bluuebunny/crossref_metadata_2025 huggingface dataset:
Water‐Soluble Organic Nanoparticles with Programable Intermolecular Charge Transfer for NIR‐II Photothermal Anti‐Bacterial Therapy
Authors: Tian Shuang , Bai Haotian , Li Shengliang , Xiao Yafang , Cui Xiao , Li Xiaozhen , Tan Jihua , Huang Zhongming , Shen Dong , Liu Weimin , Wang Pengfei , Tang Ben Zhong , Lee Chun‐Sing
Published: March 2021

Extensive recent efforts have been put on the design of high‐performance organic near‐infrared (NIR) photothermal agents (PTAs), especially over NIR‐II bio‐window (1000–1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR‐II response. Here, we report organic nanoparticles of intermolecular charge‐transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR‐I to NIR‐II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red‐shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram‐negative and Gram‐positive bacteria. This work opens a new avenue into the development of efficient PTAs.
“Host in Host” Supramolecular Core–Shell Type Systems Based on Giant Ring‐Shaped Polyoxometalates
Authors: Falaise Clément , Khlifi Soumaya , Bauduin Pierre , Schmid Philipp , Shepard William , Ivanov Anton A. , Sokolov Maxim N. , Shestopalov Michael A. , Abramov Pavel A. , Cordier Stéphane , Marrot Jérôme , Haouas Mohamed , Cadot Emmanuel
Published: March 2021

Herein, we show how the chaotropic effect arising from reduced molybdate ions in acidified aqueous solution is able to amplify drastically weak supramolecular interactions. Time‐resolved Small Angle X‐ray Scattering (SAXS) analysis suggests that molybdenum‐blue oligomeric species form huge aggregates in the presence of γ‐cyclodextrin (γ‐CD) which results in the fast formation of nanoscopic {Mo154}‐based host‐guest species, while X‐ray diffraction analysis reveals that the ending‐point of the scenario results in an unprecedented three‐component well‐ordered core–shell‐like motif. A similar arrangement was found by using preformed hexarhenium chalcogenide‐type cluster [Re6Te8(CN)6]4− as exogenous guest. This seminal work brings better understanding of the self‐assembly processes in general and gives new opportunities for practical applications in the design of complex multicomponent materials via the simplicity of the non‐covalent chemistry.
Unravelling the Fast Alkali‐Ion Dynamics in Paramagnetic Battery Materials Combined with NMR and Deep‐Potential Molecular Dynamics Simulation
Authors: Lin Min , Liu Xiangsi , Xiang Yuxuan , Wang Feng , Liu Yunpei , Fu Riqiang , Cheng Jun , Yang Yong
Published: March 2021

Solid‐state nuclear magnetic resonance (ssNMR) has received extensive attention in characterizing alkali‐ion battery materials because it is highly sensitive for probing the local environment and dynamic information of atoms/ions. However, precise spectral assignment cannot be carried out by conventional DFT for high‐rate battery materials at room temperature. Herein, combining DFT calculation of paramagnetic shift and deep potential molecular dynamics (DPMD) simulation to achieve the converged Na+ distribution at hundreds of nanoseconds, we obtain the statistically averaged paramagnetic shift, which is in excellent agreement with ssNMR measurements. Two 23Na shifts induced by different stacking sequences of transition metal layers are revealed in the fast chemically exchanged NMR spectra of P2‐type Na2/3(Mg1/3Mn2/3)O2 for the first time. This DPMD simulation auxiliary protocol can be beneficial to a wide range of ssNMR analysis in fast chemically exchanged material systems.
Novel Lamellar Tetrapotassium Pyromellitic Organic for Robust High‐Capacity Potassium Storage
Authors: Pan Qingguang , Zheng Yongping , Tong Zhaopeng , Shi Lei , Tang Yongbing
Published: March 2021

Redox‐active organics are investigation hotspots for metal ion storage due to their structural diversity and redox reversibility. However, they are plagued by limited storage capacity, sluggish ion diffusion kinetics, and weak structural stability, especially for K+ ion storage. Herein, we firstly reported the lamellar tetrapotassium pyromellitic (K4PM) with four active sites and large interlayer distance for K+ ion storage based on a design strategy, where organics are constructed with the small molecular mass, multiple active sites, fast ion diffusion channels, and rigid conjugated π bonds. The K4PM electrode delivers a high capacity up to 292 mAh g−1 at 50 mA g−1, among the best reported organics for K+ ion storage. Especially, it achieves an excellent rate capacity and long‐term cycling stability with a capacity retention of ≈83 % after 1000 cycles. Incorporating in situ and ex‐situ techniques, the K+ ion storage mechanism is revealed, where conjugated carboxyls are reversibly rearranged into enolates to stably store K+ ions. This work sheds light on the rational design and optimization of organic electrodes for efficient metal ion storage.
Tough and self‐healing hydrophobic association hydrogels with cationic surfactant
Authors: Zhao Zhen , Bai Yingrui , Sun Jinsheng , Lv Kaihe , Lei Shaofei , Qiu Jiaxian
Published: March 2021

Hydrophobic association (HA) hydrogels with outstanding mechanical, rheological and recovery properties were successfully synthesized by micellar copolymerization of acrylamide with lauryl methacrylate. The synthesis occurred at room temperature and the synthesis condition was moderate by using the redox initiator system of Ammonium persulfate ‐ sodium bisulfite as initiators. Cationic surfactant (dodecyl trimethyl ammonium bromide) was utilized to form micelles with hydrophobe, served as physical cross‐linking points in the 3D networks of hydrogels. The HA hydrogels showed a high tensile strength of 181 kPa, superior stretchability of 2300% and excellent toughness of 2.16 MJ m−3. Moreover, they owned extraordinary self‐recovery under different conditions. It is hopeful that the hydrogels with superior mechanical strength and self‐healing properties would be applied to the fields of biomedicine and engineering. Meanwhile, based on above materials, HA hydrogels could also be synthesized with the combination of hydrophobic association and other synergistic effects, such as latex particles, electrostatic effect and nanoparticles.
Applications of Carbon Dots (CDs) in Latent Fingerprints Imaging
Authors: Shabashini Arivalagan , Panja Sumit Kumar , Nandi Ganesh Chandra
Published: March 2021

Carbon dots (CDs), a new member of the carbon‐based material family, possess unique properties, such as high fluorescence, non‐toxicity, eco‐friendliness, stability and cost‐effectiveness. These properties helped CDs to receive tremendous attention in various fields, namely, biological, opto‐electronic, bio‐imaging and energy‐related applications. Although CDs are widely explored in bio‐imaging and bio‐sensing applications, their effectiveness in forensic science and technology is comparatively new. In this review, applications of CDs pertaining to latent FPs recovery since 2015 to 2020 is summarized comprehensively.
Socrative, a powerful digital tool for enriching the teaching–learning process and promoting interactive learning in Chemistry and Chemical Engineering studies
Authors: Roman Claudia , Delgado Miguel A. , García‐Morales Moisés
Published: March 2021

Mobile learning is an emerging educational methodology that requires an updated conceptualization to yield effective pedagogical approaches that may enrich the teaching–learning processes. The present research aimed to better understand and to assess the effectiveness of mobile learning in Science and Engineering Higher Education settings. The experience was carried out over two consecutive academic years, 2018–2019 and 2019–2020, in a Polymer Technology course taught in Chemistry and Chemical Engineering Bachelor programs. The “Socrative” online mobile platform enabled to conduct formative assessment through the use of multiple choice quizzes that were meticulously designed to facilitate understanding and to provide instant feedback. A three‐way analysis of variance hypothesis test allowed concluding that Socrative had a significant effect, at the 0.05 level, on improving the students’ average grade (about 1.5 points higher, on a scale of 0–10) in practical lab sessions as compared with a control group that did not participate in this type of methodology. Moreover, the results from an opinion survey revealed that Socrative enabled to achieve a meaningful learning of the fundamentals, made the everyday classrooms more engaging and fun, increased motivation, and, in general, helped create a more pleasant learning environment. The use of Socrative as an effective instrument that allowed minimizing learning disruptions as a consequence of the recent COVID‐19 outbreak is also reported.
Learn how you can support campus diversity while staying legally compliant
Authors: Dalessandro Dina
Published: March 2021

In the wake of last year's Black Lives Matter protests, many institutions made promises to increase support, representation, and funding for underrepresented students of color. But when seeking to implement, develop, and fundraise such measures, many remain unsure how to do so in a legally compliant manner.
Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors
Authors: Sander Michael S. , Stukalin Igor , Vallerand Isabelle A. , Goutam Siddhartha , Ewanchuk Benjamin W. , Meyers Daniel E. , Pabani Aliyah , Morris Don G. , Heng Daniel Y. C. , Cheng Tina
Published: March 2021

Background

Metastatic uveal melanoma (MUM) is associated with poor survival and inferior response to immune checkpoint inhibitor (ICI) therapy when compared with metastatic cutaneous melanoma. Currently, prognostic biomarkers are lacking to guide treatment decisions.

Patients and Methods

We conducted a multicenter, retrospective cohort study using a centralized, province‐wide cancer database in Alberta, Canada. We identified 37 patients with histologically confirmed MUM who received at least one dose of single‐agent pembrolizumab or nivolumab, or combination therapy nivolumab and ipilimumab. A modified immune prognostic index (IPI), based on the previously reported lung immune prognostic index, was used to stratify patients into favorable and poor IPI groups. Survival analyses were conducted using the Kaplan–Meier method and Cox proportional hazards models, adjusting for baseline age (≥60) and ECOG performance status, to assess the associations between IPI and overall survival (OS). Time to treatment failure (TTF) was also assessed using the Kaplan–Meier method. The association between IPI and objective response rate was examined using chi‐squared tests. Logistic regression was used to determine the association between IPI and immune‐related adverse events (irAEs).

Results

Median OS was 15.6 (range 0.6–57.6) months with 45.9% 1‐year survival rate at a median follow‐up of 11.8 months. We found that a favorable IPI was significantly associated with OS [median 30.5 (12.0‐not reached) months in the favorable IPI group compared with 4.6 (2.1–16.0) months in the poor IPI group (p = 0.001)] (HR=4.81, 95% CI; 1.64–14.10, p = 0.004), TTF [median 5.1 (95% CI; 2.1–10.4) months in the favorable IPI group compared with 3.7 (95% CI; 1.4–6.4) months in the poor IPI group (p = 0.0191)], and irAE (HR=6.67, 95% CI; 1.32–33.69, p = 0.0220).

Conclusions

The modified IPI may be a useful tool in clinical practice for identifying MUM patients who are more likely to experience irAEs and realize a survival benefit from ICI treatment.
Review guidance for complying with the NCAA's sexual violence prevention attestation requirements
Authors: McCarthy Claudine
Published: March 2021

It's that time of year again for NCAA member schools to complete the NCAA's annual campus sexual violence prevention attestation requirements process. To help ensure that your athletics department is in compliance with the NCAA's policy, you'll want to review this guidance from Jen Jacobson, Director of Sexual Violence Prevention Education at Macalester College in Minnesota, who gave a presentation during the 2021 virtual NCAA Convention.
Keep mental, physical health ‘front and center’
Authors: McCarthy Claudine
Published: March 2021

Through the unknowns of the COVID‐19 pandemic, Earl Hilton, M.P.A., J.D., Director of Athletics at North Carolina A&T State University, strives to keep the mental and physical health and safety of student‐athletes and staff “front and center,” more so now than ever.
The effects of oxygen–ozone therapy on regulatory T‐cell responses in multiple sclerosis patients
Authors: Tahmasebi Safa , Qasim Maytham T. , Krivenkova Maria V. , Zekiy Angelina O. , Thangavelu Lakshmi , Aravindhan Surendar , Izadi Morteza , Jadidi‐Niaragh Farhad , Ghaebi Mahnaz , Aslani Saeed , Aghebat‐Maleki Leili , Ahmadi Majid , Roshangar Leila
Published: March 2021

Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing‐remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell‐related factors (FoxP3, IL‐10, TGF‐β, miR‐17, miR‐27, and miR‐146A), and the secretion levels of IL‐10 and TGF‐β were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR‐17 and miR‐27), IL‐10, and TGF‐β factors in patients after oxygen–ozone (O2‐O3) therapy compared to before treatment. In contrast, oxygen–ozone therapy notably decreased the expression level of miR‐146a in treated patients. Interestingly, the secretion levels of both IL‐10 and TGF‐β cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen–ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen–ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.
Valproic acid protects intestinal organoids against radiation via NOTCH signaling
Authors: Park Misun , Kwon Junhye , Youk Heejeong , Shin Ui Sup , Han Young‐Hoon , Kim Younjoo
Published: March 2021

Radiotherapy is a leading treatment for various types of cancer. However, exposure to high‐dose ionizing radiation causes acute gastrointestinal injury and gastrointestinal syndrome. This has significant implications for human health, and therefore, radioprotection is a major area of research. Radiation induces the loss of intestinal stem cells; hence, the protection of stem cells expressing LGR5 (a marker of intestinal epithelial stem cells) is a key strategy for the prevention of radiation‐induced injury. In this study, we identified valproic acid (VPA) as a potent radioprotector using an intestinal organoid culture system. VPA treatment increased the number of LGR5+ stem cells and organoid regeneration after irradiation. N‐[N‐(3,5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butyl ester (DAPT, an inhibitor of NOTCH signaling) blocked the radioprotective effects of VPA, indicating that NOTCH signaling is a likely mechanism underlying the observed effects of VPA. In addition, VPA acted as a radiosensitizer via the inhibition of histone deacetylase (HDAC) in a colorectal cancer organoid. These results demonstrate that VPA exerts strong protective effects on LGR5+ stem cells via NOTCH signaling and that the inhibition of NOTCH signaling reduces these protective effects, providing a basis for the improved management of radiation injury.
E3 ubiquitin ligase TRIM24 deficiency promotes NLRP3/caspase‐1/IL‐1β‐mediated pyroptosis in endometriosis
Authors: Hang Yuanyuan , Tan Li , Chen Qiong , Liu Qiaoli , Jin Yuli
Published: March 2021

Endometriosis is an inflammation‐dependent disease that shares similarities with malignant tumors including attachment and infiltration. Tripartite motif‐containing 24 (TRIM24) has been illustrated in inflammatory responses and gynecological tumors, and Nod‐like receptor protein 3 (NLRP3) inflammasome has been implicated in endometriosis. However, the involvement of TRIM24 and the role of NLRP3/caspase‐1/interleukin‐1β (IL‐1β)‐mediated pyroptosis in endometriosis remain obscure. In this study, we originally detected the decreased expression of TRIM24 in the ectopic endometrium of endometriosis compared with the normal endometrium. Then we measured the promoted protein expression of pyroptotic biomarkers (NLRP3, procaspase‐1, caspase‐1, pro‐IL‐1β, and IL‐1β) using Western blot analysis and the stimulated secretion of IL‐1β and IL‐18 by enzyme‐linked immunosorbent assay in ectopic human endometrial stromal cells (hESC) compared with normal hESC. TRIM24‐small‐interfering RNA (siTRIM24) was used to silence TRIM24, whereas TRIM24‐pcDNA3.1 was used for overexpressing TRIM24. The migration of hESC was determined by a Transwell migration assay. Coimmunoprecipitation and ubiquitination analyses were conducted to explore the interaction between TRIM24 and NLRP3. Subsequently, we found that TRIM24 negatively regulated NLRP3/caspase‐1/IL‐1β‐mediated pyroptosis and cell migration of hESC, and CY‐09, the specific inhibitor of NLRP3, could reverse the promoted pyroptosis and cell migration induced by siTRIM24. Furthermore, TRIM24 interacted with NLRP3 and the upregulation of TRIM24 facilitated the ubiquitination of NLRP3 in ectopic hESC. Our findings suggest that TRIM24 may participate in the progression of endometriosis through the NLRP3/caspase‐1/IL‐1β‐mediated pyroptotic pathway via ubiquitination of NLRP3, which reveals the significant molecular mechanism underlying endometriosis.
Synthesis of Triphenylethylene‐Naphthalimide Conjugates as topoisomerase‐IIα inhibitor and HSA binder
Authors: Rani Sudesh , Luxami Vijay , Paul Kamaldeep
Published: March 2021

A series of triphenylethylene‐naphthalimide (TPE‐naph) conjugates was synthesized by a molecular hybridization technique, and their anticancer activity was evaluated in vitro on 60 human cancer cell lines through their cytotoxicity. The ratios of E and Z isomers were determined on the basis of HPLC methodology and NMR spectroscopy. The structure‐activity relationship for anticancer activity was deduced on the basis of the nature and bulkiness of the amine attached to the C‐4 position of the naphthalene ring. Experimental and molecular modeling studies of the most active TPE‐naph conjugate bearing a morpholinyl group showed that it was able to inhibit topoisomerase‐II (TOPO‐II) as a possible intracellular target. Moreover, the transportation behavior of TPE‐naph conjugate towards human serum albumin (HSA) indicated efficient binding affinity. The steady‐state and time‐dependent fluorescent results suggested that this conjugate quenched HSA significantly through static as well as dynamic quenching. Thus, this report discloses the scope of triphenylethylene‐naphthalimide (TPE‐naph) conjugates as efficient anticancer agents.
Optimized load balancing in high‐performance computing for big data analytics
Authors: Mirtaheri Seyedeh Leili , Grandinetti Lucio
Published: March 2021

New generation application problems in big data and high‐performance computing (HPC) areas claim very diverse operational properties. The convergence requires the dynamic behavior of system components. Load balancing is a critical issue in response to the highly unpredictable, dynamic, and data‐oriented behavior of the system. Possible practical constraints such as communication and load transfer delays play an essential role in designing a dynamic load balancer. On the other hand, according to most of the new platforms' distributed nature, the load balancer should be able to perform in a fully distributed manner. In this research, we consider practical issues, including different processing power, storage capability, communication, load transfer delays, and propose two distributed and optimized load balancing methods in HPC for Big Data processing. We model the constraints and present an argument named compensating factor for the optimized load balancer. We try to minimize the task execution time by reducing the nodes' idle time. We evaluate the proposed methods in different scenarios by using Monte Carlo. Evaluations results show that proposed methods decrease idle time significantly while being scalable to network size and applicable in heterogeneous networks with dynamic resources and configuration.
A graphical processing unit‐based parallel hybrid genetic algorithm for resource‐constrained multi‐project scheduling problem
Authors: Uysal Furkan , Sonmez Rifat , Isleyen Selcuk Kursat
Published: March 2021

In this article, we present a parallel graphical processing unit (GPU)‐based genetic algorithm (GA) for solving the resource‐constrained multi‐project scheduling problem (RCMPSP). We assumed that activity pre‐emption is not allowed. Problem is modeled in a portfolio of projects where precedence and resource constraints affect the portfolio duration. We also assume that the durations, availability of resources are deterministic and portfolio has a static nature. The objective in this article is to find a start time for each activity of the project so that the portfolio duration is minimized, while satisfying precedence relations and resource availabilities within a reasonable amount of time for small and large problem instances. In order to compare the efficiency of the proposed parallel GPU‐based GA, problem is solved together with a CPU and a GPU. The results showed that GPU‐based parallel GA has high potential for improving the performance of GAs for the RCMPSP particularly, for large‐scale problems.
Analysis and design of a low jitter delay‐locked loop using lock state detector
Authors: Modanlou Shahram , Ardeshir Gholamreza , Gholami Mohammad
Published: March 2021

In this paper, a technique is proposed to improve the jitter performance of a delay‐locked loop (DLL). The DLL is structured by charge pump (CP), phase detector (PD), voltage control delay line (VCDL) and the reference clock. The jitter generated by each part of DLL is separately studied, and a closed‐form equation is extracted. This closed‐form equation shows that the jitter generated by CP, PD and the secondary jitter of the reference clock and VCDL is applied to output by the control voltage. A jitter improving circuit is used to cancel the jitter of the control voltage. To verify the closed‐form equation, the DLL is designed in 0.18 μm CMOS technology with the proposed technique to improve the output jitter. The simulated root‐mean‐square and peak‐to‐peak jitters are 2.12 and 4.37 ps at 250 MHz, respectively. The power dissipation at 250 MHz is 2.78 mW for a supply voltage of 1.2 V.
Human Infection Challenge Experiments: Then and Now
Authors: Miller Franklin G. , Moreno Jonathan D.
Published: March 2021

In the midst of the Covid‐19 pandemic, ethicists, researchers, and journalists have recommended studies that deliberately infect healthy volunteers with the coronavirus as a scientific means of expediting vaccine development. In this essay, we trace the history of infection challenge experiments and reflect on the Nuremberg Code of 1947, issued in response to brutal human experiments conducted by Nazi investigators in concentration camps. We argue that the Code continues to offer valuable guidance for assessing the ethics of this controversial form of research, with respect particularly to the acceptable limits to research risks and the social value of research necessary to justify exposing human participants to these risks.
Isolated reefs support stable fish communities with high abundances of regionally fished species
Authors: Birt Matthew J. , Cure Katherine , Wilson Shaun , Newman Stephen J. , Harvey Euan S. , Meekan Mark , Speed Conrad , Heyward Andrew , Goetze Jordan , Gilmour James
Published: March 2021

Anthropogenic impacts at isolated and inaccessible reefs are often minimal, offering rare opportunities to observe fish assemblages in a relatively undisturbed state. The remote Rowley Shoals are regarded as one of the healthiest reef systems in the Indian Ocean with demonstrated resilience to natural disturbance, no permanent human population nearby, low visitation rates, and large protected areas where fishing prohibitions are enforced. We used baited remote underwater video systems (BRUVS) to quantify fish assemblages and the relative abundance of regionally fished species within the lagoon, on the slope and in the mesophotic habitat at the Rowley Shoals at three times spanning 14 years and compared abundances of regionally fished species and the length distributions of predatory species to other isolated reefs in the northeast Indian Ocean. Fish assemblage composition and the relative abundance of regionally fished species were remarkably stable through time. We recorded high abundances of regionally fished species relative to other isolated reefs, including globally threatened humphead Maori wrasse (Cheilinus undulatus) and bumphead parrotfish (Bolbometopon muricatum). Length distributions of fish differed among habitats at the Rowley Shoals, suggesting differences in ontogenetic shifts among species. The Cocos (Keeling) Islands typically had larger‐bodied predatory species than at the Rowley Shoals. Differences in geomorphology, lagoonal habitats, and fishing history likely contribute to the differences among remote reefs. Rowley Shoals is a rare example of a reef system demonstrating ecological stability in reef fish assemblages during a time of unprecedented degradation of coral reefs.
A machine learning risk score predicts mortality across the spectrum of left ventricular ejection fraction
Authors: Greenberg Barry , Adler Eric , Campagnari Claudio , Yagil Avi
Published: March 2021

Aims

Heart failure (HF) guideline recommendations categorize patients according to left ventricular ejection (LVEF). Mortality risk, however, varies considerably within each category and the likelihood of death in an individual patient is often uncertain. Accurate assessment of mortality risk is an important component in the decision‐making process for many therapies. In this report, we assess the accuracy of MARKER‐HF, a recently described machine learning‐based risk score, in predicting mortality of patients in the three guideline‐defined HF categories and its ability to distinguish risk of death for patients within each category.

Methods and results

MARKER‐HF was used to calculate mortality risk in a hospital‐based cohort of 4064 patients categorized into groups with reduced, mid‐range, or preserved LVEF. MARKER‐HF was substantially more accurate than LVEF in predicting mortality and was highly accurate in all three HF categories, with c‐statistics ranging between 0.83 to 0.89. Moreover, MARKER‐HF accurately discriminated between patients at high, intermediate and low levels of mortality risk within each of the three categories of HF used by guidelines.

Conclusions

MARKER‐HF accurately predicts mortality in patients within the three categories of HF used in guidelines for management recommendations and it discriminates between magnitude of risk of patients in each category. MARKER‐HF mortality risk prediction should be helpful to providers in making recommendations regarding the advisability of therapies designed to mitigate this risk, particularly when they are costly or associated with adverse events, and for patients and their families in making future plans.
Construction of Isomorphous Coordination Polymers with 2‐(3‐(pyridin‐2‐yl)‐1H‐pyrazol‐1‐yl) acetate Ligand: Structures, Fluorescent Temperature Sensing, and Magnetic Properties
Authors: Shen Chenhu , Xie Yibing , Kong Bingshan , Ma Jing‐xin , Yang Jinhui
Published: March 2021

In this work, four isomorphous two‐dimensional (2D) complexes, [M(PPA)(HCOO)]n (M=Zn (1), Co (2), Ni (3) and Cd (4)) have been synthesized under solvothermal conditions by mixed 2‐(3‐(pyridin‐2‐yl)‐1H‐pyrazol‐1‐yl) acetate (PPA) with transition metal ion (Zn2+, Co2+, Ni2+ or Cd2+). Single‐crystal and powder X‐ray diffraction show that the four complexes are isomorphous. Due to different electronic configurations for Zn2+, Co2+, Ni2+, and Cd2+, the solid‐state fluorescence properties of 1 and 4, and the temperature dependence of magnetic susceptibility of 2 and 3 were investigated, respectively. The results show that 1 and 4 have obvious blue light emission at the range of 310 to 430 nm with 1.37 % of the quantum yield and 3.80 ns of the lifetime for 1 and 1.67 % and 2.43 ns for 4, respectively. Notably, the intensity‐based fluorescent temperature sensing reveals that both of them can be used as luminescent thermometers. Magnetic investigation of 2 and 3 reveals that strong antiferromagnetic interactions exist within the paramagnetic centers, Co(II) or Ni(II), with −29.09 K of Weiss constant for 2 and −64.02 K for 3, respectively.
Selective and Additive‐Free Hydrogenation of Nitroarenes Mediated by a DMSO‐Tagged Molecular Cobalt Corrole Catalyst
Authors: Timelthaler Daniel , Schöfberger Wolfgang , Topf Christoph
Published: March 2021

We report on the first cobalt corrole that effectively mediates the homogeneous hydrogenation of structurally diverse nitroarenes to afford the corresponding amines. The given catalyst is easily assembled prior to use from 4‐tert‐butylbenzaldehyde and pyrrole followed by metalation of the resulting corrole macrocycle with cobalt(II) acetate. The thus‐prepared complex is self‐contained in that the hydrogenation protocol is free from the requirement for adding any auxiliary reagent to elicit the catalytic activity of the applied metal complex. Moreover, a containment system is not required for the assembly of the hydrogenation reaction set‐up as both the autoclave and the reaction vessels are readily charged under a regular laboratory atmosphere.
Chemoselective Deoxygenation of 2° Benzylic Alcohols through a Sequence of Formylation and B(C6F5)3‐Catalyzed Reduction
Authors: Richter Sven C. , Oestreich Martin
Published: March 2021

A sequence of formylation and B(C6F5)3‐catalyzed reduction of the resulting formate with Et3SiH enables the chemoselective deoxygenation of secondary benzylic alcohols. Primary benzylic and tertiary non‐benzylic alcohols are not reduced by this protocol. The formyl group fulfills a double role as activator and self‐sacrificing protecting group. The deoxygenation of these formates is fast and can be carried out in the presence of other potentially reducible groups. Neighboring‐group participation was found in the deoxygenation of certain diol motifs.
Biocatalytic Approaches to the Enantiomers of Wieland–Miescher Ketone and its Derivatives
Authors: Bertuletti Susanna , Bayout Ikram , Bassanini Ivan , Ferrandi Erica E. , Bouzemi Nassima , Monti Daniela , Riva Sergio
Published: March 2021

Biocatalytic approaches have been investigated in order to isolate the enantiomers of Wieland–Miescher ketone (1) and of its alcoholic derivatives (cis‐2 and trans‐3). Specifically, two enzymes from our in‐house metagenomic collection of oxidoreductases, IS2‐SDR and Dm7α‐HSDH, catalyzed the kinetic resolution of the starting racemic ketone 1 or its complete conversion into two diastereomeric products, respectively. Moreover, the kinetic resolution of the racemic cis‐alcohol (2) was very efficiently obtained (E≅2.000) by lipase PS catalyzed acetylation in dry acetone. All the products were isolated with ee≥95 %. Simple chemical elaborations of some of them allowed to isolate the missing enantiomers.
A Diversity‐Oriented Approach to Large Libraries of Artificial Macrocycles
Authors: Kharchenko Serhii H. , Iampolska Anna D. , Radchenko Dmytro S. , Vashchenko Bohdan V. , Voitenko Zoia V. , Grygorenko Oleksandr O.
Published: March 2021

Diversity‐oriented approach to large artificial macrocycle libraries with a ring size of 13—18 atoms relying on the “build‐couple‐pair” strategy is disclosed. The “couple” phase included three one‐pot steps including consequent amide coupling of N‐Boc‐monoprotected vicinal diamines with two alkenyl carboxylic acids, followed by ring‐closing metathesis as the key “pair” step. The scope and limitations of the method were established for all three reagents. In particular, various acyclic, mono‐ and bicyclic aliphatic diamine derivatives with the N−C−C−N dihedral angle less than ca. 130° appeared to be suitable substrates. The proposed approach was used to construct a virtual library of 1.8 ⋅ 105 macrocycles derived from 12,283 different scaffolds. More than 40 % of members of this library contained a protected amino function and hence can be suitable for the post‐pairing modification, thus giving rise to at least a billion‐size chemical space based on the REAL‐type synthetic methodology. Validation of the approach under parallel synthesis conditions on a 383‐member subset showed a 61 % success rate over the whole 4–5‐step reaction sequence. Finally, the synthetic approach also worked on a gram scale (up to 8.0 g).
A General Stereocontrolled Synthesis of Opines through Asymmetric Pd‐Catalyzed N‐Allylation of Amino Acid Esters
Authors: Albat Dominik , Neudörfl Jörg‐Martin , Schmalz Hans‐Günther
Published: March 2021

A stereo‐divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium‐catalyzed N‐allylation of α‐amino acid esters (up to 97 % ee or 99 : 1 d.r.) using methyl (E)‐2‐penten‐4‐yl carbonate in the presence of only 1 mol% of a catalyst, prepared in‐situ from the C2‐symmetric diphosphine iPr‐MediPhos and [Pd(allyl)Cl]2. Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N‐allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N‐Boc‐protection.
Fabrication of Electrochemical Immunosensor for Detection of Interleukin 8 Biomarker via Layer‐by‐layer Self‐assembly Process on Cost‐effective Fluorine Tin Oxide Electrode
Authors: Aydın Elif Burcu , Sezgintürk Mustafa Kemal
Published: March 2021

A highly sensitive impedimetric immunosensor for the determination of interleukin 8 (IL 8) cancer biomarker was fabricated via simple fabrication process. A silane agent with isocyanate groups, 3‐(triethoxysilyl)propyl isocyanate (IPTES), were utilized for binding of IL 8 antigen specific antibodies and self‐assembled on the fluorine tin oxide (FTO) substrate with a standard silanization chemistry. Under optimum experimental conditions, the designed immunosensor had a wide linear detection range of 0.02–4 pg/mL, a low limit of detection of 11.9 fg/mL and a high sensitivity of 4.42 kΩ pg−1 mL cm−2. The designed biosensor displayed high reproducibility and repeatability, good selectivity against interference biomarkers.
Physicochemical properties and microstructure of corn flour–cellulose fiber extrudates
Authors: Zhao Yilin , Zhao Chengbin , Tang Xudong , Zhou Jingyi , Li Hao , Zhang Hao , Liu Jingsheng
Published: March 2021

In this study, corn flour with 24% w/w moisture content was extruded, and cellulose at varied weight ratios was added in order to investigate its effect on the extrudate's physicochemical properties. Twin‐screw extrusion was divided into five temperature zones, and the screw temperature profile was 60℃, 120℃, 140℃, 120℃, and 110℃, respectively, and screw speed was 150 rpm. The cellulose content was 1%–15% w/w. Results showed that the addition of cellulose led to an increase in hardness, L* and b* of the extruded samples, and a decrease in degree of expansion, a*, thermal enthalpy of the sample paste. The sample paste exhibited a solid‐like characteristic. Microscopic morphology analysis showed that surface wrinkles of the sample increased with the increase of cellulose addition. The addition of cellulose can effectively increase the degree of puffing of corn flour–cellulose fiber extrudates.
Neuropsychiatric symptoms and the outcome of cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging
Authors: Krell‐Roesch Janina , Syrjanen Jeremy A. , Machulda Mary M. , Christianson Teresa J. , Kremers Walter K. , Mielke Michelle M. , Knopman David S. , Petersen Ronald C. , Vassilaki Maria , Geda Yonas E.
Published: March 2021

Objective

Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. We examined associations between NPS and the outcomes of global and domain‐specific cognitive trajectories.

Methods

In this longitudinal study conducted in the setting of the population‐based Mayo Clinic Study of Aging, 5081 community‐dwelling, nondemented individuals aged ≥50 years (51% males) underwent NPS assessment using Neuropsychiatric Inventory Questionnaire (NPI‐Q), and Beck Depression and Anxiety Inventories (BDI‐II, BAI). Global and domain‐specific (memory, language, attention, and visuospatial skills) cognitive performance was assessed through neuropsychological testing every 15 months. Associations between baseline NPS and trajectories for individual yearly change in cognitive z‐scores were calculated using linear mixed‐effect models.

Results

Cognition declined regardless of NPS status over the median follow‐up of 4.5 years. Presence of NPS was associated with increased cognitive decline. Differences in annualized change in global cognition z‐scores for participants with NPS compared to without NPS ranged from −0.018 (95% CI −0.032, −0.004; p = 0.011) for irritability to −0.159 (−0.254, −0.065; p = 0.001) for hallucinations. Associations between NPS and annual decline in global cognition were significant for most NPI‐Q‐assessed NPS and clinical depression (BDI‐II≥13). Participants with NPI‐Q‐assessed depression, apathy, nighttime behavior, and clinical depression had greater decline in all domain‐specific z‐scores; presence of delusions and anxiety was associated with more pronounced decline in language, attention and visuospatial skills.

Conclusion

NPS were associated with a more accelerated cognitive decline. Clinical assessment and potential treatment of NPS is warranted even in a community setting as NPS may impact cognitive decline in nondemented individuals.
Insertion Mutation in Tnfrsf11a Causes a Paget's Disease–Like Phenotype in Heterozygous Mice and Osteopetrosis in Homozygous Mice
Authors: Alonso Nerea , Wani Sachin , Rose Lorraine , van't Hof Rob J. , Ralston Stuart H. , Albagha Omar M.E.
Published: March 2021

Early onset familial Paget's disease of bone (EoPDB), familial expansile osteolysis, and expansile skeletal hyperphosphatasia are related disorders caused by insertion mutations in exon 1 of the TNFRSF11A gene, which encodes receptor activator of nuclear factor κB (RANK) protein. To understand the mechanisms underlying these disorders, we developed a mouse model carrying the 75dup27 mutation which causes EoPDB. Mice heterozygous for the mutation (Tnfrsf11a75dup27/−) developed a PDB-like disorder with focal osteolytic lesions in the hind limbs with increasing age. Treatment of these mice with zoledronic acid completely prevented the development of lesions. Studies in vitro showed that RANK ligand (RANKL)-induced osteoclast formation and signaling was impaired in bone marrow cells from Tnfrsf11a75dup27/− animals, but that osteoclast survival was increased independent of RANKL stimulation. Surprisingly, Tnfrsf11a75dup27/75dup27 homozygotes had osteopetrosis at birth, with complete absence of osteoclasts. Bone marrow cells from these mice failed to form osteoclasts in response to RANKL and macrophage colony-stimulating factor (M-CSF) stimulation. This intriguing study has shown that in heterozygous form, the 75dup27 mutation causes focal osteolytic lesions in vivo reminiscent of the human disorder and extends osteoclast survival independently of RANKL signaling. In homozygous form, however, the mutation causes osteopetrosis due to failure of osteoclast formation and insensitivity to RANKL stimulation. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
Piperlongumine attenuates oxidative stress, inflammatory, and apoptosis through modulating the GLUT‐2/4 and AKT signaling pathway in streptozotocin‐induced diabetic rats
Authors: Xu Ping , Xiao Juan , Chi Shuixia
Published: March 2021

The current study was done to measure the role of piperlongumine (PL) on hyperglycemia interrelated oxidative stress‐mediated inflammation and apoptosis, inflammatory stress, and the diabetic insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and glucose transporter 2 (GLUT‐2)/4 signaling pathway in streptozotocin (STZ)‐persuaded diabetic animals. Diabetes was initiated in experimental animals via a single dose intraperitoneal inoculation of STZ. Diabetic rats revealed an augmented blood‐glucose level with drastically diminished plasma‐insulin status. The functions of antioxidants were diminished with enhanced lipid peroxidation, conjugated dienes, and protein carbonyls noticed in diabetic rats'  plasma and pancreatic tissues. An elevation of nuclear factor‐κB (NF‐κB), tumor necrosis factor‐α, and interleukin‐6 proteins was noticed in pancreatic tissues as well as IRS2, AKT, GLUT‐2, and GLUT‐4 marker expressions were quantified in the hepatic tissue of control and diabetic rats. Oral administration of PL for 30 days drastically lowered glucose and higher insulin status in STZ‐induced diabetic rats. Impressively, PL oral supplementation considerably restored the antioxidant levels and reduced inflammation and diabetic marker expressions in STZ‐diabetic rats. These results were supported through a histological study. Moreover, PL also augmented the level of B‐cell lymphoma 2 and diminished the level of Bcl‐2‐associated X protein in STZ‐treated rat's hepatic tissues. Thus, we concluded that PL excellently rescued pancreatic β cells through mitigating hyperglycemia via dynamic insulin secretion, activating antioxidants, and inhibiting inflammation and apoptosis in the pancreatic and hepatic tissue of diabetic rats.
PTHrP promotes development of mouse preimplantation embryos through the AKT/cyclin D1 pathway and nuclear translocation of HDAC4
Authors: Li Yuan‐Yuan , Guo Lei , Li Hui , Lei Wen‐Long , Fan Li‐Hua , Ouyang Ying‐Chun , Hou Yi , Wang Zhen‐Bo , Sun Qing‐Yuan , Lu Sheng‐Sheng , Han Zhiming
Published: March 2021

Parathyroid hormone‐related protein (PTHrP), the main cause of humoral hypercalcemia in malignancies, promotes cell proliferation and delays terminal cell maturation during embryonic development. Our previous study reported that PTHrP plays important roles in blastocyst formation, pluripotency gene expression, and histone acetylation during mouse preimplantation embryonic development. In this study, we further investigated the mechanism of preimplantation embryonic development regulated by PTHrP. Our results showed that Pthrp depletion decreased both the developmental rate of embryos at the cleavage stage and the cell number of morula‐stage embryos. Pthrp‐depleted embryos had significantly decreased levels of cyclin D1, phospho (p)‐AKT (Thr308) and E2F1. However, Pthrp depletion did not cause significant changes in CDK4, β‐catenin or RUNX2 expression. In addition, our results indicated that Pthrp depletion promoted HDAC4 translocation from the cytoplasm to the nucleus in cleavage‐stage embryos by stimulating the activity of protein phosphatase 2A (PP2A), which resulted in dephosphorylation of HDAC4. Taken together, these results suggest that PTHrP regulates cleavage division progression and blastocyst formation through the AKT/cyclin D1 pathway and that PTHrP modulates histone acetylation patterns through nuclear translocation of HDAC4 via PP2A‐dependent HDAC4 dephosphorylation during preimplantation embryonic development in mice.
Atypical Ramsay Hunt syndrome (zoster sine herpete) with otitis media
Authors: Nishizawa Toshinori , Ishikawa Kazuhiro , Matsuo Takahiro , Higuchi Naofumi , Ishiguro Kenji , Mori Nobuyoshi
Published: March 2021

A 21‐year‐old man presented with an acute onset of bilateral throbbing headache, left ear pain, tinnitus, and fever. There was no skin rash on his face. Otoscopy revealed hyperemia and exudate over the left tympanic membrane. The swab culture of the exudate grew methicillin‐sensitive Staphylococcus aureus, and the patient was diagnosed as acute otitis media. Hearing loss and ipsilateral facial paralysis developed on hospital day 4. Despite the absence of typical bullous lesions, serology testing and polymerase chain reaction of the otic exudate for varicella‐zoster virus were positive. The patient was finally diagnosed as zoster sine herpete.
What can cerebrospinal fluid testing and brain autopsies tell us about viral neuroinvasion of SARS‐CoV‐2
Authors: Li Yan‐Chao , Zhang Yan , Tan Bai‐Hong
Published: March 2021

To provide instructive clues for clinical practice and further research of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, we analyzed the existing literature on viral neuroinvasion of SARS‐CoV‐2 in coronavirus disease 2019 (COVID‐19) patients. To date, SARS‐CoV‐2 has been detected in the cerebrospinal fluid (CSF) or brain parenchyma in quite a few patients, which provide undeniable evidence for the neuroinvasive potential of this novel coronavirus. In contrast with the cerebrum and cerebellum, the detection rate of SARS‐CoV‐2 was higher in the olfactory system and the brainstem, both of which also showed severe microgliosis and lymphocytic infiltrations. As compared with the number of patients who underwent viral testing in the central nervous system (CNS), the number of patients showing positive results seems very small. However, it seems too early to conclude that the neuroinvasion of SARS‐CoV‐2 is rare in COVID‐19 patients because the detection methods or sampling procedures in some studies may not be suitable or sufficient to reveal the CNS infection induced by neurotropic viruses. Moreover, the primary symptoms and/or causes of death were distinctly different among examined patients, which probably caused more conspicuous pathological changes than those due to the direct infection that usually localized to specific brain areas. Unfortunately, most autopsy studies did not provide sufficient details about neurological symptoms or suspected diagnoses of the examined patients, and the documentation of neuropathological changes was often incomplete. Given the complex pathophysiology of COVID‐19 and the characteristics of neurotropic viruses, it is understandable that any study of the CNS infection may inevitably have limitations.
Abrupt change in Vietnam coastal upwelling as a response to global warming
Authors: Xu Liqiang , Ji Chao , Kong Deming , Guo Min
Published: March 2021

Coastal upwelling is of great social and economic significance to the human community. The Vietnam coastal upwelling is a fundamental part of upwelling systems in the South China Sea, western Pacific Ocean. However, its sedimentary response to global warming has been largely unknown. Here we reconstruct a 3200‐year sedimentary record based on high‐resolution geochemical analyses of a marine core from off the Vietnamese coast. The results reveal an abrupt sedimentary change since approximately 1950 ce. The abrupt change is explained by concurrent rapid intensification of the coastal upwelling. This can be ascribed to significant global change since the beginning of the 20th century. Global warming could enhance wind speed during the summer and strengthen the coastal upwelling. The forced upwelling results in an increase in nutrient availability and marine primary production; however, ongoing global warming may also increase the risk of more frequent algal blooms in this area.