bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallacycle/Metallacage‐Cored Fluorescent Supramolecular Assemblies with Aggregation‐Induced Emission Properties
Authors: Li Yang , Zhang Jinjin , Li Hui , Fan Yiqi , He Tian , Qiu Huayu , Yin Shouchun
Published: March 2020

Fluorescent supramolecular assemblies have attracted significant attention for their application as bioimaging agents, biological and chemical sensors, light‐emitting materials, and gene and drug vectors. The introduction of supramolecular coordination complexes constructed by the spontaneous formation of dative metal–ligand bonds through coordination‐driven self‐assembly into fluorescent supramolecular assemblies is of particular interest. This is because the introduction of metal coordination renders the synthesized assemblies excellent stability in addition to providing unique emissions that are different from the fluorescent ligands or metal ions. The discovery of aggregation‐induced emission (AIE), wherein the fluorophores are nonfluorescent in the molecular state, but become highly emissive in the aggregate state, presents new chances for fluorescent supramolecular assemblies since such assemblies are often required to be employed at high concentrations or in the solid state. This progress report provides a summary of the recent design, construction, and application of metallacycle/metallacage‐cored fluorescent supramolecular assemblies based on coordination‐driven self‐assembly, wherein the assemblies exhibit AIE properties. Example applications discussed in detail include light‐emitting materials, chemical and biological sensors, bioimaging agents, and cancer therapy. Moreover, several unsolved issues related to metallacycle/metallacage‐cored fluorescent supramolecular assemblies are discussed in the context of possible future applications of this field.
Enantioselective Copper‐Catalyzed Radical Ring‐Opening Cyanation of Cyclopropanols and Cyclopropanone Acetals
Authors: Wu Lianqian , Wang Lei , Chen Pinghong , Guo Yin‐Long , Liu Guosheng
Published: March 2020

A novel approach for enantioselective cyanation of cyclopropanols and their derivatives through copper‐catalyzed radical relay processes has been developed. Various cyclopropanols and cyclopropanone acetals are compatible to the catalytic conditions, providing β‐carbonyl nitriles with excellent enantioselectivity. These products can be readily converted to chiral γ‐amino acids derivatives and drugs such as (R)‐baclofen. Preliminary mechanistic studies have supported a ring‐opening process for cyclopropanoxy radicals followed by copper‐catalyzed enantioselective cyanation of benzylic radicals to form the C−CN bonds in an enantioselective manner.

magnified image
Adhesive Nanocomposite for Prolonging Foliar Retention and Synergistic Weeding and Nourishing
Authors: Ji Yanzheng , Huang Mengjie , Yan Jia , Qi Taomei , Li Tao , Liu Yanhui , Lü Shaoyu , Liu Mingzhu
Published: March 2020

The volatilization and leaching for most fertilizers and pesticides raise questions about the sustainability of ecosystems. To enhance the utilization of fertilizers and pesticides, pesticide–fertilizer combined nanocomposites are developed to prolong foliar retention and play a synergistic effect of weeding and nourishing for plant growth. The pesticide–fertilizer combined nanocomposites are prepared based on positive‐charge functionalized mesoporous silica and polydopamine, by chelating micronutrients (Zn2+) and loading pesticide 2,4‐D. A high loading capacity of Zn2+ (233.4 mg g−1) and 2,4‐D (17.8%) is achieved. Zn2+ and the pesticide show excellent pH‐responsive release behavior. At pH 7.0, the cumulative release is 45.35% for the pesticide after 144 h and 17% for Zn2+ after 30 days. These results reveal that the pesticide–fertilizer combined nanocomposites can remove weeds quickly and provide nutrients for crop growth in the long term. The germination rate of purslane dramatically decreases when treating with the nanocomposites, while that of corn seeds is not influenced. Excellent adhesion performance of the nanocomposites is observed on a hydrophobic surface, which can effectively reduce the risk of being washed away by rain. All the results indicate that the pesticide–fertilizer combined nanocomposites with a good synergistic effect is environmentally friendly for large‐scale application in sustainable modern agriculture.
Emerging Materials and Strategies for Personal Thermal Management
Authors: Hu Run , Liu Yida , Shin Sunmi , Huang Shiyao , Ren Xuecheng , Shu Weicheng , Cheng Jingjing , Tao Guangming , Xu Weilin , Chen Renkun , Luo Xiaobing
Published: March 2020

In this decade, the demands of energy saving and diverse personal thermoregulation requirements along with the emergence of wearable electronics and smart textiles give rise to the resurgence of personal thermal management (PTM) technologies. PTM, including personal cooling, heating, insulation, and thermoregulation, are far more flexible and extensive than the traditional air/liquid cooling garments for the human body. Concomitantly, many new advanced materials and strategies have emerged in this decade, promoting the thermoregulation performance and the wearing comfort of PTM simultaneously. In this review, an overview is presented of the state‐of‐the‐art and the prospects in this burgeoning field. The emerging materials and strategies of PTM are introduced, and classed by their thermal functions. The concept of infrared‐transparent visible‐opaque fabric (ITVOF) is first highlighted, as it triggers the work on advanced PTM by combining it with radiative cooling, and the corresponding implementations and realizations are subsequently introduced, followed by wearable heaters, flexible thermoelectric devices, and sweat‐management Janus textiles. Finally, critical considerations on the challenges and opportunities of PTM are presented and future directions are identified, including thermally conductive polymers and fibers, physiological/psychological statistical analysis, and smart PTM strategies.
Migration and agglomeration of adhesive microparticle suspensions in a pressure‐driven duct flow
Authors: Liu Wenwei , Wu Chuan‐Yu
Published: March 2020

Transport of suspensions consisting of monodisperse adhesive microparticles in a pressure‐driven duct flow with the Reynolds number in the range of 5.4–108 is analyzed by means of a coupled lattice Boltzmann method with the discrete element method. The influence of the adhesion on migration and agglomeration of particles is investigated. The results show that the suspensions undergo a transition from purely lateral focusing to completely agglomeration as the surface energy is increased. A dimensionless adhesion number, defined as the ratio of the adhesive force to the drag force, is employed to characterize the degree of agglomeration. It is found that all the particles come into agglomerates as the adhesion number reaches a critical value. Moreover, a detailed examination of size evolution and velocity illustrates that the agglomerates mainly grow spherically, and their velocities depend on the lateral positions rather than their sizes, as the Stokes number is far below one.
Outcome and determinants of failure to complete primary R‐CHOP treatment for reasons other than non‐response among patients with diffuse large B‐cell lymphoma
Authors: Wästerlid Tove , Harrysson Sara , Andersson Therese M.‐L. , Ekberg Sara , Enblad Gunilla , Andersson Per‐Ola , Jerkeman Mats , Eloranta Sandra , Smedby Karin E.
Published: March 2020

Patients with diffuse large B‐cell lymphoma (DLBCL) who fail to complete planned treatment with R‐CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R‐CHOP for reasons unrelated to non‐response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R‐CHOP were identified through the Swedish lymphoma register 2007‐2014. Of these, 147 (5%) stopped prematurely after 1‐3 cycles of R‐CHOP for reasons unrelated to non‐response, 168 (5%) after 4‐5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non‐response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index ≥1 were significantly associated with failure to complete planned R‐CHOP treatment for other reasons than non‐response. Non‐completion of treatment strongly correlated with survival. Five‐year overall survival for patients who received 1‐3 cycles was 26% (95% CI: 19%‐33%), 49% (95% CI: 41%‐57%) for 4‐5 cycles and 76% (74%‐77%) for patients who completed treatment. Failure to complete planned R‐CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion.
Chinese herb feed additives improved the growth performance, meat quality, and nutrient digestibility parameters of pigs
Authors: Lin Zhong‐ning , Ye Li , Li Zhen‐wu , Huang Xiu‐sheng , Lu Zheng , Yang You‐quan , Xing Huan‐wei , Bai Jie‐ying , Ying Zhao‐yang
Published: March 2020

Background

Since the use of antibiotics in animal feed has become a critical concern worldwide due to severe threats to human health and environment, we are in need of finding alternatives to antibiotics in pig breeding, maintaining the health of pigs, and getting high‐quality pork. As traditional Chinese herbs (TCH) are rich natural resources in China and show great benefits to human health we propose to transfer this abundant resource into animal production industry as additives.

Methods

Three groups of Chinese herbs (groups A, B, and C) were used as feed additives in the diet for pigs. In total 32 pigs were arranged in four groups (groups A, B, C, and control group, NC), fed in the same facility, eight pigs (one group) in each colony, free drinking, for 120 days. The feed:gain ratio (F/G), meat quality, total protein, and amino acid concentration of muscle were checked in the experiments.

Results

After 120 days of feeding, the feed:gain ratio (F/G) of pigs in groups A, B, and C was decreased 17.56%, 9.31%, and 13.86% compared with NC treatment, respectively. The diets supplemented with Chinese herbs improved meat quality, increased loin eye area (especially group A and C showed significant difference, P < .001), the total protein (increased ratio vs NC was A = 4.54%, B = 0.38% and C = 3.53%), amino acid concentration of muscle, increased the villus height:crypt depth ratio, and induced positive effects on serum biochemical parameters and immune function (serum TC and TG concentrations were significantly lower than those in the NC group, P < .05.).

Conclusions

The use of Chinese herbal feed additives can reduce the cost of pig breeding and produce high‐quality pock. The combination of these effects would contribute to better absorption ability of the intestinal tract and yield a better growth performance.
Reevaluation for prognostic value of prognostic burn index in severe burn patients
Authors: Kaita Yasuhiko , Tarui Takehiko , Tanaka Yuya , Suzuki Jun , Yoshikawa Kei , Yamaguchi Yoshihiro
Published: March 2020

Aim

The prognostic burn index (PBI), which consists of half partial‐thickness burn surface area plus full‐thickness burn surface area and age, has been widely used to predict mortality in Japan. However, the prognostic value of PBI has not been investigated sufficiently. The purpose of the present study is to clinically reevaluate the PBI in severe burn patients.

Methods

Data of 69 severe burn patients admitted to the burn center at Kyorin University Hospital (Tokyo, Japan) from January 2008 to December 2017 were analyzed retrospectively. The primary outcome in this study was in‐hospital mortality.

Results

The overall in‐hospital mortality rate was 34.8%. There were significant differences in age, the presence of inhalation injury, total burned surface area, full‐thickness burn area, burn index, and PBI between survivors and non‐survivors. In logistic regression analysis, PBI was independently associated with mortality, while the presence of inhalation injury was not. A PBI above the threshold of 105 was significantly associated with in‐hospital mortality. The area under the receiver operating characteristic curve for PBI was 0.85 (95% confidence interval, 0.73–0.93).

Conclusion

The PBI could be a good prognostic indicator. A PBI above the threshold of 105 was associated with mortality among severe burn patients treated in burn‐care facilities.
Die “grüne” elektrochemische Synthese von Periodat
Authors: Arndt Sebastian , Weis Dominik , Donsbach Kai , Waldvogel Siegfried R.
Published: March 2020

Hochreines Periodat ist relativ teuer, wird jedoch für viele anspruchsvolle Anwendungen, wie zur Synthese von Pharmawirkstoffen (API) benötigt. Die hohen Kosten entstehen durch die Verwendung von Bleidioxid‐Anoden und durch den Einsatz von teuren Edukten in den zurzeit verfügbaren elektrochemischen Herstellungsmethoden. Eine direkte und kosteneffiziente elektrochemische Synthese von Periodat aus Iodid als kostengünstiges und leicht verfügbares Edukt wird berichtet. Die Oxidation wird an bordotierten Diamantanoden durchgeführt, die beständig, metallfrei und ungiftig sind. Die Vermeidung von Bleidioxid reduziert letztendlich die Kosten für die Aufreinigung sowie die Qualitätssicherung. Der elektrolytische Prozess wurde in statistischen Versuchsreihen optimiert und in einer elektrochemischen Flusszelle skaliert. Die Raumzeitausbeute konnte durch mehrfaches Durchpumpen erhöht werden. Eine LC‐PDA‐Analysemethode wurde etabliert, die eine einfache und simultane Quantifizierung von Iodid, Iodat und Periodat in hoher Präzision erlaubt.
Synergistic effects of magnesium oxysulte whisker and multiwalled carbon nanotube on flame retardancy, smoke suppression, and thermal properties of polypropylene
Authors: Dang Li , Tang Delin , Du Xinliu , Zhao Yuntian , Lv Zhihui , Zhu Donghai , Cui Xiangmei
Published: March 2020

In this work, multiwalled carbon nanotube (MWCNT)‐modified magnesium oxysulfate whisker (MOSw) (MOSw‐MWCNT) is successfully synthesized via a facial hydrothermal method. MWCNT is bonded on the surface of MOSw via a bidentate bridging mode of the carboxylate ligation without changing their crystal structures. Then MOSw‐MWCNT is incorporated into polypropylene (PP) matrix to prepare series of PP/MOSw‐MWCNT composites via melt blending. Cone calorimetry test, horizontal and vertical test, and limit oxygen index (LOI) results all show a significant synergistic effect of MOSw and MWCNT on flame‐retardant PP. PP/7MOSw‐3MWCNT composite exhibits the lowest peak heat release rate, total heat release, peak smoke production rate, total smoke production, and burning speed of 332.3 kW/m2, 87.4 MJ/m2, 0.0212 m2/s, 47.7 m2and 23.2 mm/min, respectively. The LOI value of PP/7MOSw‐3MWCNT composite is increased to 23.1% from 18.0% of neat PP. The scanning electron microscopy and Raman spectra of residue char indicate that the degree of graphitization and compactness of the residue char are increased with the amount of MWCNT. The introduction of MOSw and MWCNT both improves the thermal stability of PP matrix, but the excess MWCNT leads to the decomposition of the unstable residue char since its excellent thermal conductivity.
Recombinant Adenosine Deaminase Ameliorates Inflammation, Vascular Disease, and Fibrosis in Preclinical Models of Systemic Sclerosis
Authors: Zhang Yun , Zhu Honglin , Layritz Florian , Luo Hui , Wohlfahrt Thomas , Chen Chih‐Wei , Soare Alina , Bergmann Christina , Ramming Andreas , Groeber Florian , Reuter Christian , Fornasini GianFranco , Soukhareva Nadejda , Schreiber Brian , Ramamurthy Santosh , Amann Kerstin , Schett Georg , Distler Jörg H. W.
Published: March 2020

Objective

Systemic sclerosis (SSc) is characterized by fibrosis, vascular disease, and inflammation. Adenosine signaling plays a central role in fibroblast activation. We undertook this study to evaluate the therapeutic effects of adenosine depletion with PEGylated adenosine deaminase (PEG‐ADA) in preclinical models of SSc.

Methods

The effects of PEG‐ADA on inflammation, vascular remodeling, and tissue fibrosis were analyzed in Fra‐2 mice and in a B10.D2→BALB/c (H‐2d) model of sclerodermatous chronic graft‐versus‐host disease (GVHD). The effects of PEG‐ADA were confirmed in vitro in a human full‐thickness skin model.

Results

PEG‐ADA effectively inhibited myofibroblast differentiation and reduced pulmonary fibrosis by 34.3% (with decreased collagen expression) (P = 0.0079; n = 6), dermal fibrosis by 51.8% (P = 0.0006; n = 6), and intestinal fibrosis by 17.7% (P = 0.0228; n = 6) in Fra‐2 mice. Antifibrotic effects of PEG‐ADA were also demonstrated in sclerodermatous chronic GVHD (reduced by 38.4%) (P = 0.0063; n = 8), and in a human full‐thickness skin model. PEG‐ADA treatment decreased inflammation and corrected the M2/Th2/group 2 innate lymphoid cell 2 bias. Moreover, PEG‐ADA inhibited proliferation of pulmonary vascular smooth muscle cells (reduced by 40.5%) (P < 0.0001; n = 6), and prevented thickening of the vessel walls (reduced by 39.6%) (P = 0.0028; n = 6) and occlusions of pulmonary arteries (reduced by 63.9%) (P = 0.0147; n = 6). Treatment with PEG‐ADA inhibited apoptosis of microvascular endothelial cells (reduced by 65.4%) (P = 0.0001; n = 6) and blunted the capillary rarefication (reduced by 32.5%) (P = 0.0199; n = 6). RNA sequencing demonstrated that treatment with PEG‐ADA normalized multiple pathways related to fibrosis, vasculopathy, and inflammation in Fra‐2 mice.

Conclusion

Treatment with PEG‐ADA ameliorates the 3 cardinal features of SSc in pharmacologically relevant and well‐tolerated doses. These findings may have direct translational implications, as PEG‐ADA has already been approved by the Food and Drug Administration for the treatment of patients with ADA‐deficient severe combined immunodeficiency disease.
Salivary Gland Mucosa‐Associated Lymphoid Tissue–Type Lymphoma From Sjögren’s Syndrome Patients in the Majority Express Rheumatoid Factors Affinity‐Selected for IgG
Authors: Bende Richard J. , Janssen Jerry , Beentjes Anna , Wormhoudt Thera A. M. , Wagner Koen , Haacke Erlin A. , Kroese Frans G. M. , Guikema Jeroen E. J. , van Noesel Carel J. M.
Published: March 2020

Objective

Patients with Sjӧgren's syndrome (SS) have an increased risk of developing malignant B cell lymphomas, particularly mucosa‐associated lymphoid tissue (MALT)–type lymphomas. We have previously shown that a predominant proportion of patients with SS‐associated salivary gland MALT lymphoma express somatically hypermutated IgM with strong amino acid sequence homology with stereotypic rheumatoid factors (RFs). The present study was undertaken in a larger cohort of patients with SS‐associated MALT lymphoma to more firmly assess the frequency of RF reactivity and the significance of somatic IGV‐region mutations for RF reactivity.

Methods

B cell antigen receptors (BCRs) of 16 patients with SS‐associated salivary gland MALT lymphoma were analyzed. Soluble recombinant IgM was produced of 12 MALT lymphoma samples, including 1 MALT lymphoma sample that expressed an IgM antibody fitting in a novel IGHV3‐30–encoded stereotypic IGHV subset. For 4 of the 12 IgM antibodies from MALT lymphoma samples, the somatically mutated IGHV and IGKV gene sequences were reverted to germline configurations. Their RF activity and binding affinity were determined by enzyme‐linked immunosorbent assay and surface plasmon resonance, respectively.

Results

Nine (75%) of the 12 IgM antibodies identified in patients with SS‐associated salivary gland MALT lymphoma displayed strong monoreactive RF activity. Reversion of the IGHV and IGKV mutations to germline configuration resulted in RF affinities for IgG that were significantly lower for 3 of the 4 somatically mutated IgM antibodies. In stereotypic IGHV3‐7/IGKV3‐15–encoded RFs, a recurrent replacement mutation in the IGKV3‐15–third complementarity‐determining region was found to play a pivotal role in the affinity for IgG‐Fc.

Conclusion

A majority of patients with SS‐associated salivary gland MALT lymphoma express somatically mutated BCRs that are selected for monoreactive, high‐affinity binding of IgG‐Fc. These data underscore the notion that soluble IgG, most likely in immune complexes in inflamed tissues, is the principal autoantigen in the pathogenesis of a variety of B cell lymphomas, particularly SS‐associated MALT lymphomas.
UCH‐L3 promotes non‐small cell lung cancer proliferation via accelerating cell cycle and inhibiting cell apoptosis
Authors: Li Guoping , Jin Xiaosheng , Zheng Jisheng , Jiang Na , Shi Wang
Published: March 2020

Ubiquitin C‐terminal hydrolase‐L3 (UCH‐L3) is a deubiquitinase that has a crucial role in oncogenesis. This study was aimed to explore the biological function of UCH‐L3 in non‐small cell lung cancer (NSCLC). Bioinformatics analysis was used to detect UCH‐L3 expression in NSCLC tissues and normal lung tissues, and to analyze the relationship between UCH‐L3 expression and survival of patients. qRT‐PCR and western blotting assays were used to detect UCH‐L3 expression in NSCLC tumor tissues and adjacent normal tissues. CCK‐8 assay was performed to examine the effect of UCH‐L3 on NSCLC cell proliferation. Flow cytometry assay was conducted to examine the effect of UCH‐L3 on NSCLC cell cycle and apoptosis. The expression of UCH‐L3 in NSCLC tissues was markedly higher than in normal lung tissues, and high expression of UCH‐L3 was positively associated with the poor survival of patients. UCH‐L3 knockdown significantly inhibited the proliferation of NSCLC cells, whereas UCH‐L3 overexpression had the opposite effect. Moreover, UCH‐L3 promoted NSCLC cells proliferation via accelerating cell cycle and inhibiting cell apoptosis. UCH‐L3 is upregulated in NSCLC and positively associated with the poor survival, and its expression contributes to NSCLC cell proliferation by accelerating cell cycle and inhibiting cell apoptosis.
Hydrocyclones as cell retention device for CHO perfusion processes in single‐use bioreactors
Authors: Bettinardi Ioná W. , Castan Andreas , Medronho Ricardo A. , Castilho Leda R.
Published: March 2020

In this study, a hydrocyclone (HC) especially designed for mammalian cell separation was applied for the separation of Chinese hamster ovary cells. The effect of key features on the separation efficiency, such as type of pumphead in the peristaltic feed pump, use of an auxiliary pump to control the perfusate flow rate, and tubing size in the recirculation loop were evaluated in batch separation tests. Based on these preliminary batch tests, the HC was then integrated to 50‐L disposable bioreactor bags. Three perfusion runs were performed, including one where perfusion was started from a low‐viability late fed‐batch culture, and viability was restored. The successive runs allowed optimization of the HC‐bag configuration, and cultivations with 20–25 days duration at cell concentrations up to 50 × 106 cells/ml were performed. Separation efficiencies up to 96% were achieved at pressure drops up to 2.5 bar, with no issues of product retention. To our knowledge, this is the first report in literature of high cell densities obtained with a HC integrated to a disposable perfusion bioreactor.
Core outcome set for uncomplicated acute appendicitis in children and young people
Authors: Sherratt F C , Allin B S R , Kirkham J J , Walker E , Young B , Wood W , Beasant L , Eaton S , Hall N J ,   Appendicitis Core Outcome Set Study Group, Rex D , Kalka K , Marven S , Rae J , Sotirios S , Braungart S , Gee O , Skerritt C , Lakshminarayanan B , Lisseter R , Brampton R , Luedekke L , Corbett H
Published: March 2020

Background

Research studies to inform clinical practice and policy in children and young people with appendicitis are hampered by inconsistent selection and reporting of outcomes. The aim of this study was to develop a core outcome set for reporting all studies of uncomplicated acute appendicitis in children and young people.

Methods

Systematic literature reviews, qualitative interviews with parents and patients treated for uncomplicated acute appendicitis, and a Study-Specific Advisory Group informed a long list of outcomes. Outcomes were then prioritized by stakeholders based in the UK (patients, parents, and paediatric and general surgeons) in an online three-round Delphi consensus process, followed by face-to-face consensus meetings.

Results

A long list of 40 items was scored by 147 key stakeholders in the first Delphi round, of whom 90 completed the two subsequent Delphi rounds. The final core outcome set comprises 14 outcomes: intra-abdominal abscess, reoperation (including interventional radiology procedure), readmission to hospital, bowel obstruction, wound infection, antibiotic failure, wound complication, negative appendicectomy, recurrent appendicitis, death, patient stress/psychological distress, length of hospital stay, time away from full activity and child's quality of life.

Conclusion

A core outcome set comprising 14 outcomes across five key domains has been developed for reporting studies in children and young people with uncomplicated acute appendicitis. Further work is required to determine how and when to measure these outcomes.
Bias reduction in the quantitative analysis of a target analyte present in a limited quantity in human plasma using dual‐mode heart‐cutting two‐dimensional liquid chromatography coupled with isotope dilution mass spectrometry
Authors: Hyung Seok‐Won , Kim Byungjoo
Published: March 2020

Dual‐mode heart‐cutting two‐dimensional liquid chromatography (DMHC 2D‐LC) was applied to isotope dilution mass spectrometry (IDMS) to reduce the bias in the quantitative analysis of a target analyte present in a limited quantity in human plasma. Based on a Waters I‐Class LC system, the DMHC 2D‐LC system was operated in one‐ and two‐dimensional modes to facilitate the determination of heart‐cutting time and the efficient trapping of the target LC eluate. Experiments to determine the feasibility of coupling with IDMS were performed with triple quadrupole mass spectrometry using folic acid standards and/or 13C5‐folic acid. To validate the performance of the DMHC 2D‐LC/IDMS system on a complex sample, human plasma was analyzed for folic acid and the result was compared with that obtained using conventional single‐column LC. The total run time of the DMHC 2D‐LC system was 20 min, the same as that of the single‐column LC system. The peak profile of the spiked 13C5‐folic acid obtained with single‐column LC/MS was affected by matrix effects, but resolved with DMHC 2D‐LC/MS, thus improving the accuracy of the analysis. The DMHC 2D‐LC/IDMS system showed reliable performance in analyzing the target analyte in human plasma, eliminating matrix effects and saving analysis time.
The relationship between lifestyle and serum neurofilament light protein in Huntington’s disease
Authors: Cruickshank Travis , Bartlett Danielle , Govus Andrew , Hannan Anthony , Teo Wei‐Peng , Mason Sarah , Lo Johnny , Ziman Mel
Published: March 2020

Objectives

Serum neurofilament light protein (NfL) is a promising marker of disease onset and progression in Huntington's disease (HD). This study investigated associations between lifestyle factors and NfL levels in HD mutation carriers compared to healthy age‐ and sex‐matched controls.

Materials and Methods

Participants included 29 HD mutation carriers and 15 healthy controls. Associations between serum NfL concentrations and lifestyle factors, including cardiorespiratory fitness, social network size and diversity, physical activity, cognitive reserve, smoking status, and alcohol consumption, were examined using a stepwise multivariable linear regression model.

Results

Higher NfL levels were associated with lower cognitive reserve, social network size and diversity and cardiorespiratory fitness in HD mutation carriers. Group × lifestyle factor effects were observed between lower serum NfL levels and a greater social network diversity.

Conclusion

These findings highlight a relationship between lifestyle factors and NfL levels in HD mutations carriers; however, longitudinal studies are required to confirm if these observed relationships persist over time.
Caesalpanins A–C, Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.
Authors: Wang De‐Sheng , Nie Wei , Jiang Ting‐Ting , Ding Lin‐Fen , Song Liu‐Dong , Wu Xing‐De , Zhao Qin‐Shi
Published: March 2020

Three dimeric cassane diterpenoids, caesalpanins A–C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D‐, 2D‐NMR, and HR‐ESI‐MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen‐containing cassane diterpenoid dimer linked through one ether bond between C‐19 and C‐20′. Caesalpanin B exhibited moderate cytotoxic activity against MCF‐7 cell lines with IC50 value of 29.98 μm. Caesalpanins A and B had weak inhibitory effects against LPS‐induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 μm with inhibitory rate of 36.01 % and 32.93 %, respectively.
LncRNA CYTOR attenuates sepsis‐induced myocardial injury via regulating miR‐24/XIAP
Authors: Chen Ting , Zhu Chunyan , Ye Chongyang
Published: March 2020

This work aims to investigate the function and mechanism of long non‐coding RNA (lncRNA) cytoskeleton regulator RNA (CYTOR) in myocardial injury induced by sepsis. The sepsis‐induced myocardial injury model in mice was established by intraperitoneal injection of LPS (10 mg/kg) in vivo, and cardiomyocyte H9c2 was treated with LPS to mimic sepsis in vitro. CYTOR expression and miR‐24 expression were detected by qRT‐PCR. After up‐regulation or down‐regulation of CYTOR and miR‐24 expression in the H9c2 cells, and the viability of the cells was detected via MTT assay, and cell apoptosis was detected by TUNEL assay. Western blot was applied to determine the expression level of caspase 3, Bax and X‐chromosome‐linked inhibitor of apoptosis (XIAP). Interaction between CYTOR and miR‐24 was determined by bioinformatics analysis, RT‐PCR and dual luciferase reporter assay. Interaction between miR‐24 and XIAP was determined through bioinformatics analysis, RT‐PCR, western blot and dual luciferase reporter assay. CYTOR was markedly down‐regulated. CYTOR interacted with miR‐24, and negatively regulated its expression level. Over‐expression of CYTOR or transfection of miR‐24 inhibitors significantly promoted viability and inhibited apoptosis of H9c2 cells, while the knockdown of CYTOR and transfection of miR‐24 mimics had opposite effects. CYTOR suppressed the expression level of apoptosis‐related proteins, but miR‐24 increased them. miR‐24 directly targeted the 3'UTR of XIAP, and suppressed it, and XIAP was modulated indirectly by CYTOR. Down‐regulation of CYTOR aggravates sepsis‐induced cardiac injury via regulating miR‐24 and XIAP.
Divergent Members of the Nitrogenase Superfamily: Tetrapyrrole Biosynthesis and Beyond
Authors: Ghebreamlak Selamawit M. , Mansoorabadi Steven O.
Published: March 2020

The nitrogenase superfamily constitutes a large and diverse ensemble of two‐component metalloenzymes. These systems couple the hydrolysis of ATP to the reduction of disparate substrates from diatomic gases (Mo and alternative nitrogenases) to photosynthetic pigments (protochlorophyllide and chlorophyllide oxidoreductases). Only very recently have the activities of the highly divergent and paraphyletic Group IV nitrogenases begun to be uncovered. This review highlights the first characterized member of this group, which was found to catalyze an unprecedented reaction in the coenzyme F430 biosynthetic pathway, and the catalytic potential of a superfamily that has yet to be fully explored.
Chlorophyllide a oxidoreductase Preferentially Catalyzes 8‐Vinyl Reduction over B‐Ring Reduction of 8‐Vinyl Chlorophyllide a in the Late Steps of Bacteriochlorophyll Biosynthesis
Authors: Yamamoto Haruki , Mizoguchi Tadashi , Tsukatani Yusuke , Tamiaki Hitoshi , Kurisu Genji , Fujita Yuichi
Published: March 2020

Bacteriochlorophyll a (BChl) is an essential pigment for anoxygenic photosynthesis. In late steps of the BChl biosynthesis of Rhodobacter capsulatus, the C8 vinyl group and C7=C8 double bond of 8‐vinyl chlorophyllide a (8 V‐Chlide) are reduced by a C8 vinyl reductase (8VR), BciA, and a nitrogenase‐like enzyme, chlorophyllide a oxidoreductase (COR), respectively, to produce 3‐vinyl‐bacteriochlorphyllide a. Recently, we discovered 8VR activity in COR. However, the kinetic parameters of the COR 8VR activity remain unknown, while those of the COR C7=C8 reductase activity and BciA have been reported. Here, we determined the kinetic parameters of COR 8VR activity by using 8 V‐Chlide. The Km value for 8 V‐Chlide was 1.4 μM, which is much lower than the 6.2 μM determined for the C7=C8 reduction of Chlide. The kinetic parameters of the dual activities of COR suggest that COR catalyzes the reduction of the C8 vinyl group of 8 V‐Chlide preferentially over C7=C8 reduction when both substrates are supplied during BChl biosynthesis.
Functional Characterisation of ClpP Mutations Conferring Resistance to Acyldepsipeptide Antibiotics in Firmicutes
Authors: Malik Imran T. , Pereira Rebeca , Vielberg Marie‐Theres , Mayer Christian , Straetener Jan , Thomy Dhana , Famulla Kirsten , Castro Helena , Sass Peter , Groll Michael , Brötz‐Oesterhelt Heike
Published: March 2020

Acyldepsipeptide (ADEP) is an exploratory antibiotic with a novel mechanism of action. ClpP, the proteolytic core of the caseinolytic protease, is deregulated towards unrestrained proteolysis. Here, we report on the mechanism of ADEP resistance in Firmicutes. This bacterial phylum contains important pathogens that are relevant for potential ADEP therapy. For Staphylococcus aureus, Bacillus subtilis, enterococci and streptococci, spontaneous ADEP‐resistant mutants were selected in vitro at a rate of 10−6. All isolates carried mutations in clpP. All mutated S. aureus ClpP proteins characterised in this study were functionally impaired; this increased our understanding of the mode of operation of ClpP. For molecular insights, crystal structures of S. aureus ClpP bound to ADEP4 were determined. Well‐resolved N‐terminal domains in the apo structure allow the pore‐gating mechanism to be followed. The compilation of mutations presented here indicates residues relevant for ClpP function and suggests that ADEP resistance will occur at a lower rate during the infection process.
Engineering a Highly Active Sucrose Isomerase for Enhanced Product Specificity by Using a “Battleship” Strategy
Authors: Pilak Patrick , Schiefner André , Seiboth Judith , Oehrlein Johannes , Skerra Arne
Published: March 2020

The sucrose isomerase SmuA from Serratia plymuthica efficiently catalyses the isomerisation of sucrose into isomaltulose, an artificial sweetener used in the food industry. However, the formation of a hygroscopic by‐product, trehalulose, necessitates additional separation to obtain a crystalline product. Therefore, we have improved the product specificity of SmuA by first introducing a few exploratory amino acid exchanges around the active site and investigating their influence. Then, we devised a second set of mutations, either at promising positions from the preceding cycle, but with a different side chain, or at alternative positions in the vicinity. After seven iterative cycles involving just 55 point mutations, we obtained the triple mutant Y219L/D398G/V465E which showed 2.3 times less trehalulose production but still had high catalytic efficiency (kcat/KM=11.8 mM−1 s−1). Not only does this mutant SmuA appear attractive as an industrial biocatalyst, but our semirational protein‐engineering strategy, which resembles the battleship board game, should be of interest for other challenging enzyme optimization endeavours.
In Vitro Selection of New DNA Aptamers for Human Vascular Endothelial Growth Factor 165
Authors: Manochehry Sepehr , Gu Jimmy , McConnell Erin M. , Salena Bruno J. , Li Yingfu
Published: March 2020

Two DNA aptamers that bind the heparin‐binding domain (HBD) of the human vascular endothelial growth factor 165 (VEGF‐165) have been previously reported. Although VEGF‐165 is a homodimeric protein and the two aptamers have different sequences and secondary structures, the aptamers appear to occupy the same binding site and cannot form a 2 : 1 aptamer/protein complex, thus making them unsuitable for creating a higher‐affinity dimeric DNA aptamer. This has motivated us to conduct a new in vitro selection experiment to search for new VEGF‐165‐binding DNA aptamers with different properties. We undertook a multistream selection strategy in which the concentration of VEGF‐165 was varied significantly. We carried out 11 rounds of selection, and next‐generation sequencing was conducted for every round in each stream. From comprehensive sequence analysis, we identified four classes of DNA aptamers, of which two were reported before, but two are new DNA aptamers. One of the new aptamers exhibits a unique property that has never been observed before: it is capable of forming the 2 : 1 aptamer/protein complex with VEGF‐165. This work has expanded the repertoire of VEGF‐165‐binding DNA aptamers and creates a possibility to engineer a higher affinity homodimeric aptamer for VEGF‐165.
Promotion and Inhibition of the Oxidase‐Mimicking Activity of Nanoceria by Phosphate, Polyphosphate, and DNA
Authors: Zhao Yilin , Li Haotian , Lopez Anand , Su Haijia , Liu Juewen
Published: March 2020

Nanoceria (CeO2 nanoparticles) is an extensively studied nanozyme with interesting oxidase‐mimicking activity. As they can work in the absence of toxic and unstable H2O2, CeO2 nanoparticles have been widely used in biosensing. CeO2 nanoparticles often encounter phosphate‐containing molecules that can affect their catalytic activity, and various reports exist in the literature showing both promoted and inhibited activity. In this work, we systematically studied five types of phosphate: orthophosphate, pyrophosphate, triphosphate, trimetaphosphate, and a polyphosphate with 25 phosphate units (Pi25). In addition, DNA oligonucleotides of various length and sequence. DNA was included as they contain a phosphate backbone that can strongly adsorb on nanoceria. We observed that a high concentration of DNA in acetate buffer inhibited activity, whereas a low concentration of DNA in phosphate buffer increased activity. The change of activity was also related to the type of substrate and related to the aggregation of CeO2. These discoveries provide an important understanding for the further use of CeO2 nanoparticles in biosensor development, materials science, and nanotechnology.
Responsive Fluorophore Aggregation Provides Spectral Contrast for Fluorescence Lifetime Imaging
Authors: Schleyer Kelton A. , Datko Benjamin D. , Burnside Brandon , Cui Chao , Ma Xiaowei , Grey John K. , Cui Lina
Published: March 2020

Fluorophores experience altered emission lifetimes when incorporated into and liberated from macromolecules or molecular aggregates; this trend suggests the potential for a fluorescent, responsive probe capable of undergoing self‐assembly and aggregation and consequently altering the lifetime of its fluorescent moiety to provide contrast between the active and inactive probes. We developed a cyanobenzothioazole‐fluorescein conjugate (1), and spectroscopically examined the lifetime changes caused by its reduction‐induced aggregation in vitro. A decrease in lifetime was observed for compound 1 in a buffered system activated by the biological reducing agent glutathione, thus suggesting a possible approach for designing responsive self‐aggregating lifetime imaging probes.
Ethinylestradiol and its effects on the macrophages in the prostate of adult and senile gerbils
Authors: Castro Nayara F. C. , Falleiros‐Júnior Luiz R. , Zucão Mariele I. , Perez Ana P. S. , Taboga Sebastião R. , Santos Fernanda C. A. , Vilamaior Patrícia S. L.
Published: March 2020

Prenatal and neonatal exposure to estrogenic compounds, such as ethinylestradiol (EE), promotes a variety of developmental disorders, including malformations and alterations in the morphology of glands, such as the prostate gland. Therefore, the aim of this study was to evaluate the morphological effects of neonatal exposure to EE on prostatic tissue and on the identification and quantification of gerbil gland macrophages in adult and senile Mongolian gerbils. The animals were exposed to EE (10 μg/kg/day) and to the vehicle, mineral oil (100 μL) (control group) during the first 10 days of postnatal life (lactation period). Adult gerbils were euthanized at 120 days and senile gerbils at 12 months of age. Our findings permitted verification of the presence of areas with proliferative foci in the prostate glandular portions in the adult and senile animals exposed to EE. There was also an increase in macrophages in the prostate tissue of adult and senile gerbils; these cell types alter the stromal microenvironment and possibly modify the interactions between the epithelium and stroma. Neonatal exposure to EE changes the pattern of prostatic development, leading to alterations in the arrangement of cells, including macrophages, and may be related to the onset of proliferative disorders in the prostate of adult gerbils and during aging.
Comparison of post‐stent optical coherence tomography findings among three subtypes of calcified culprit plaques in patients with acute coronary syndrome
Authors: Nakajima Akihiro , Araki Makoto , Kurihara Osamu , Minami Yoshiyasu , Soeda Tsunenari , Yonetsu Taishi , Crea Filippo , Takano Masamichi , Higuma Takumi , Kakuta Tsunekazu , Adriaenssens Tom , Lee Hang , Nakamura Sunao , Jang Ik‐Kyung
Published: March 2020

Objectives

To compare the postprocedural optical coherence tomography (OCT) findings and in‐hospital outcomes among the three subtypes of calcified plaques: eruptive calcified nodules, superficial calcific sheet, and calcified protrusion.

Background

Recently, three subtypes of calcified culprit plaques were reported in patients with acute coronary syndrome (ACS). How these subtypes respond to stenting is unknown.

Methods

ACS patients with calcified plaque at the culprit lesion were selected from our database. OCT findings at baseline and after stent implantation were compared.

Results

In the final analysis, 87 cases were included. Preprocedural OCT showed eruptive calcified nodules in 19 (21.8%) cases, superficial calcific sheet in 63 (72.4%), and calcified protrusion in 5 (5.7%). Stent edge dissection (SED) and incomplete stent apposition (ISA) were frequently observed in the eruptive calcified nodules group compared to superficial calcific sheet or calcified protrusion (SED; 47.4% vs. 17.5% vs. 20.0%; p = .032, ISA; 94.7% vs. 58.7% vs. 0.0%; p < .001). The superficial calcific sheet group had the smallest minimal stent area (MSA) among the three groups (eruptive calcified nodules vs. superficial calcific sheet vs. calcified protrusion: 6.29 ± 2.41 vs. 4.72 ± 1.37 vs. 6.56 ± 1.13; p = .007). The superficial calcific sheet group had a higher rate of periprocedural myocardial infarction compared to the eruptive calcified nodules group (60.3% vs. 31.6%; p = .028).

Conclusions

This study demonstrated eruptive calcified nodules are associated with higher incidence of SED and ISA, whereas superficial calcific sheets are associated with small MSA and higher periprocedural myocardial infarction.
Institutional learning experience for combined edge‐to‐edge tricuspid and mitral valve repair
Authors: Mahowald Madeline K. , Pislaru Sorin V. , Reeder Guy S. , Padang Ratnasari , Michelena Hector I. , Mankad Sunil V. , Maalouf Joseph F. , Guerrero Mayra , Alkhouli Mohamad , Rihal Charanjit S. , Eleid Mackram F.
Published: March 2020

Background

Transcatheter edge‐to‐edge repair with MitraClip is only approved for treatment of mitral regurgitation but is increasingly used to treat concomitant tricuspid regurgitation (TR) due to its common coexistence and association with poor outcomes. This study aimed to describe the learning curve associated with the challenge of off‐label treatment of concomitant TR.

Methods

This is a retrospective review of initial and consecutive patients who underwent combined edge‐to‐edge repair of mitral and tricuspid valves (TVs) at our institution from August 2017 to October 2019.

Results

Repair of both valves with MitraClip was performed in 22 patients (median age 81.5 years, 32% female). Mean procedure time was 176 ± 47 min; mean fluoroscopy time was 65 ± 24 min. Procedure duration in the first tertile was significantly longer (223 ± 13 min) than in the third tertile (143 ± 23 min, p = .0003). Median number of total clips placed per case was 3; in 15 patients (68%), the anterior and septal leaflets of the TV were clipped. The average changes in mean right atrial (RA) and left atrial (LA) pressures were −1.7 ± 2.5 mmHg (p = .0080) and −3.2 ± 4.6 mmHg (p = .0045), respectively. The average changes in RA and LA V‐wave heights were −3.3 ± 4.0 mmHg (p = .0009) and −8.1 ± 9.9 mmHg (p = .038), respectively. There was a significant trend toward decreasing residual TR over the course of the series (p = .046). At 30 days, survival was 100% and mean NYHA class decreased from 2.8 to 1.8 (p < .0001).

Conclusions

Combined edge‐to‐edge tricuspid and mitral valve repair is safe and feasible. With experience, procedure duration and residual TR decreased.
Sub‐5 nm Intermetallic Nanoparticles Confined in Mesoporous Silica Wells for Selective Hydrogenation of Acetylene to Ethylene
Authors: Maligal‐Ganesh Raghu V. , Pei Yuchen , Xiao Chaoxian , Chen Minda , Goh Tian Wei , Sun Weijun , Wu Jiashu , Huang Wenyu
Published: March 2020

We report the synthesis and catalytic application of intermetallic PtSn nanoparticles confined in MSWs (Mesoporous Silica Wells) in the semi‐hydrogenation of acetylene. Platinum nanoparticles with a size of 2.9 nm supported on amine‐functionalized ∼180 nm silica spheres were enmeshed in a mesoporous silica shell. After the addition of tin via a polyol synthesis method, we obtained the final PtSnx@MSW (x=0.30, 0.50, 0.70, 1.0 and 2.0). Owing to the mesoporous encapsulation the sub‐5 nm bimetallic particles are shown to be monodisperse and well protected against aggregation on the silica sphere even under high‐temperature treatment conditions. In the gas phase semi‐hydrogenation of acetylene, the PtSn@MSW with Sn/Pt molar ratios equal to or greater than one displayed higher selectivity to ethylene. Meanwhile, increasing Sn content decreases acetylene conversion. The intermetallic PtSn@MSW catalysts also displayed long‐term stability and regenerability due to the confined environment provided by MSW.
Plasmonic Electrons‐Driven Solar‐to‐Hydrocarbon Conversion over Au NR@ZnO Core‐Shell Nanostructures
Authors: Shen Jinni , Chen Zhenye , Han Shitong , Zhang Hongwen , Xu Hailing , Xu Chao , Ding Zhengxin , Yuan Rusheng , Chen Jinquan , Long Jinlin
Published: March 2020

This work demonstrates the long‐range redox reactivity of gold plasmon‐generated hot electrons for solar‐driven CO2 conversion. A series of Au NR@ZnO core‐shell photocatalysts with a tunable shell thickness are rationally designed to achieve the solar‐to‐CH4 conversion, where the hot plasmonic electrons‐induced photoreduction takes place on the polar oxide moiety. The shell thickness‐independent activity implies that the core, gold nanorods, plays a dominant role in the CH4 generation. The ZnO metal oxide semiconductor shell is beneficial to prolong the lifetime of hot electrons, thereby enhancing the photocatalytic efficiency. However, the thickness of ZnO shell is not relevant to the production rate. Both of these two parts are co‐excited by solar light and synergetic enhance the photocatalytic activity.