bluuebunny/crossref_metadata_2025 huggingface dataset:
Thiazolidinediones and risk for atherosclerosis: pleiotropic effects of PPARγ agonism
Authors: Patle Chetan B , De Lemos James A , Wyne Kathleen L , McGuire Darren K
Published: May 2007

Despite advances in the development of anti-hyper-glycaemic drugs and a greater focus on cardiovascular risk modification for patients with diabetes, cardiovascular disease remains the most common complication of type 2 diabetes. Since their initial availability in 1997, the thiazolidinediones have become one of the most commonly prescribed classes of medications for type 2 diabetes. In addition to glucose control, the thiazolidinediones have a number of pleiotropic effects on myriad traditional and non-traditional risk factors for cardiovascular disease, and hold promise with regard to modification of cardiovascular risk. In a recently reported large-scale clinical trial, pioglitazone was associated with improved cardiovascular outcomes in patients with type 2 diabetes and prevalent atherosclerotic disease.

In this review, we summarise the experimental, pre-clinical and clinical data regarding the effects of the thiazolidinediones on cardiovascular risk factors and clinical outcomes.
Postprandial hyperglycaemia and vascular damage - the benefits of acarbose
Authors: Båvenholm Peter N , Efendic Suad
Published: May 2007

Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in diabetes. Epidemiology shows that hyperglycaemia is a continuous CVD risk factor and that two-hour postprandial glucose levels are more strongly associated with CVD than fasting glucose. Good glycaemic control is proven to reduce the risk of microvascular complications, but equivalent evidence for CVD risk reduction is lacking. However, in the Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM), acarbose reduced the risk of diabetes in those with impaired glucose tolerance by 36% (p=0.0017) and the risk of any cardiovascular event by 49% (p=0.0326) versus placebo. Furthermore, a meta-analysis of trials of acarbose in patients with type 2 diabetes suggests a significant reduction of CVD events.

This review examines evidence that postprandial hyperglycaemia plays a major role in vascular damage, particularly through non-traditional risk factors such as oxidative stress and subclinical inflammation, and how acarbose may prevent this damage.
The association between hyperglycaemia and elevated troponin levels on mortality in acute coronary syndromes
Authors: Gale Christopher P , Kashinath Chetan , Brooksby Paul
Published: May 2007

Diabetes is associated with increased cardiovascular morbidity and mortality. We studied the relationship between hyperglycaemia, troponin I concentrations and one-year mortality in 498 subjects admitted to hospital with an acute coronary syndrome. The proportion of deaths was higher in those with hyperglycaemia (random glucose > 11. 1 mmol/L) compared to those without (27% and 12%, respectively, Chi-squared test = 9. 84, p=0. 002). There was a difference in troponin I concentration on admission between those patients who were alive and dead (median and interquartile range 0. 14 [0 to 3. 90] and 2. 98 [0. 23 to 18. 53] respectively, p<0. 001) and the risk of death was elevated in those with a myocardial infarction compared to those without (relative risk = 1. 85, 95% confidence intervals 1. 55 to 2. 21). Despite adherence to guidelines for the management of acute coronary syndromes, the presence of hyperglycaemia confers a significant long-term mortality disadvantage.
Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome
Authors: Denke Margo , Pearson Thomas , McBride Patrick , Gazzara Russell A , Brady William E , Tershakovec Andrew M
Published: May 2007

This analysis of the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial examined the effectiveness and safety of ezetimibe 10 mg added to ongoing statin therapy in patients with diabetes, metabolic syndrome without diabetes, or neither disorder who had low-density lipoprotein cholesterol (LDL-C) levels exceeding National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) goals. After six weeks of treatment, ezetimibe added to statin reduced LDL-C in patients with diabetes by 28%, metabolic syndrome by 24%, or neither by 26%, compared with a 3% reduction for placebo for each group. In each group, more patients receiving ezetimibe plus statin reached LDL-C goal (67–74%) compared with those receiving placebo plus statin (19–22%). Other parameters demonstrating greater improvement with ezetimibe included triglycerides, apolipoprotein (Apo)B/Apo A-I ratio, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein. Ezetimibe plus statin was well tolerated in each group. Ezetimibe added to ongoing statin therapy offers a new treatment option that is consistently effective in improvement of lipid profiles and attainment of LDL-C goals in patients with or without diabetes or metabolic syndrome.
Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes
Authors: Green Brian D , Flatt Peter R , Bailey Clifford J
Published: May 2007

Inhibitors of the enzyme dipeptidyl peptidase IV (DPP IV) provide a strategy for the treatment of type 2 diabetes. DPP IV rapidly inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP IV prolongs and enhances the activity of endogenous GLP-1 and GIP, which serve as important prandial stimulators of insulin secretion and regulators of blood glucose control. In clinical trials DPP IV inhibitors (or ‘gliptins’) have shown efficacy and tolerability in the management of hyperglycaemia in type 2 diabetes, without causing weight gain or hypoglycaemia.
The sibutramine metabolite M2 improves muscle glucose uptake and reduces hepatic glucose output: preliminary data
Authors: Coletta Dawn K , Bates Sarah H , Jones Robert B , Bailey Clifford J
Published: May 2007

The satiety agent sibutramine acts in part through a primary amine metabolite, M2. To investigate whether M2 could affect glycaemia independently of satiety and weight loss, groups of normal mice received a single dose of M2 (1 or 10 mg/kg) and food was withheld. Compared with controls (who received vehicle only), M2 (10 mg/kg) decreased basal plasma glucose concentrations, with a maximal decrease of about 25% at 4-8 hours (p<0.05). Soleus muscles were isolated from the mice at intervals: insulin-mediated glucose uptake by the muscles from controls progressively decreased over 24 hours whereas uptake was maintained by muscles from M2-treat-ed mice. Hepatic gluconeogenesis was reduced about 40% by liver snips isolated from M2-treated mice after 24 hours (p<0.05).

These preliminary results suggest that the M2 metabolite of sibutramine can reduce glycaemia, maintain insulin-mediated muscle glucose uptake and reduce hepatic gluconeogenesis independently of satiety and weight loss.
Treating insulin resistance: future prospects
Authors: Bailey Clifford J
Published: May 2007

Insulin resistance typically reflects multiple defects of insulin receptor and post-receptor signalling that impair a diverse range of metabolic and vascular actions. Many potential intervention targets and compounds with therapeutic activity have been described. Proof of principle for a non-peptide insulin mimetic has been demonstrated by specific activation of the intracellular B-subunit of the insulin receptor. Potentiation of insulin action has been achieved with agents that enhance phosphorylation and prolong the tyrosine kinase activity of the insulin receptor and its protein substrates after activation by insulin. These include inhibitors of phosphatases and serine kinases that normally prevent or terminate tyrosine kinase signalling. Additional approaches involve increasing the activity of phos-phatidylinositol 3-kinase and other downstream components of the insulin signalling pathways.

Experimental interventions to remove signalling defects caused by cytokines, certain adipocyte hormones, excess fatty acids, glucotoxicity and negative feedback by distal signalling steps have also indicated therapeutic possibilities. Several hormones, metabolic enzymes, minerals, co-factors and transcription co-activators have shown insulin-sensitising potential.

Since insulin resistance affects many metabolic and cardiovascular diseases, it provides an opportunity for simultaneous therapeutic attack on a broad front.
Multi-modal magnetic resonance imaging quantifies atherosclerosis and vascular dysfunction in patients with type 2 diabetes mellitus
Authors: Lee Justin MS , Shirodaria Cheerag , Jackson Clare E , Robson Matthew D , Antoniades Charalambos , Francis Jane M , Wiesmann Frank , Channon Keith M , Neubauer Stefan , Choudhury Robin P
Published: May 2007

Vascular magnetic resonance imaging (MRI) is emerging as a powerful research tool. We studied 18 patients with type 2 diabetes mellitus and 20 controls (all with coronary artery disease). MRI measured distensibility, pulse wave velocity (PWV) and atherosclerosis in the aorta, and brachial artery flow-mediated dilatation (FMD). Patients with diabetes showed lower aortic distensibility (2.1 × 10-3 vs. 3.5 × 10-3 mmHg-1, p<0.01), faster PWV (8.8 vs., 6.2 m/s, p<0.01) and impaired FMD (8.5% vs. 13.8%, p<0.05). Diabetes was an independent negative predictor of distensibility. Aortic atherosclerosis was similar in the two groups. There was a negative correlation between aortic distensibility and atherosclerosis in control subjects only, suggesting that other factors such as protein cross-linking may explain lower aortic distensibility in diabetes. MRI provides comprehensive vascular phenotyping in patients with type 2 diabetes and is likely to be useful in studies of disease progression and drug therapy.
Influence of metabolic risk factors on the presence of carotid artery disease in patients with type 2 diabetes and coronary artery disease
Authors: Bosevski Marijan , Borozanov Vladimir , Georgievska-Ismail Ljubica
Published: May 2007

The aim of the study was to evaluate the prevalence of carotid artery disease in type 2 diabetes patients with coronary artery disease, and to establish the influence of metabolic factors on its occurrence.

In all, 145 patients (aged 59.85±8.43 years, diabetes duration 8.89±6.29 years) were randomly selected in a cross-sectional study. Carotid ultrasound was used for evaluation of the presence of carotid plaque (CP) and stenosis (CS). A logistic regression model was constructed to define the influence of risk factors - arterial hypertension, systolic blood pressure, weight, waist to hip ratio, high blood glucose and plasma lipid levels.

Carotid artery disease was present in these patients with a prevalence of 81.9% for CP, 25.2% for unilateral CS and 13.5% for bilateral CS. The low-density lipoprotein (LDL) cholesterol level was an independent predictor for CS (OR 1.936; 95% CI 1.241-3.026). Non-high density lipoprotein (HDL) cholesterol (OR 1.374; 95% CI 1.035-1.825) and glycaemia (OR 1.214; 95% CI 1.022-1.442) were predictors for carotid plaque.
Simultaneous Pigmented Paravenous Retinochoroidal Atrophy and Retinitis Pigmentosa in the Contralateral Eye
Authors: Plaza Daniel Gomez , Jelstrup Anniken Bures , Navarro Rafael
Published: March 2024

This case report describes a simultaneous diagnosis of paravenous retinochoroidal atrophy and retinitis pigmentosa in the same patient.
Investigations on the Influence of Catalyst Geometry on Emission Reduction in Small‐Scale Combustion System
Authors: Bissinger Dominik , Hoferecht Frank , Roppertz Andreas
Published: March 2024

Legal regulations for exhaust gas treatment in small‐scale combustion systems demand both emission and dust reduction. Simultaneously removing both pollutants using catalysts presents a significant challenge due to constraints on the very low allowed pressure drop over the catalyst. It can be demonstrated that the total oxidation of CO, as one of the main pollutants in the combustion of biogenic materials, in small‐scale combustion systems can be quantitatively achieved using precious metal‐based catalysts based on Pt/CeO2/TiO2. The highest CO conversion rate can be observed with a 233 cpsi honeycomb catalyst, whereas the foam ceramic catalysts with 30, 20, and 10 ppi show progressively decreasing activity. However, concerning dust reduction, it can be demonstrated that the ceramic foam with 10 ppi is superior, as evidenced in real‐world experiments conducted on an Leda Novia W small‐scale combustion device with 8 kW combustion capacity. Particle deposition on the catalysts is observed with all catalysts, whereby catalysts with small pores show rapid pore blockage. It is observed that only with the 10 ppi foam catalyst, dust deposition does not lead to pore blockage, allowing a reduction in dust of more than 50% over the measurement cycle.
Natural Phenolic‐Metal Framework Strengthened Mesona Chinensis Polysaccharides Microgels for Improved Viability of Probiotics to Alleviate the Liver Injury and Gut Microbiota Dysbiosis
Authors: Zhang Huijuan , Zhang Jipeng , Liu Bin , Xiao Jie , Stuart Martien A. Cohen , Hou Guohua , Zhang Hongru , Liang Shuang , Li Zekun , Wang Qimeng , Chen Shanan , Li Pinglan , Li Xing , Li Yuan
Published: March 2024

Oral probiotics meet challenges during processing, storage, and gastrointestinal harsh conditions. Polysaccharide‐based hydrogels delivery system is promising in probiotic protection, but its semi‐solid and weak strength, and often requires additional cross‐links to solidify its structure. Herein a ferric ion co‐crosslinked microgel of Mesona chinensis polysaccharides and mechanically strengthened by phenolic‐metal frameworks of naturally bound brown bioactives is designed. These microgels has an intact structure in acidic condition and ruptured only at pH neutral conditions which can responsively release highly viable probiotics with high mucoadhesion and colonization. Brown bioactives are naturally bound to polysaccharides (MCPC) by hydrophobic interactions and hydrogen bonding, and they exhibited outstanding anti‐inflammatory and antioxidant properties. Moreover, these brown bioactives are the precise prebiotics which can specifically improve the abundance of Akkermansia genus in gut in vivo. Then, the probiotics Akkermansia muciniphila (AKK) are loaded into brown bioactives frameworks strengthened microgels. There is a more synergistic healthy benefit between MCPC components and loaded AKK compared with free and pasteurized AKK. MCPC microgels can deliver high viable AKK specifically to gut consequently modulating the microbiota balance, and protecting the intestinal barriers. MCPC microgels also delivered the antioxidant brown bioactives specifically into liver to alleviate the hepatic oxidative stress and inflammation.
Electron‐Donating Cu Atoms Induced High Proton Supply and Anti‐Poisoning Ruthenium Clusters for Superior Direct Seawater Hydrogen Production
Authors: Yang Chengdong , Wu Zihe , Zheng Yijuan , Gao Yun , Ma Tian , Zeng Zhiyuan , Wang Yi , Cheng Chong , Li Shuang
Published: March 2024

Direct seawater hydrogen production via electrolysis would be a transformative technology for large‐scale pathways for future sustainable energy systems. However, prohibiting the formation of insoluble hydroxides and promoting proton supply at the electrode‐seawater interface are extremely desirable but remain challenging. Herein, inspired by the dual‐metal pair sites in natural enzyme, the de novo design of an efficient, robust, and precise electron‐donating Cu‐modulated ruthenium clusters on porous carbon matrix (Cu@Runc‐C) is reported as a high proton supply and anti‐poisoning cathode material for superior direct seawater hydrogen production. Benefitting from the unique Cu@Runc pair sites, the cathode exhibits particularly high hydrogen evolution activities with ultralow overpotentials to reach a high current density of 300 mA cm−2 in both alkaline (115 mV) and seawater (459 mV) electrolytes, and notably, the cathode can maintain superior long‐lasting stability in seawater electrolysis. The mechanism exploration demonstrates that the ruthenium cathode with Cu@Runc pair sites exhibits low oxophilic and fast proton‐transferring local reaction environments to prohibit the formation of insoluble precipitates and provide efficient proton supply within the electrode‐seawater interface. It is expected that the proposed bioinspired regulation strategy offers a new pathway for constructing efficient, robust, and selective cathode materials for scalable seawater hydrogen production.
Conversion of Layered WS2 Crystals into Mixed‐Domain Electrochemical Catalysts by Plasma‐Assisted Surface Reconstruction
Authors: Park Jiheon , Cho Iaan , Jeon Hotae , Lee Youjin , Zhang Jian , Lee Dongwook , Cho Min Kyung , Preston Daniel J. , Shong Bonggeun , Kim In Soo , Lee Won‐Kyu
Published: March 2024

Electrocatalytic water splitting is crucial to generate clean hydrogen fuel, but implementation at an industrial scale remains limited due to dependence on expensive platinum (Pt)‐based electrocatalysts. Here, an all‐dry process to transform electrochemically inert bulk WS2 into a multidomain electrochemical catalyst that enables scalable and cost‐effective implementation of the hydrogen evolution reaction (HER) in water electrolysis is reported. Direct dry transfer of WS2 flakes to a gold thin film deposited on a silicon substrate provides a general platform to produce the working electrodes for HER with tunable charge transfer resistance. By treating the mechanically exfoliated WS2 with sequential Ar‐O2 plasma, mixed domains of WS2, WO3, and tungsten oxysulfide form on the surfaces of the flakes, which gives rise to a superior HER with much greater long‐term stability and steady‐state activity compared to Pt. Using density functional theory, ultraefficient atomic sites formed on the constituent nanodomains are identified, and the quantification of atomic‐scale reactivities and resulting HER activities fully support the experimental observations.
Gradient High‐Q Dielectric Metasurfaces for Broadband Sensing and Control of Vibrational Light‐Matter Coupling
Authors: Richter Felix Ulrich , Sinev Ivan , Zhou Senlu , Leitis Aleksandrs , Oh Sang‐Hyun , Tseng Ming Lun , Kivshar Yuri , Altug Hatice
Published: March 2024

Surface‐enhanced infrared absorption spectroscopy (SEIRA) has emerged as a powerful technique for ultrasensitive chemical‐specific analysis. SEIRA can be realized by employing metasurfaces that can enhance light‐matter interactions in the spectral bands of molecular vibrations. Increasing sample complexity emphasizes the need for metasurfaces that can operate simultaneously at different spectral bands, both accessing rich spectral information over a broad band, and resolving subtle differences in the absorption fingerprints through narrow‐band resonances. Here, a novel concept of resonance‐gradient metasurfaces is introduced, where the required spectral selectivity is achieved via local high‐quality‐factor (high‐Q) resonances, while the continuous coverage of a broad band is enabled by the gradual adjustment of the unit‐cell dimensions along the planar structure. The highly tailorable design of the gradient metasurfaces provides flexibility for shaping the spectral sampling density to match the relevant bands of target analytes while keeping a compact device footprint. The versatility of the gradient metasurfaces is demonstrated through several sensing scenarios, including polymer mixture deconvolution, detecting a multistep bioassay, and identification of the onset of vibrational strong coupling regime. The proposed gradient‐resonance platform significantly contributes to the rapidly evolving landscape of nonlocal metasurfaces, enabling applications in molecular detection and analysis of fundamental light‐matter interaction phenomena.
Air‐Stable Bis‐Cyclometallated Iridium Catalysts for Ortho‐Directed C(sp2)−H Borylation
Authors: Zakis Janis M. , Messinis Antonis M. , Ackermann Lutz , Smejkal Tomas , Wencel‐Delord Joanna
Published: March 2024

We report a class of isolable bis‐cyclometallated iridium precatalysts (ImIr) and their use in regioselective ortho−C−H borylation of aromatic, heteroaromatic, acrylic, and aliphatic systems. The catalysts consist of two imine ligands and an acetate coordinated to an iridium (III) center. The isolable character of ImIr warrants its compatibility with high‐throughput experimentation, a prerequisite for applications in late‐stage functionalization (LSF) of complex substrates. Initial mechanistic studies point towards an inner‐sphere mechanism involving bis‐cyclometallated species shedding light on the general mechanistic understanding of ortho‐selective C−H borylations.
An Iron‐Catalyzed Three‐Component Radical Cascade Cyclization to Access Cyanoalkylsulfonyl Quinolino‐Quinazolinones
Authors: Mohamathu Ghouse Abuthayir , Tarun Uppalam , Maheswari Bathula , Murthy Akondi Srirama
Published: March 2024

An iron(II)‐catalyzed cascade reaction, involving cyanoalkylsulfonylation and cyclization, has been devised to enable the synthesis of functionalized sulfonylated quinolino‐quinazolinone alkyl nitriles. This three‐component radical transformation exhibits excellent chemo‐ and regioselectivity while functioning without the need for external oxidizing or reducing agents. The cost‐effectiveness of this catalytic system, together with its broad substrate application, which includes drug molecule derivatives, make this approach efficient and adaptable.
Approaches to Control and Monitor Protease Levels in Chronic Wounds
Authors: Kolahreez Davood , Ghasemi‐Mobarakeh Laleh , Liebner Falk , Alihosseini Farzaneh , Quartinello Felice , Guebitz Georg M. , Ribitsch Doris
Published: March 2024

Some wounds do not follow the typical healing trajectory and show very little, if any, progress. They dreadfully threaten the patients' quality of life and may even lead to limb amputation and death. Several interrelated systemic and local factors may cause a delay in wound healing. The microenvironment of these wounds can be different from wounds that heal spontaneously or with standard treatment. As discussed in the present work, proteases’ levels or activity can be elevated in some cases of chronic ulcers; infection can aggravate the situation. A detailed overview of the proteases’ effect on wound healing is presented in this work. Assuming untimely or irregularly excessive proteolytic activity plays a pathological role, some researchers targeted attenuation of protease level as a strategy to promote healing. This can be done via different approaches, including physical removal, inhibiting their activity, and controlling their expression directly through gene silencing or indirectly, for instance, by resolving infection. Apart from targeting protease modulation as a therapeutic strategy, many studies have examined the protease state to gain insights into the underlying mechanisms by which a remedy, dressing, or specific therapy has affected the healing process. This study aims to provide an overview of the studies in these two categories. Of course, various proteases are involved in the healing process, but in each study, usually, only one or some of them are investigated; matrix metalloproteinase‐2 (MMP‐2), MMP‐9, and human neutrophil elastase (HNE) are among them. Furthermore, in some cases, cumulative proteolytic activity is evaluated in terms of gelatinolytic, collagenolytic, or caseinolytic activity, which is also absolutely beneficial. Some research groups have considered the potential of proteases as a diagnostic or prognostic biomarker and have tried to develop some sensors or indicators; this topic is also covered in the present work.
Boosting Zinc Hybrid Supercapacitor Performance via Thiol Functionalization of Graphene‐Based Cathodes
Authors: Valentini Cataldo , Montes‐García Verónica , Ciesielski Artur , Samorì Paolo
Published: March 2024

Zinc hybrid supercapacitors (Zn‐HSCs) hold immense potential toward the next‐generation energy storage systems, effectively spanning the divide between conventional lithium‐ion batteries (LIBs) and supercapacitors. Unfortunately, the energy density of most of Zn‐HSCs has not yet rivalled the levels observed in LIBs. The electrochemical performance of aqueous Zn‐HSCs can be enhanced through the chemical functionalization of graphene‐based cathode materials with thiol moieties as they will be highly suitable for favoring Zn2+ adsorption/desorption. Here, a single‐step reaction is employed to synthesize thiol‐functionalized reduced graphene oxide (rGOSH), incorporating both oxygen functional groups (OFGs) and thiol functionalities, as demonstrated by X‐ray photoelectron spectroscopy (XPS) studies. Electrochemical analysis reveals that rGOSH cathodes exhibit a specific capacitance (540 F g−1) and specific capacity (139 mAh g−1) at 0.1 A g−1 as well as long‐term stability, with over 92% capacitance retention after 10 000 cycles, outperforming chemically reduced graphene oxide (CrGO). Notably, rGOSH electrodes displayed an exceptional maximum energy density of 187.6 Wh kg−1 and power density of 48.6 kW kg−1. Overall, this study offers an unprecedented powerful strategy for the design and optimization of cathode materials, paving the way for efficient and sustainable energy storage solutions to meet the increasing demands of modern energy applications.
MXene confined microcapsules for uremic toxins elimination
Authors: Ye Xiaomin , Yang Chaoyu , Wang Li , Fan Qihui , Shang Luoran , Ye Fangfu
Published: March 2024

Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required. MXene is a promising candidate owning these advantages, yet pristine MXene faces dilemmas including insufficient utility of surface site as well as limited processibility. Here, we develop MXene‐encapsulated porous microcapsules via microfluidics. The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core, by which the microcapsules are endowed with high MXene dosage and remarkable biosafety. Additionally, the MXene nanoflakes assemble into a three‐dimensional network via metal ion‐induced gelation, thereby avoiding restacking and significantly improving surface utilization. Moreover, a freeze‐pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell, which can facilitate the diffusion of the target molecules. These features, combined with additional magneto‐responsiveness rendered by the incorporation of magnetic nanoparticles, contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine, urea, and uric acid. Thus, it is anticipated that the MXene‐encapsulated microcapsules will be promising adsorbents in dialysis‐related applications, and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.
Smart multi‐functional aggregates reoxygenate tumor microenvironment through a two‐pronged strategy to revitalize cancer immunotherapy
Authors: Zhang Yan , Liang Luoqi , Li Hexiang , Cao Yuqing , Meng Du , Li Xinru , Wang Meichen , Wang Jingyuan , Yao Yao , Zhang Shaoqiang , Chen Chao , Hou Peng , Yang Qi
Published: March 2024

PD‐1/PD‐L1 inhibitors have emerged as standard treatments for advanced solid tumors; however, challenges such as a low overall response rate and systemic side effects impede their implementation. Hypoxia drives the remodeling of the tumor microenvironment, which is a leading reason for the failure of immunotherapies. Despite some reported strategies to alleviate hypoxia, their individual limitations constrain further improvements. Herein, a novel two‐pronged strategy is presented to efficiently address hypoxia by simultaneously adopting atovaquone (ATO, inhibiting oxygen consumption) and oxyhemoglobin (HbO2, directly supplementing oxygen) within a multifunctional aggregate termed NPs‐aPD‐1/HbO2/ATO. In addition to eliminating hypoxia with these two components, this smart aggregate also includes albumin and an ROS‐responsive cross‐linker as a controlled release scaffold, along with PD‐1 antibody (aPD‐1) for immunotherapy. Intriguingly, NPs‐aPD‐1/HbO2/ATO demonstrates exceptional tumor targeting in vivo, exhibiting ≈4.2 fold higher accumulation in tumors than in the liver. Consequently, this aggregate not only effectively mitigates hypoxia and significantly assists aPD‐1 immunotherapy but also simultaneously resolves the targeting and systemic toxicity issues associated with individual administration of each component. This study proposes substantial implications for drug‐targeted delivery, addressing tumor hypoxia and advancing immunotherapy, providing valuable insights for advancing cancer treatment strategies.
Hardware for Deep Learning Acceleration
Authors: Song Choongseok , Ye ChangMin , Sim Yonguk , Jeong Doo Seok
Published: March 2024

Deep learning (DL) has proven to be one of the most pivotal components of machine learning given its notable performance in a variety of application domains. Neural networks (NNs) for DL are tailored to specific application domains by varying in their topology and activation nodes. Nevertheless, the major operation type (with the largest computational complexity) is commonly multiply‐accumulate operation irrespective of their topology. Recent trends in DL highlight the evolution of NNs such that they become deeper and larger, and thus their prohibitive computational complexity. To cope with the consequent prohibitive latency for computation, 1) general‐purpose hardware, e.g., central processing units and graphics processing units, has been redesigned, and 2) various DL accelerators have been newly introduced, e.g., neural processing units, and computing‐in‐memory units for deep NN‐based DL, and neuromorphic processors for spiking NN‐based DL. In this review, these accelerators and their pros and cons are overviewed with particular focus on their performance and memory bandwidth.
Synergistic Palladium/Copper‐Catalyzed 1,4‐Difunctionalization of 1,3‐Dienes for Stereodivergent Construction of 1,5‐Nonadjacent Stereocenters
Authors: Wang Hongfa , Zhang Ruiyuan , Zi Weiwei
Published: March 2024

The construction of two distal stereocenters through a single catalytic process is of great interest in organic synthesis. While there are some successful reports regarding stereodivergent preparation of 1,3‐ or 1,4‐stereocenters, the more challenged 1,5‐nonadjacent stereocenters have never been achieved in a stereodivergent fashion. Herein we describe a synergistic palladium/copper catalysis for 1,4‐difunctionalization reactions of 1,3‐dienes, providing access to 1,5‐nonadjacent quaternary stereocenters. Because each of the two catalysts separately controlled one of the newly formed stereocenters, stereodivergent synthesis of all four diastereomers of the products could readily be achieved simply by choosing an appropriate combination of chiral catalysts. Experimental and computational studies supported a mechanism involving a Heck/Tsuji–Trost cascade reaction, and the origins of the stereoselectivity were elucidated.
Recycling of waste wind turbine blades for high‐performance polypropylene composites
Authors: Pu Zhilong , Yang Shuangqiao , Wang Qi
Published: March 2024

Glass fiber‐reinforced epoxy resin composite materials are widely used in various fields because of their excellent properties, especially in the stringent performance requirements of wind turbine blades manufacture for wind power generation. However, the irreversible cross‐linking network of the epoxy resin makes it difficult to recycle. In recent years, the management of large amounts of decommissioned wind turbine blade waste has become spotlight. This study used self‐developed solid‐state shear milling technology to effectively remove the epoxy resin from the glass fiber surface while preserving its high aspect ratio, ensuring its mechanical reinforcement potential. Furthermore, this process also significantly reduced epoxy resin particle size. Subsequently, composites with filler contents up to 50 wt.% were formulated with polypropylene. In the optimized composition, the material exhibited a remarkable 37.1% increase in tensile strength, 147.3% increase in modulus, and 63.8% increase in flexural strength, 165.5% in modulus, respectively. In this research, we conducted a comprehensive exploration into the effects of modifier structure and powder content on different properties of composites, contributing to a deeper understanding of these key factors.
Synthesis of a waterborne epoxy curing agent based on polyether triols and its application in 2K waterborne epoxy coatings
Authors: Lu Zhenhua , Pan Chuncheng , Hou Yong , Zhang Zhaobin , Fu Jiakuan , Li Peng
Published: March 2024

Polyether polyols can improve the performance of waterborne epoxy curing agent. In this paper, intermediates were synthesized from polyether triols with epoxy resin E‐51 and introduced into the epoxy curing agent by reacting with TETA. This paper focuses on the process of synthesizing the intermediates. The 2K waterborne epoxy coating film prepared with polyether triols‐modified waterborne epoxy curing agent exhibits desirable corrosion protection capacity and neutral salt spray resistance up to 600 h. In addition, the 2K waterborne epoxy coating film prepared using the modified waterborne epoxy curing agent with polyether triols displayed improved surface appearance, mechanical properties, and water resistance.
An applicability study on various methods for determining the monomer conversion rate of polyamide 6
Authors: Gao Zhihao , Zhao Renhai , Cai Shunzhong , Ning Xin
Published: March 2024

Anionic ring opening polymerization of ε‐caprolactam (CL) results in the formation of high molecular weight polyamide 6 (PA6) within a few minutes. The monomer conversion rate is an important characterization parameter for polymerization process as well as the end products. This paper used PA6 films with different polymerization degrees as research object for the first time, and systematically compared the performance of four methods for measuring CL conversion rate. The analytical methods were solvent extraction (methanol, ethanol, or water), vacuum removal, thermogravimetric analysis (TGA), and absorbance ratio respectively. For all PA6 products, solvent extraction based on methanol/water and vacuum removal were effective methods for determine their conversion rates. And TGA was only applicable for samples with high degree of polymerization. The CL conversion rate obtained by solvent extraction based on ethanol and absorbance ratio was slightly higher than the real value, especially the latter. Moreover, a new method was discovered and validated during the research process, namely atmospheric devolatilization. The methodology and results in this study can be employed for guiding the production and application of polymers, especially the reactive processing of PA6.
Design of a cofactor self‐sufficient whole‐cell biocatalyst for enzymatic asymmetric reduction via engineered metabolic pathways and multi‐enzyme cascade
Authors: Zou Shuping , Zhang Bing , Han Yuyue , Liu Jinlong , Zhao Kuo , Xue Yaping , Zheng Yuguo
Published: March 2024

NAD(P)H‐dependent oxidoreductases are crucial biocatalysts for synthesizing chiral compounds. Yet, the industrial implementation of enzymatic redox reactions is often hampered by an insufficient supply of expensive nicotinamide cofactors. Here, a cofactor self‐sufficient whole‐cell biocatalyst was developed for the enzymatic asymmetric reduction of 2‐oxo‐4‐[(hydroxy)(‐methyl)phosphinyl] butyric acid (PPO) to L‐phosphinothricin (L‐PPT). The endogenous NADP+ pool was significantly enhanced by regulating Preiss‐Handler pathway toward NAD(H) synthesis and, in the meantime, introducing NAD kinase to phosphorylate NAD(H) toward NADP+. The intracellular NADP(H) concentration displayed a 2.97‐fold increase with the strategy compared with the wild‐type strain. Furthermore, a recombinant multi‐enzyme cascade biocatalytic system was constructed based on the Escherichia coli chassis. In order to balance multi‐enzyme co‐expression levels, the strategy of modulating rate‐limiting enzyme PmGluDH by RBS strengths regulation successfully increased the catalytic efficiency of PPO conversion. Finally, the cofactor self‐sufficient whole‐cell biocatalyst effectively converted 300 mM PPO to L‐PPT in 2 h without the need to add exogenous cofactors, resulting in a 2.3‐fold increase in PPO conversion (%) from 43% to 100%, with a high space‐time yield of 706.2 g L−1 d−1 and 99.9% ee. Overall, this work demonstrates a technological example for constructing a cofactor self‐sufficient system for NADPH‐dependent redox biocatalysis.
Ewing Sarcoma Related protein 1 recognizes R‐loops by binding DNA forks
Authors: Lay Michelle A. , Thompson Valery F. , Adelakun Ajibola D. , Schwartz Jacob C.
Published: March 2024

EWSR1 (Ewing Sarcoma Related protein 1) is an RNA binding protein that is ubiquitously expressed across cell lines and involved in multiple parts of RNA processing, such as transcription, splicing, and mRNA transport. EWSR1 has also been implicated in cellular mechanisms to control formation of R‐loops, a three‐stranded nucleic acid structure consisting of a DNA:RNA hybrid and a displaced single‐stranded DNA strand. Unscheduled R‐loops result in genomic and transcription stress. Loss of function of EWSR1 functions commonly found in Ewing Sarcoma correlates with high abundance of R‐loops. In this study, we investigated the mechanism for EWSR1 to recognize an R‐loop structure specifically. Using electrophoretic mobility shift assays (EMSA), we detected the high affinity binding of EWSR1 to substrates representing components found in R‐loops. EWSR1 specificity could be isolated to the DNA fork region, which transitions between double‐ and single‐stranded DNA. Our data suggests that the Zinc‐finger domain (ZnF) with flanking arginine and glycine rich (RGG) domains provide high affinity binding, while the RNA recognition motif (RRM) with its RGG domains offer improved specificity. This model offers a rational for EWSR1 specificity to encompass a wide range in contexts due to the DNA forks always found with R‐loops.
Measuring the impact of circular economy performance on financial performance: The moderating role of stakeholder engagement
Authors: Esposito Benedetta , Sica Daniela , Supino Stefania , Malandrino Ornella
Published: March 2024

This paper investigates whether and to what extent circular economy performance affects the financial performance of a global sample of listed agri‐food firms. Furthermore, the potential moderating role of stakeholder engagement in empowering this relationship has been tested. A circular economy performance index has been developed based on Environmental Social and Governance scores reclassified in the light of the reuse, reduce, recovery and recycling (4R) paradigm. Then, a multivariate regression model from 2015 to 2022 has been carried out. A broader theoretical framework has been adopted, combining the natural resource‐based view and stakeholder theory. The results show a positive relationship between the circular economy performance, the financial performance and the boosting function played by stakeholder engagement. The study findings provide stimuli for academics and managers to reflect on the profitability of the circular economy and the pivotal role of stakeholder engagement in giving a significant impulse to the circular transition.
Chemical Composition, Repellent, and Phytotoxic Potentials of the Fractionated Resin Essential Oil from Araucaria heterophylla Growing in Tunisia
Authors: Ben Romdhane Oumayma , Baccari Wiem , Saidi Ilyes , Flamini Guido , Ascrizzi Roberta , Chaieb Ikbal , Halim Harrath Abdel , Jannet Hichem Ben
Published: March 2024

The resin essential oil (REO) of the Tunisian Araucaria heterophylla trunk bark was investigated for its chemical composition. Then, it was evaluated for its insecticidal and allelopathic activities. The REO was obtained by hydrodistillation for 9 h (yield of 4.2 % w/w). Moreover, fractional hydrodistillation was carried out at 3‐hour intervals, resulting in 3 fractions (R1–R3), to facilitate chemical identification and localization of the aforementioned biological activities. GC/MS analysis of the obtained samples allowed the identification of 25 compounds, representing between 91.2 and 96.3 % of their total constituents, which consisted predominantly of sesquiterpene hydrocarbons, oxygenated sesquiterpenes and diterpene hydrocarbons. α‐Copaene (10.8 %), γ‐muurolene (5.8 %), α‐copaen‐11‐ol (7.8 %), spathulenol (10.5 %), 15‐copaenol (8.2 %), ylangenal (10.3 %), dehydrosaussurea lactone (7.7 %), and sandaracopimaradiene (11.4 %) were identified as major compounds. The second part aimed to assess the impact of the A. heterophylla EO and its three fractions for their insecticidal and repellent activity against Tribolium castaneum (Herbst), a stored grain pest, of which a strong repellent activity was noted. In addition, the studied samples showed high phytotoxic effects against Lactuca sativa. The third fraction (R3) performed a total inhibitory potential on seed germination and seedling growth of the target plant. Furthermore, alongside this discovery, an estimation was conducted through molecular docking analysis. Wherein the main compounds of the studied samples were docked into the active pocket of protoporphyrinogen IX oxidase (PDB: 1SEZ), a key enzyme in chlorophyll biosynthesis. Thus, it is recommended to use the REO of A. heterophylla as a natural herbicide.
Non‐Oxidative Conversion of Methanol to Dimethyl Ether, Methyl Formate and Dimethoxymethane over Cu/Hβ Catalyst: Tailoring Product Selectivity
Authors: Simitsis Natalia , Mebrahtu Chalachew , Palkovits Regina
Published: March 2024

Herein, we present the production of either dimethyl ether (DME), methyl formate (MF) or dimethoxymethane (DMM), representing pivotal molecules for the green transformation of fuels and chemical industry, by the non‐oxidative gas‐phase conversion of methanol under the same reaction conditions. The product selectivity is optimized by tailoring the acidic and dehydrogenative sites of the bifunctional Cu/Hβ catalyst system by varying the SiO2/Al2O3 ratio of the Hβ zeolite (25 and 520) and the Cu loading (0.5 and 20 wt %). At 240 °C, >99 % (DME), 74.5 % (MF), and 77.3 % (DMM) selectivity is achieved with the respective catalysts 0.5 %Cu/Hβ(25), 20 %Cu/Hβ(520), and 0.5 %Cu/Hβ(520). High acidic site concentration catalyzes DME formation, while the presence of Cu+ species is crucial for DMM formation, and Cu0 species mainly catalyze MF formation. A highly dynamic reaction behaviour is observed, when the dehydrogenative functionality is dominant (i. e., in the production of MF or DMM), presumably due to the dynamic nature of the Cu oxidation state, which is in turn influenced by possible by‐products (H2 and H2O). While the catalytic activity in DME synthesis over 0.5 %Cu/Hβ(25) is remarkably stable over 1500 min TOS, the activity in MF and DMM production over 20 %Cu/Hβ(520) and 0.5 %Cu/Hβ(520), respectively, can be successfully regenerated.
Biocatalytic enantioselective synthesis of cenobamate, an antiepileptic drug
Authors: Haritha Vennapusa , Deepthi Pulivarthi , Gundamalla Rachel , Nagesh Kommu , Satyanarayana Suggala V. , Rao Adari Bhaskar , Balasubramanian Sridhar , Reddy Basireddy Venkata Subba
Published: March 2024

A green and efficient process for the synthesis of cenobamate has been accomplished in 70% yield and >99% ee through the bio‐reduction of β‐ketotetrazole using Daucus carota whole plant cells. The corresponding β‐hydroxytetrazole was isolated in 60% yield and >98% ee. This is the first report on the biocatalytic reduction of β‐ketotetrazole using plant enzymes derived from D. carota root cells with excellent enantioselectivity.
Lc‐Stream: An elastic scheduling strategy with latency constraints in geo‐distributed stream computing environments
Authors: Sun Dawei , Wang Yueru , Sui Jialiang , Gao Shang , Rong Jia , Buyya Rajkumar
Published: March 2024

An effective scheduling strategy is critical for achieving better performance in real‐time stream processing systems. How to quickly and efficiently process real‐time data stream is always challenging, especially when clusters are collaborating in a Geo‐Distributed computing environment. To address these challenges, we propose an elastic scheduling strategy with Latency Constraints in Geo‐Distributed stream computing environments called Lc‐Stream. This article discusses our work from the following aspects: (1) An optimized data stream redirection method that is proposed based on queuing network algorithm, along with a computing resource model, a latency constrained scheduling model and a communication energy consumption model. (2) An updated node selection method based on the inter‐layer task correlation, to reduce the communication latency between groups at the executor granularity. (3) A network cluster distribution for Geo‐Distributed computing environment to ensure energy saving under low transmission latency. Experimental results show that compared to R‐Storm, Lc‐Stream reduces total latency by over 19% and increases throughput by over 37% in typical cross‐domain multi‐task topologies. Compared to Ts‐Stream, Lc‐Stream also reduces total latency by over 15% and increases throughput by over 21%. At the same time, it helps to balance the load among the systems and avoid overuse of compute nodes.
Fluorochrome‐dependent specific changes in spectral profiles using different compensation beads or primary cells in full spectrum cytometry
Authors: Shevchenko Yaroslava , Lurje Isabella , Tacke Frank , Hammerich Linda
Published: March 2024

Full spectrum flow cytometry is a powerful tool for immune monitoring on a single‐cell level and with currently available machines, panels of 40 or more markers per sample are possible. However, with an increased panel size, spectral unmixing issues arise, and appropriate single stain reference controls are required for accurate experimental results and to avoid unmixing errors. In contrast to conventional flow cytometry, full spectrum flow cytometry takes into account even minor differences in spectral signatures and requires the full spectrum of each fluorochrome to be identical in the reference control and the fully stained sample to ensure accurate and reliable results. In general, using the cells of interest is considered optimal, but certain markers may not be expressed at sufficient levels to generate a reliable positive control. In this case, compensation beads show some significant advantages as they bind a consistent amount of antibody independent of its specificity. In this study, we evaluated two types of manufactured compensation beads for use as reference controls for 30 of the most commonly used and commercially available fluorochromes in full spectrum cytometry and compared them to human and murine primary leukocytes. While most fluorochromes show the same spectral profile on beads and cells, we demonstrate that specific fluorochromes show a significantly different spectral profile depending on which type of compensation beads is used, and some fluorochromes should be used on cells exclusively. Here, we provide a list of important considerations when selecting optimal reference controls for full spectrum flow cytometry.
Bakersfield College erases student shortfall by attracting more adult learners
Authors: D’Orio Wayne
Published: March 2024

When COVID‐19 reduced the enrollment at California's Bakersfield College by 14% in just two years, Dr. Brian A. Rodríguez knew his job would be more important than ever.