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.

Synthesis of fully porous silica microspheres with high specific surface area for fast HPLC separation of intact proteins and digests of ovalbumin.

Fully porous silica microspheres (FPSM) with high specific surface area and hierarchical pore as matrix for HPLC were prepared. First, the porous silica nanospheres with controllable particle size and pore diameter were successfully synthesized using a dual-templating approach, the pore size of nanospheres can be increased to 18.4 nm by changing the molar ratios of octyltrimethylammonium bromide (TOMAB) and cetyltrimethyl ammonium bromide (CTAB), which is suitable for separation and analysis of biomolecules without pore enlargement. Then, the micron FPSM with hierarchical pore were synthesized by polymerization-induced colloid aggregation (PICA) using the porous nanospheres as a silicon source, which has a large mesoporous structure (35.2 nm) and high specific surface area (560 m2 g-1). Subsequently, the FPSM modified with octadecyltrichlorosilane were studied as stationary phase for separation of cytochrome C, lysozyme, ribonuclease A, and ovalbumin, bovine serum albumin, and the baseline separation of five proteins was achieved within 1 min. The prepared column was also applied to the fast separation of digests of ovalbumin, and more chromatographic peaks were obtained compared to a commercial column under the same gradient elution conditions. In addition, the static-binding capacity of the functionalized FPSM for bovine serum albumin (BSA) was measured to be 276 mg g-1, which was nearly twice the static adsorption given in literature. Therefore, these FPSM with high specific surface area and hierarchical pore structure are expected to have great potential for the separation of complex biological samples using HPLC. Graphical abstract A synthetic strategy was provided towards FPSM with hierarchical pores and high specific surface area using porous nanospheres as silicon source. The outstanding performance of the FPSM is that it has a high specific surface area while maintaining a large mesoporous size, which overcomes the disadvantage of sacrificing the specific surface area when increasing the pore size of porous silica microspheres prepared by using the traditional PICA method.

Modified Distal Aortic Arch Occlusion During Aortic Arch Replacement.

BACKGROUND: Circulatory arrest has been identified as an independent risk factor related to postoperative mortality in patients with Stanford type A aortic dissection. This study described a modified technique for distal aortic arch occlusion that markedly shortened the circulatory arrest time. The early results are encouraging. METHODS: From May 2016 to September 2018, 51 patients with Stanford type A aortic dissection underwent the modified procedure for aortic arch replacement. All operations were performed via transitory circulatory arrest by clamping the distal aorta between the left common carotid artery and the left subclavian artery. The in-hospital and follow-up data of the treated patients were investigated. RESULTS: Successful repair of the involved vasculature was achieved in all patients. One (1) patient died due to postoperative aspiration and infection, and three patients required continuous renal replacement therapy due to poor preoperative renal function. The remaining patients were successfully discharged. The median average circulatory arrest time was 5.0 (3.0-6.0) minutes. No cases of tracheotomy, delayed closure, secondary thoracotomy, or other complications occurred. During the follow-up period of 2.4-18.6 months, the implanted grafts and stented elephant trunks were all fully open and not kinked. CONCLUSIONS: A modified distal aortic arch occlusion can considerably shorten the duration of circulatory arrest. Current experience suggests that this approach can serve as a feasible alternative for patients during aortic arch replacement because of its simplicity and satisfactory clinical effects.

CircRNA fibroblast growth factor receptor 3 promotes tumor progression in non-small cell lung cancer by regulating Galectin-1-AKT/ERK1/2 signaling.

The dysregulation of circular RNA (circRNA) expression is involved in the progression of several cancers, including non-small cell lung cancer (NSCLC). However, the role and underlying molecular mechanisms of circRNA FGFR3 (circFGFR3) in NSCLC progression remains unknown. Here, we used quantitative real-time polymerase chain reaction to validate that circFGFR3 expression was higher in NSCLC tissues than in the paratumor tissues. Furthermore, our study indicated that the forced circFGFR3 expression promoted NSCLC cell invasion and proliferation. Mechanistically, we found that circFGFR3 promoted NSCLC cell invasion and proliferation via competitively combining with miR-22-3p to facilitate the galectin-1 (Gal-1), p-AKT, and p-ERK1/2 expressions. Clinically, we revealed that the high circFGFR3 expression correlates with the poor clinical outcomes in patients with NSCLC. Together, these data provide mechanistic insights into the circFGFR3-mediated regulation of both the AKT and ERK1/2 signaling pathways by sponging miR-22-3p and increasing Gal-1 expression.

Effects of fat-to-sugar ratio in excess dietary energy on lipid abnormalities: a 7-month prospective feeding study in adult cynomolgus monkeys.

BACKGROUND: Excess energy intake contributes to metabolic disorders. However, the relationship between excess sugar and fat in their contributions to metabolic abnormalities remains to be further elucidated. Here we conducted a prospective feeding experiment to evaluate effects of dietary fat-to-sugar ratio on diet-induced metabolic abnormalities in adult cynomolgus monkeys. METHODS: Four groups of adult cynomolgus monkeys were fed regular chow plus emulsion with combinations of high sugar (HS) or low sugar (HS) and low fat (LF) or high fat (HF) for 7 months. Plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG) and blood glucose were measured for all the four groups of animals during the experiment. RESULTS: Plasma levels of TC and LDL-C gradually increased in all 4 diets groups, with the highest increase found in the LSHF group compared to the other three groups (P = 0.0018 and P = 0.0005 respectively). HF induced increased fasting glucose (P = 0.0077) and HS induced higher TG (P = 0.0227) respectively. Intriguingly, HSHF led to dramatically smaller magnitude of increase in LDL-C and TC levels compared to LSHF, while such difference was absent between the LSLF and LSHF groups. Our findings thus indicate interactive effects of HS and HF on TC and LDL-C. In addition, HF exhibited stronger effects on lipid abnormalities than HS. CONCLUSIONS: In the current study, our prospective feeding experiment in adult cynomolgus monkeys revealed effects of different fat-to-sugar ratios on diet-induced metabolic abnormalities. Furthermore, our findings suggest that not only excess dietary energy but also the balance of dietary fat-to-sugar ratio matters in diet-induced lipid abnormalities.

One-pot synthesis of SiO2@SiO2 core-shell microspheres with controllable mesopore size as a new stationary phase for fast HPLC separation of alkyl benzenes and ß-agonists.

Monodisperse SiO2@SiO2 core-shell silica microspheres (CSSM) with enlarged mesopores perpendicular to the particles surface were prepared using a dual-templating approach. With cetyltrimethyl ammonium bromide as the template and octyltrimethyl ammonium bromide as an auxiliary chemical, the pore size can be enlarged from 2.6 to 10.6 nm. The average shell thickness can be increased from 31 nm to 97 nm by adjusting the concentrations of the surfactants under continuous addition of tetraethyl orthosilicate. After coating twice, the resulting CSSM has a uniform mesoporous shell of about 198 nm thickness and a narrow pore size distribution. The CSSM were then modified with octadecyltrichlorosilane to give a material referred to as CS-C18. It was evaluated by separating the mixture of methylbenzene (toluene), ethylbenzene, n-propylbenzene, n-butylbenzene, n-amylbenzene and hexylbenzene. The baseline separation of the six alkyl benzenes is achieved within 2 min. Compared to a commercial column of type BEH-C18, CS-C18 shows a faster and better separation even at lower back pressure. It was also applied to the fast separation of benzo[a]pyrene, salbutamol, ractopamine and clenbuterolin residues in pork samples. The high column efficiency and better reproducibility suggest that the CSSM can be used as a matrix for fast separation and analysis of several kinds of small analytes. Graphical abstract A dual-templating approach was utilized to produce the core shell microsphere with controllable mesopore channels by using hexadecyltrimethylammonium bromide (CTAB) as the template and trioctylmethylammonium bromide (TOMAB) as an auxiliary chemical to enlarge the size of CTAB micelles.

Polymeric ionic liquid-assembled graphene-immobilized silica composite for selective isolation of human serum albumin from human whole blood.

Polymeric ionic liquids (PILs) with 1-vinyl-3-ethylimidazolium cations and two different anions of Br- and PF6- were assembled onto the surface of graphene (G) nanosheets. The derived two composites, i.e., PIL(Br)-G and PIL(PF6)-G, were further efficiently immobilized onto the surface of silica nanoparticles via self-assembly technique. The obtained two PIL-G/SiO2 nanocomposites exhibited diverse adsorption performances toward proteins through adjusting the anions of PILs. Electrostatic attractions between proteins and the nanocomposites dominated protein adsorption, while the presence of PF6- anions weakened electrostatic interactions and deteriorated the selective adsorption of target protein, i.e., bovine serum albumin (BSA) in this case. Specifically, PIL(Br)-G/SiO2 nanocomposite displayed high selectivity toward BSA and a high adsorption efficiency of ca. 98% was achieved for 100 mg L-1 BSA in a Britton-Robinson (B-R) buffer at pH 5. HPLC analysis demonstrated the selectivity of PIL(Br)-G/SiO2 nanocomposite toward BSA in the presence of abundant hemoglobin and cytochrome c. The practical applicability was verified by performing selective isolation of human serum albumin (HSA) from human whole blood. Graphical abstract Selective isolation of human serum albumin from blood by polymeric ionic liquid assembled graphene immobilized silica nanocomposite with tunable anions.

Tunable composites prepared from graphene oxide and zeolitic imidazolate framework-8 for improved selective isolation of hemoglobin.

The authors report on the preparation of composites made from graphene oxide (GO) and zeolitic imidazolate framework-8 (ZIF-GO), with various fractions of GO. GO acts as the template and as a modulator for the surface properties of the composites. It also improves the selective adsorption of specific proteins, i.e. hemoglobin (Hb) in this case. The adsorption capacity for Hb is as high as 436 mg g-1 when using a composite containing 20% of GO as sorbent, and 95% of specific activity is maintained for the Hb recovered. The sorbent is applied to selectively isolate Hb from human whole blood. Graphical abstract Graphene oxide-zeolitic imidazolate framework-8 composites (ZIF-GO) with varying mass ratios of GO were prepared in order to tune surface properties and to improve the adsorption selectivity toward hemoglobin.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.

Rapid Detection of Serratia fonticola by TaqMan Quantitative Real-Time PCR Using Primers Targeting the gyrB Gene.

A gyrB gene is present in the majority of bacterial species, and encodes the ATPase domain of DNA gyraseB-subunit protein, which is essential for transcription and replication of bacteria. The gyrB gene exhibits higher nucleotide sequence variability than the 16S rDNA gene and thus could be more reliable in differentiating Serratia fonticola. A species-specific primer pair and probe were designed for quantitative real-time PCR detection of S. fonticola using gyrB as the target gene. Nine members of the Serratia family (representing nine Serratia species) were chosen to verify the specificity of the primers. Additionally, two species each of Salmonella and Klebsiella, and five other species belonging to five other genera of Enterobacteriaceae, were tested for primer cross-reaction. All the tested strains gave negative results. The limit of detection for S. fonticola using the gyrB gene was 100 copies per PCR reaction. This TaqMan PCR assay provided a specific, rapid, and sensitive method to detect S. fonticola based on its gyrB gene.

Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling.

Pancreatic adenocarcinoma (PDAC) is known to have a poor prognosis partly because of lack of effective biomarkers. In the test set, we investigated dysbindin (DTNBP1) as a potential biomarker for PDAC by comparing preoperative and postoperative serum mass spectrometry (MS) proteomic profilings. Of the included 50 PDAC patients, 42 (positivity of 84.0%) detected a lower MS peak in postoperative serums than preoperative ones which was then identified as dysbindin. In the verification set, receiver operating characteristics (ROC) were used to assess diagnostic efficiency. 550 participants were included in the verification set [250 with PDAC, 80 with benign biliary obstruction (BBO), 70 with chronic pancreatitis (CP) and 150 healthy donors (HD)]. Dysbindin was increased in PDAC patient sera than in all controls. ROC curves revealed the optimum diagnostic cutoff for dysbindin was 699.16 pg/ml [area under curve (AUC) 0.849 (95% CI 0.812-0.885), sensitivity 81.9% and specificity 84.7%]. Raised concentration of dysbindin in sera could differentiate PDAC from BBO, CP and HD. Moreover, dysbindin maintained its diagnostic accuracy for PDAC patients who were CA19-9 negative [AUC 0.875 (95% CI 0.804-0.945), sensitivity 83.0%, specificity 89.0%] and for patients with benign biliary obstruction [AUC 0.849 (95% CI 0.803-0.894), sensitivity 82.3%, specificity 84.0%].Our discovery of dysbindin may complement measurement of CA19-9 in the diagnosis of PDAC and help to discriminate PDAC from other pancreatic diseases or begin biliary obstruction.