bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggregation Control, Surface Passivation, and Optimization of Device Structure toward Near‐Infrared Perovskite Quantum‐Dot Light‐Emitting Diodes with an EQE up to 15.4%
Authors: Tseng Zong‐Liang , Chen Lung‐Chien , Chao Li‐Wei , Tsai Meng‐Ju , Luo Dian , Al Amin Nurul Ridho , Liu Shun‐Wei , Wong Ken‐Tsung
Published: March 2022

In recent years, the performance of perovskite quantum dots (QDs) and QD‐based light‐emitting diodes (QLEDs) has improved greatly, with electroluminescence (EL) efficiency of green and red emission exceeding 20%. However, the development of perovskite near‐infrared (NIR) QLEDs has reached stagnation, where the reported maximum EL efficiency is still below 6%, limiting their further applications. In this work, new NIR‐emissive FAPbI3 QDs are developed by post‐treating long alkyl‐encapsulated QDs with 2‐phenylethylammonium iodide (PEAI). The incorporation of PEAI reduces the QD surface defects for giving a high photoluminescence quantum yield up to 61.6%. The n‐octane solution of PEAI‐passivated FAPbI3 QDs is spin coated on top of the PEDOT:PSS‐treated ITO electrode modified with a thermally crosslinked hole‐transporting layer to give a full‐coverage, smooth, and dense QD film. Incorporating with an effective electron‐transporting material, CN‐T2T, which has deep lowest unoccupied molecular orbital and good electron mobility, the optimal device with EL λmax at 772 nm achieves an external quantum efficiency up to 15.4% at a current density of 0.54 mA cm−2 (2.6 V), which is the highest efficiency ever reported for perovskite‐based NIR QLEDs. This study provides a facile strategy to prepare high‐quality perovskite QD films suitable for highly efficient NIR QLED applications.
Sperm Syringe: 3D Sorting Platform for Assisted Reproduction
Authors: Yazdan Parast Farin , O'Bryan Moira K. , Nosrati Reza
Published: March 2022

Selection of high‐quality sperm is crucial to assisted reproduction. However, conventional clinical methods for sperm selection are manual and prone to operator errors. This article presents ‘sperm syringe', a scalable technology that mimics the highly parallelized 3D selection process in vivo via a 3D network of 560 microchannels to select high‐quality sperm. Sperm syringe retrieves more than 41% of healthy sperm from the initial sperm sample in under 15 min, providing a sufficient volume (≈500 µL) and number (1,600,000) of high‐quality sperm for fertility treatments. Experiments with bull and human sperm indicate 65% improvement in selected sperm morphology and DNA integrity, considerably outperforming the current best clinical practices. This approach enables the selection of a subpopulation of high‐quality human sperm from an oligozoospermia sample with DNA integrity below the reference value for fertility. The fabrication method of the device is also simple and scalable, representing a commercially viable technology for translation and clinical adoption. Sperm syringe provides a promising opportunity for clinics to use less invasive assisted reproductive technologies (ARTs) over intracytoplasmic sperm injection, thus reducing the associated clinical workload and optimizing long‐term health outcomes for ART‐conceived children.
Medical Gas Therapy for Tissue, Organ, and CNS Protection: A Systematic Review of Effects, Mechanisms, and Challenges
Authors: Zafonte Ross D. , Wang Lei , Arbelaez Christian A. , Dennison Rachel , Teng Yang D.
Published: March 2022

Gaseous molecules have been increasingly explored for therapeutic development. Here, following an analytical background introduction, a systematic review of medical gas research is presented, focusing on tissue protections, mechanisms, data tangibility, and translational challenges. The pharmacological efficacies of carbon monoxide (CO) and xenon (Xe) are further examined with emphasis on intracellular messengers associated with cytoprotection and functional improvement for the CNS, heart, retina, liver, kidneys, lungs, etc. Overall, the outcome supports the hypothesis that readily deliverable “biological gas” (CO, H2, H2S, NO, O2, O3, and N2O) or “noble gas” (He, Ar, and Xe) treatment may preserve cells against common pathologies by regulating oxidative, inflammatory, apoptotic, survival, and/or repair processes. Specifically, CO, in safe dosages, elicits neurorestoration via igniting sGC/cGMP/MAPK signaling and crosstalk between HO‐CO, HIF‐1α/VEGF, and NOS pathways. Xe rescues neurons through NMDA antagonism and PI3K/Akt/HIF‐1α/ERK activation. Primary findings also reveal that the need to utilize cutting‐edge molecular and genetic tactics to validate mechanistic targets and optimize outcome consistency remains urgent; the number of neurotherapeutic investigations is limited, without published results from large in vivo models. Lastly, the broad‐spectrum, concurrent multimodal homeostatic actions of medical gases may represent a novel pharmaceutical approach to treating critical organ failure and neurotrauma.
Selective Borohydride Oxidation Reaction on Nickel Catalyst with Anion and Cation Exchange Ionomer for High‐Performance Direct Borohydride Fuel Cells
Authors: Ko Youngdon , Lombardo Loris , Li Mo , Pham Thi Ha My , Yang Heena , Züttel Andreas
Published: March 2022

Direct borohydride fuel cells (DBFCs) operate with liquid H2O2 and a high‐energy‐density NaBH4 solution. A facile, direct synthesis method using a non‐noble nickel catalyst for the DBFC anode is shown. The complex anode reaction with an anion‐exchange ionomer (AEI) and a cation‐exchange ionomer (CEI) is evaluated in half‐cell and single‐cell configurations. The ionomer type produces high (AEI) or low local pH (CEI) at the active site of the catalyst in the single‐cell configuration, generating different catalytic reactions. The performance of the nickel catalyst is compared to that of a palladium catalyst. The selective catalytic activities for the borohydride oxidation reaction and hydrogen oxidation reaction are the key parameters for achieving good performance. Furthermore, fuel utilization and H2 evolution measurement in a single‐cell configuration provide more information on the complex anode reaction in the DBFC. The nickel catalyst with CEI on nickel foam (NiF@CEI‐Ni) shows the highest DBFC peak power density (0.59 W cm−2) with a non‐noble metal anode catalyst.
Sexual reproduction is light‐limited as marsh grasses colonize maritime forest
Authors: Kottler Ezra J. , Gedan Keryn B.
Published: March 2022

Climate change is driving abiotic shifts that can threaten the conservation of foundation species and the habitats they support. Directional range shifting is one mechanism of escape, but requires the successful colonization of habitats where interspecific interactions may differ from those to which a species has adapted. For plants with multiple reproductive strategies, these range‐edge interactions may alter the investment or allocation toward a given reproductive strategy. In this study, we quantified sexual reproduction of the clonal marsh grass Spartina patens across an inland colonization front into maritime forest being driven by sea‐level rise. We find that flowering is variable across S. patens meadows, but consistently reduced in low light conditions like those of the forest understory. Observational surveys of S. patens flowering at four sites in the Delmarva Peninsula agreed with the results of two experimental manipulations of light availability (shading experiment in S. patens‐dominated marsh and a forest dieback manipulation). These three approaches pinpointed light limitation as a principal control on S. patens flowering capacity, suggesting that light competition with taller upland species can suppress S. patens flowering along its upland migration front. Consequently, all propagation in shaded conditions must occur clonally or via seeds from the marsh, a reproductive restriction that could limit the potential for local adaptation and reduce genetic diversity. Future research is needed to determine whether the lack of flowering is the result of a trade‐off between sexual and clonal reproduction or results from insufficient photosynthetic products needed to achieve either reproductive method.
Bestimmung von Performance‐Deskriptoren für die CO2‐Hydrierung an alkalimetallpromotierten Katalysatoren auf Eisenbasis
Authors: Yang Qingxin , Kondratenko Vita A. , Petrov Sergey A. , Doronkin Dmitry E. , Saraçi Erisa , Lund Henrik , Arinchtein Aleks , Kraehnert Ralph , Skrypnik Andrey S. , Matvienko Alexander A. , Kondratenko Evgenii V.
Published: March 2022

Alkalimetallpromotoren werden in großem Umfang für die Herstellung heterogener Katalysatoren eingesetzt, die in vielen industriell wichtigen Reaktionen verwendet werden. Die Ursachen für ihre Wirkung sind jedoch in der Regel nur schwer zu ergründen. In dieser Arbeit werden die mechanistischen und kinetischen Aspekte der Wirkung von Alkalimetallen bei der CO2‐Hydrierung an Fe‐haltigen Katalysatoren mithilfe modernster Charakterisierungstechniken sowie räumlich aufgelöster stationärer und instationärer kinetischer Analysen aufgeklärt. Die Promotoren beeinflussen die elektronischen Eigenschaften von Eisen in Eisenkarbiden. Diese Karbideigenschaften bestimmen die Fähigkeit des Katalysators, H2, CO und CO2 zu aktivieren. Die Elektronegativität des Alkalimetallpromoters nach der Allen‐Skala wurde erfolgreich mit der Reaktionsgeschwindigkeit der CO2‐Hydrierung zu höheren Kohlenwasserstoffen und CH4 sowie mit den Geschwindigkeitskonstanten der einzelnen Schritte der CO‐ oder CO2‐Aktivierung korreliert. Die gewonnenen Erkenntnisse können für die Entwicklung und Herstellung von Katalysatoren für andere Reaktionen, bei welchen derartige Promotoren ebenfalls verwendet werden, von Nutzen sein.
Metal–organic frameworks encapsulated with an anticancer compound as drug delivery system: Synthesis, characterization, antioxidant, anticancer, antibacterial, and molecular docking investigation
Authors: El‐Bindary Mohamed A. , El‐Desouky Mohamed G. , El‐Bindary Ashraf A.
Published: March 2022

Metal organic framework (MOF) hybrid materials could be one of the answers in this investigation. We describe a simple and effective encapsulation of doxorubicin (DOX), an anticancer drug, inside Zr‐MOF, which have been little studied as drug delivery organizations. We investigated the measured release of the drug from Zr‐MOF in response to external incentives such as pH changes and interaction with biomimetic schemes. Zr‐MOF with encapsulated doxorubicin (DOX@Zr‐MOF) can be manufactured in one pot by addition the anticancer medication DOX to the reaction combination. They demonstrated pH‐responsive medication release and cancer cell killing capability. MOFs can be designed as multifunctional distribution vehicles for a diversity of loads, including medicinal and imaging agents, using our simple one‐pot approach. Fourier transform infrared (FTIR), X‐ray diffraction, scanning electron microscopy, and N2 sorption isotherm were used to analyze MOF and the developed drug delivery (DOX@Zr‐MOF) scheme. It investigated the effects of MOF and a bespoke drug delivery system on the feasibility of patient breast as well as liver tumor cell lines. At pH 5, the trapped drug can be released more quickly than at pH 7.4. Zr‐MOF nanoparticles had modest cytotoxicity; however, DOX@Zr‐MOF has higher cytotoxicity in MCF‐7 and HepG‐2 cells than DOX at concentrations greater than 31.25 μg ml−1. These results were discovered that DOX@Zr‐MOF could be a promising technique for delivering medicines to cancer cells. Furthermore, using the agar well dispersion technique, Zr‐MOF, DOX, and captured DOX@Zr‐MOF samples were assessed for their potential antibacterial activity against pathogenic bacteria in comparison to traditional antibiotics. In compared to the reference medication Gentamycin, the DOX@Zr‐MOF exhibits a large inhibitory zone against Gram negative organisms (Escherichia coli). The docking active place interactions were assessed to see if DOX might bind to the breast cancer 3hb5‐oxidoreductase receptor, prostate cancer protein 2q7k, and SARS‐CoV‐2 protease 6YB7 for anticancer and anticovid‐19 activities.
The evolving ethics of anatomy: Dissecting an unethical past in order to prepare for a future of ethical anatomical practice
Authors: Comer Amber R.
Published: March 2022

Anatomical practice has arguably one of the most ethically challenging histories in the medical sciences. Among the oldest scientific disciplines in medicine, dissection of the human body for scientific purposes occurred as early as the third century Before the Common Era. Throughout the history of anatomical practice, human dissection has occurred in ways that cross the line from progressing medical science to violating the sanctity of the human body. The dissection of the human body creates ethical dilemmas which stem from the need for anatomical science to gain medical knowledge in juxtaposition with prevailing religious and moral views surrounding anatomy as a threat to the sanctity of the human body. This article examines the unethical history of human dissection throughout the ages and explores the rationale behind the unethical practices. In addition, this article explores imperative modern day ethical standards in anatomy including, the ethical handling of human bodies, respecting human life, and ensuring informed consent for dissection of bodies that are donated. Finally, this article explores the question of which ethical prism we should use when dealing with anatomy collections or works of the past. Learning both the history of unethical practices in anatomy and the rationale behind them is imperative so that the discipline can prepare for an ethical, diverse, and inclusive future. This article provides a foundation for understanding the evolution of ethics in anatomical practice and is a valuable resource for students and anatomists alike.
Collaborate to Protect Vital Source Waters and Mitigate Climate Change
Authors: White Dave , Carpenter Adam T.
Published: March 2022

Key Takeaways

Climate‐friendly agricultural conservation practices can protect and restore drinking water sources.

As US water utilities consider how to better protect their source waters, working with the US Department of Agriculture (USDA) and agricultural producers offers great promise.

Collaboration between water utilities and USDA can also strike a blow against climate change effects—and maybe even save some money in the process.
Laboratory Accreditation Improves Water Quality Data
Authors: Adams Hunter , Reeder Sam , Barker Randall , Thomas Dave , Southard Mark
Published: March 2022

Key Takeaways

Accreditation serves as a demonstration of competency and thus improves overall laboratory quality. To ensure traceable, reliable, defensible data, quality must be approached as a philosophy rather than a program.

The Cypress Environmental Laboratory (CEL), built in 2008, has based its operations on a commitment to high data quality, responsibility, and transparency.

The CEL adheres to a strict standard set by the National Environmental Laboratory Accreditation Program, following practices outlined in the standard for monitoring and maintaining data quality.
Building a House for Stabilizing Lithium‐Metal Anodes
Authors: You Lei , Liu Jianwen , Zhang Hongyu , Zhang Tianren , Wang Juan , Guo Zaiping , Xia Guanglin , Yu Xuebin
Published: March 2022

Lithium (Li) metal is regarded as one of the most promising anode candidates for future high energy density lithium batteries. The practical application of Li‐metal anodes, however, is hindered by the uncontrollable growth of dendrites resulting from both huge volume change and unstable solid‐electrolyte interfaces upon cycling. Herein, we propose a novel “house strategy” that utilizes the 3D NiO nanosheets decorated nickel foam as the frame to confine Li metal and the inorganic [LiNBH]n chains with high Li ion conductivity as the artificial protective proof to establish a stable dendrite‐free Li metal anode. Benefiting from the synergistic effect of the 3D NiO/Ni foam in lowering the local current density and accommodating the huge volume change of Li metal and the [LiNBH]n protective layer in facilitating uniform Li+ diffusion and regulating Li deposition beneath this layer, the LiNBH‐Li@Ni electrode presents an excellent long‐term cycling lifespan of over 800 h at both 1 and 3 mA cm−2 with a high areal capacity of 5 mAh cm−2 in symmetric cells. Upon coupling this anode with LiFePO4 cathode, the thus‐assembled full cells deliver an ultrahigh reversible capacity of 127.4 mAh g−1 at 1 C after 200 cycles.
Electrical stimulation waveform‐dependent osteogenesis on PVDF/BaTiO3 composite using a customized and programmable cell stimulator
Authors: Panda Asish Kumar , Sitaramgupta V S N , Pandya Hardik J. , Basu Bikramjit
Published: March 2022

Directing cellular functionalities using biomaterial‐based bioelectronic stimulation remains a significant constraint in translating research outcomes to address specific clinical needs. Electrical stimulation is now being clinically used as a therapeutic treatment option to promote bone tissue regeneration and to improve neuromuscular functionalities. However, the nature of the electrical waveforms during the stimulation and underlying biophysical rationale are still not scientifically well explored. Furthermore, bone‐mimicking implant‐based bioelectrical regulation of osteoinductivity has not been translated to clinics. The present study demonstrates the role of the electrical stimulation waveform to direct differentiation of stem cells on an electroactive polymeric substrate, using monophasic direct current (DC), square waveform, and biphasic waveform. In this regard, an in‐house electrical stimulation device has been fabricated for the uninterrupted delivery of programmed electrical signals to stem cells in culture. To provide a functional platform for stem cells to differentiate, barium titanate (BaTiO3, BT) reinforced poly(vinylidene difluoride) (PVDF) has been developed with mechanical properties similar to bone. The electrical stimulation of human mesenchymal stem cells (hMSCs) on PVDF/BT composite inhibited proliferation rate at day 7, indicating early commitment for differentiation. The phenotypical characteristics of DC stimulated hMSCs provided signatures of differentiation towards osteogenic lineage, which was subsequently confirmed using alkaline phosphatase assay, collagen deposition, matrix mineralization, and genetic expression. Our findings suggest that DC stimulation induced early osteogenesis in hMSCs with a higher level of intracellular reactive oxygen species (ROS), whereas the stimulation with square wave directed late osteogenesis with a lower ROS regeneration. In summary, the present study critically analyzes the role of electrical stimulation waveforms in regulating osteogenesis, without external biochemical differentiation inducers, on a bone‐mimicking functional biomaterial substrate. Such a strategy can potentially be adopted to develop orthopedic implant‐based bioelectronic medicine for bone regeneration.
A novel synthetic method of peptide nucleic acid (PNA) oligomers using Boc/Cbz‐protected PNA trimer blocks in the solution phase
Authors: Periyalagan Alagarsamy , Hong In Seok
Published: March 2022

In order to use peptide nucleic acid (PNA) oligomers for therapeutic purposes, a high purity level is essential and, in particular, large‐scale production should be easy. However, in the traditional solid‐phase synthesis method, the generation of n − 1 or n − 2 deleted oligomers cannot be completely excluded, and purification of crude oligomers is difficult because the target and impurities overlap. Also, for these reasons, scale‐up is also limited. Here, we report the efficient synthesis of PNA oligomers in the solid phase using fully protected PNA trimers instead of monomers. Fully protected PNA trimer blocks were successfully synthesized via two different routes in the solution phase. When PNA oligomers were synthesized in the solid phase using trimer blocks as monomers, a higher purity level of PNA could be synthesized compared to when oligomers were synthesized using monomers. When using this method, n − 1 or n − 2 truncated products cannot be systematically produced. Furthermore, the trimer blocks coupling method is successful even for sequences containing purine‐rich and/or gamma PNAs, which are difficult to synthesize via the conventional solid‐phase peptide synthesis approach. Finally, two hexameric and one dodecameric PNA oligomers were completely synthesized in the solution phase, with the former showing more than 90% crude purity and the latter showing 70%. We propose that this method may be able to solve several problems related to solid‐phase synthesis at once.
Did court dismiss coach's Title IX claim?
Authors: Lyerly Eric
Published: March 2022

T  he State University of New York at Albany canceled the women's tennis program in the spring of 2016. Former members of the team filed a lawsuit against the university alleging it violated their rights under Title IX.
New 18β‐Glycyrrhetinic Acid‐Emodin Esters Synthetized by a One‐Step Innovative Route, Its Structural Characterization, and in Vivo Toxicity Assessed on Zebrafish Models
Authors: Zhong Yuan , Ding Yuling , Xiao Dandan , Hu Donghua , Li Yong
Published: March 2022

To integrate the active advantages of 18β‐glycyrrhetinic acid (18β‐GA) and emodin, improve bioavailability, increase efficiency, and reduce toxicity, a one‐step innovative synthetic route was set up for the first time: 4‐dimethylaminopyridine (DMAP) was used as catalyst, 1‐ethyl‐(3‐dimethylaminopropyl)carboimide hydrochloride (EDCI) as condensation agent, dry dichloromethane (DCM) as solvent at 25 °C for 12 h, the three target products were obtained and purified by high performance liquid chromatography (HPLC), the chemical structures of them were characterized by nuclear magnetic resonance (NMR) technique and high resolution electron ionization mass spectrometry (HREI‐MS), namely, 18β‐glycyrrhetinic acid‐3‐emodin ester (1, yield 78.83 %, known), di‐18β‐glycyrrhetinic acid‐1‐emodin ester (2, yield 6.49 %, new), and di‐18β‐glycyrrhetinic acid‐8‐emodin ester (3, yield 1.81 %, new). To estimate their effects of the products on toxicity in zebrafish embryos and juvenile fishes, the two precursors and three target products were assayed involving in hatching rate, survival rate, morphology, heart rate, and apoptosis of cardiomyocytes. The results showed that the target products enhanced the hatching and survival rate of zebrafish embryos, decreased the malformation rate and the apoptosis of cardiomyocytes. It should be suggested that the one‐step synthesis route with high yield makes the industrial application of the target products possible due to significantly reduced toxicity. The two new by‐products provide potential candidates for the applications of pharmaceutical industry in the future.
Capture Phosphates via Peptide Self‐assembly to Construct Templates Assisting Mineralization
Authors: Shao Liang , Liu Shichang , Li Guanying , Zhang Ye
Published: March 2022

The development of synthetic scaffolds for template‐guided mineralization of calcium phosphates (CaP) is an ongoing challenge in biomimetic material design for bone graft substitute. To mimic the extracellular matrix (ECM)‐organized biomineralization, polymer‐induced liquid precursor (PILP) phase has been widely applied in the construction of biomineralized tissues. We proposed here a peptide self‐assembled scaffold as an easier fabricated alternative of charged polymers for PILP template. An arginine enriched pentapeptide was synthesized to serve as the basic building block for the construction of positively charged nanofibrils at physiological condition. By binding with multiple arginine residues via electrostatic interactions, phosphates cross‐link nanofibrils forming phosphate enriched scaffold to assist the mineralization of CaP during the calcium ion infiltration. The obtained CaP mineralized scaffold exhibited competent properties to polymer‐based biominerals with enhanced mechanical properties and reversible deformations, as well as good biocompatibility, promising great potentials as mimetic bone matrix.
Amide Bonds Meet Flow Chemistry: A Journey into Methodologies and Sustainable Evolution
Authors: Alfano Antonella Ilenia , Lange Heiko , Brindisi Margherita
Published: March 2022

Invited for this month′s cover are Antonella Ilenia Alfano and Margherita Brindisi (University of Naples Federico II) and Heiko Lange (University of Milano Bicocca). The cover image highlights the impact of greener and more sustainable flow chemistry protocols applied to amide bond formation. The Review itself is available at 10.1002/cssc.202102708.
Outcome and prognostic value of N‐terminal pro‐brain natriuretic peptide and high‐sensitivity C‐reactive protein in mildly dilated cardiomyopathy vs. dilated cardiomyopathy
Authors: Feng Jiayu , Tian Pengchao , Liang Lin , Chen Yuyi , Wang Yunhong , Zhai Mei , Huang Yan , Zhou Qiong , Zhao Xuemei , Zhao Lang , Huang Boping , Huang Liyan , Zhang Yuhui , Zhang Jian
Published: March 2022

Aims

Mildly dilated cardiomyopathy (MDCM) was characterized as a subset of dilated cardiomyopathy (DCM) with systolic dysfunction and modest ventricular dilatation, of which the prognostic studies were limited. We aimed to compare the prognostic value of the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and high‐sensitivity C‐reactive protein (hs‐CRP) between MDCM and DCM.

Methods and results

We retrospectively included hospitalized patients diagnosed with DCM and a left ventricular ejection fraction ≤ 50% at Fuwai Hospital from 2006 to 2017. MDCM was defined as left ventricular end‐diastolic diameter index (LVEDDi) ≤ 33 mm/m2 in males and ≤34 mm/m2 in females. A total of 640 patients (median age 49 years, 24.8% female) were included in this study. At baseline, 110 cases (17%) were categorized as MDCM and 529 cases (83%) as DCM. Of 282 patients who had follow‐up echocardiograms ≥ 6 months, 7 MDCM patients (11.1%) evolved to DCM and 70 DCM patients (32.0%) recovered to MDCM by the change of LVEDDi. Compared with DCM, patients with baseline MDCM had lower composite risks of all‐cause mortality, heart transplantation, and heart failure rehospitalization [adjusted hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.43–0.93, P = 0.019]. Both hs‐CRP and NT‐proBNP were independently associated with the composite endpoint in the overall cohort (hs‐CRP: adjusted HR 1.07, 95% CI 1.00–1.15, P = 0.036; NT‐proBNP: adjusted HR 1.11, 95% CI 1.02–1.22, P = 0.019). After a propensity‐score matching between MDCM and DCM, higher NT‐proBNP (above the median) was significantly associated with the outcome in DCM patients (HR 1.83, 95% CI 1.05–3.20, P = 0.034), but not in MDCM patients (HR 1.54, 95% CI 0.76–3.11, P = 0.227). On the contrary, higher hs‐CRP (above the median) showed prognostic value for adverse events in MDCM patients (HR 3.19, 95% CI 1.52–6.66, P = 0.002), but not in DCM patients (HR 1.04, 95% CI 0.61–1.79, P = 0.88).

Conclusions

In patients with MDCM, although no evidence suggested the prognostic role of NT‐proBNP, higher level of hs‐CRP was associated with outcome, supporting the use of hs‐CRP in risk stratification for patients with MDCM.
GEQO: The Hub of Organometallic Chemistry in the Spanish Royal Society of Chemistry
Authors: Albéniz Ana C.
Published: March 2022

The Specialized Group of Organometallic Chemistry (Grupo Especializado de Química Organometálica, GEQO) was created within the Spanish Royal Society of Chemistry (RSEQ) in 1981, and organometallic chemistry research has grown immensely in Spain since then. Guest Editor Ana Albéniz, EurJIC’s Editorial Board Chair and president of the GEQO, briefly introduces the Specialized Group of Organometallic Chemistry (Grupo Especializado de Química Organometálica, GEQO) of the Spanish Royal Society of Chemistry (RSEQ) and presents EurJIC’s RSEQ‐GEQO Prizewinners Special Collection.
SnCl2‐Catalyzed Acetalation/Selective Benzoylation Sequence for the Synthesis of Orthogonally Protected Glycosyl Acceptors
Authors: Lv Jian , Liu Chun‐Yang , Guo Yang‐Fan , Feng Guang‐Jing , Dong Hai
Published: March 2022

Based on SnCl2‐catalyzed acetalation and selective benzoylation, a one‐pot strategy to efficiently synthesize orthogonally protected glycosyl acceptors with 2‐OH/3‐OH was developed. Consequently, 2‐OBz or 3‐OBz 4,6‐O‐benzylidene galactosides and glucosides were efficiently prepared in moderate to high yields starting from free galactosides and glucosides, and were used as valuable glycosyl acceptors for the synthesis of blood group antigens O and B analogues in this study.
Global intercompany assessment of ICIEF platform comparability for the characterization of therapeutic proteins
Authors: Madren Seth , McElroy Will , Schultz‐Kuszak Kristin , Boumajny Boris , Shu Yao , Sautter Sabine , Zhao Helen C. , Schadock‐Hewitt Abby , Chumsae Chris , Ball Nancy , Zhang Xiaoying , Rish Kimberly , Zhang Shukui , Wurm Christine , Cai Sumin , Bauer Scott P. , Stella Cinzia , Zheng Laura , Roper Brian , Michels David A. , Wu Gang , Kocjan Bostjan , Birk Matej , Erdmann Simon Erik , He Xiaoping , Whittaker Brad , Song Yvonne , Barrett Hannah , Strozyk Kevin , Jing Ye , Huang Long , Mhatre Vishal , McLean Paul , Yu Tiantian , Yang Huijuan , Mattila Minna
Published: March 2022

An international team spanning 19 sites across 18 biopharmaceutical and in vitro diagnostics companies in the United States, Europe, and China, along with one regulatory agency, was formed to compare the precision and robustness of imaged CIEF (ICIEF) for the charge heterogeneity analysis of the National Institute of Standards and Technology (NIST) mAb and a rhPD‐L1‐Fc fusion protein on the iCE3 and the Maurice instruments. This information has been requested to help companies better understand how these instruments compare and how to transition ICIEF methods from iCE3 to the Maurice instrument. The different laboratories performed ICIEF on the NIST mAb and rhPD‐L1‐Fc with both the iCE3 and Maurice using analytical methods specifically developed for each of the molecules. After processing the electropherograms, statistical evaluation of the data was performed to determine consistencies within and between laboratory and outlying information. The apparent isoelectric point (pI) data generated, based on two‐point calibration, for the main isoform of the NIST mAb showed high precision between laboratories, with RSD values of less than 0.3% on both instruments. The SDs for the NIST mAb and the rhPD‐L1‐Fc charged variants percent peak area values for both instruments are less than 1.02% across different laboratories. These results validate the appropriate use of both the iCE3 and Maurice for ICIEF in the biopharmaceutical industry in support of process development and regulatory submissions of biotherapeutic molecules. Further, the data comparability between the iCE3 and Maurice illustrates that the Maurice platform is a next‐generation replacement for the iCE3 that provides comparable data.
Impact of soil‐structure interaction on the effectiveness of Tuned Mass Dampers
Authors: Gorini Davide Noè , Chisari Corrado
Published: March 2022

Tuned Mass Dampers (TMDs) can represent an attracting solution to mitigate vibrations of a structure under seismic excitation, but their effectiveness can be considerably altered by the dynamic interaction with the foundation soil. The available design criteria for TMDs do not account for these effects and can therefore lead to a non‐optimised structural performance. In this paper an investigation on the dynamic interaction of the TMD with the whole soil‐structure system is presented, with the objective of highlighting the system parameters governing the response and the effectiveness of the device as seismic protection. An interpretative model of the soil‐structure‐TMD system expressed in a rigorous non‐dimensional form is proposed, and an extensive global sensitivity analysis on its performance under harmonic loading is carried out. The identification of the typical performance regions shows that the seismic effectiveness of a TMD is mainly controlled by a limited number of parameters describing the structural behaviour and the soil‐structure interaction, such as the structure‐to‐soil relative stiffness and those governing foundation rocking. The non‐dimensional system parameters leading to either a favourable or detrimental effect on the TMD performance due to soil‐structure interaction are also identified, and two design methodologies proposed in the literature are critically assessed in light of the framework proposed.
Investigation of sintering properties and ceramifying process of amorphous silica/mica‐based ceramifiable polyethylene composites
Authors: Shen Jiapei , Sun Qing , Li Lang , Zhang Jian , Sheng Jiawei
Published: March 2022

Ceramifiable polyolefin‐based composites are promising materials for fire‐resistant cables. Many studies have been focused on improving the ceramifiable properties by developing various composite matrixes with optimum inorganic fillers. Few studies have been carried out to compare the sintering properties of ceramifying powder (CP) and ceramifiable polymer‐based composites directly. In this work, a low‐temperature sintering CP, formulated with mica, amorphous silica and glass frits, and filled into polyethylene (PE) matrix to prepare a ceramifiable PE composites (CPE). The sintering properties, including the flexural strength, apparent porosity and volume variation, were tested at calcination temperatures from 600 to 900°C. Results showed that the CP had better sintering properties than the CPE at the same calcined temperatures, but the gap between the two continued to decrease as the temperature increased. The negative effect of PE matrix decomposition on the ceramifying process was more pronounced in the low‐temperature ranges (600 and 700°C). As the temperature reached above 700°C, the sintering of the CP was accelerated, and the sintering properties of composite residue increased significantly. The ceramifying process of the CPE was investigated by thermalgravimetric analysis, X‐ray diffraction and scanning electron microscopy. The analyses demonstrated that the induction of the CP improved the thermal stability of the CPE, and played the main role in the structure evolution of the composite residue. During the ceramifying process, the glass frits melted at low temperatures, bridging mica and amorphous silica. As the temperature increased to 800 and 900°C, mica had a eutectic reaction with the glass liquid phase, facilitating the change of a bridging structure to the continuous island structure responsible for the superior mechanical and fire‐resistant properties of the CPE.
Single‐Cell Transcriptome Identifies Drug‐Resistance Signature and Immunosuppressive Microenvironment in Metastatic Small Cell Lung Cancer
Authors: Zhang Jing , Zhang Haiping , Zhang Lele , Li Dianke , Qi Mengfan , Zhang Liping , Yu Huansha , Wang Di , Jiang Gening , Wang Xujun , Zhu Xianmin , Zhang Peng
Published: March 2022

Small cell lung cancer (SCLC) is a deadly neuroendocrine malignancy with high metastasis. However, the heterogeneity of metastatic SCLC at the single‐cell level remains elusive. The single‐cell transcriptome of a total of 24 081 cells in metastatic lymph node samples from seven SCLC patients via endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is examined. Genomic alterations are also examined by whole exome sequencing (WES) and the immune infiltration between SCLC and non‐SCLC (NSCLC) is compared using public single‐cell RNA sequencing (scRNA‐seq) data. It is identified that malignant cells in lymph‐node metastatic SCLC have inter‐patient and intra‐tumor heterogeneity characterized by distinct ASCL1 and NEUROD1 expression patterns. High expression of genes such as FZD8 in WNT pathway is associated with drug resistance in malignant cells. Compared to NSCLC, SCLC harbors a unique immunosuppressive tumor microenvironment. Malignant cells exhibit a pattern of attenuated MHC‐I antigen presentation‐related gene expression, which is associated with relatively low proportion of exhausted T cells. Natural killer (NK) cells display impaired antitumor function with high expression of TGFBR2. This work characterizes the inter‐patient and intra‐tumor heterogeneity of metastatic SCLC and uncovers the exhaustion signatures in NK cells, which may pave the way for novel treatments for SCLC including immune checkpoint blockade‐based immunotherapy.
Privacy‐preserving quality control of neuroimaging datasets in federated environments
Authors: Saha Debbrata K. , Calhoun Vince D. , Du Yuhui , Fu Zening , Kwon Soo Min , Sarwate Anand D. , Panta Sandeep R. , Plis Sergey M.
Published: March 2022

Privacy concerns for rare disease data, institutional or IRB policies, access to local computational or storage resources or download capabilities are among the reasons that may preclude analyses that pool data to a single site. A growing number of multisite projects and consortia were formed to function in the federated environment to conduct productive research under constraints of this kind. In this scenario, a quality control tool that visualizes decentralized data in its entirety via global aggregation of local computations is especially important, as it would allow the screening of samples that cannot be jointly evaluated otherwise. To solve this issue, we present two algorithms: decentralized data stochastic neighbor embedding, dSNE, and its differentially private counterpart, DP‐dSNE. We leverage publicly available datasets to simultaneously map data samples located at different sites according to their similarities. Even though the data never leaves the individual sites, dSNE does not provide any formal privacy guarantees. To overcome that, we rely on differential privacy: a formal mathematical guarantee that protects individuals from being identified as contributors to a dataset. We implement DP‐dSNE with AdaCliP, a method recently proposed to add less noise to the gradients per iteration. We introduce metrics for measuring the embedding quality and validate our algorithms on these metrics against their centralized counterpart on two toy datasets. Our validation on six multisite neuroimaging datasets shows promising results for the quality control tasks of visualization and outlier detection, highlighting the potential of our private, decentralized visualization approach.
mRNA and gene editing: Late breaking therapies in liver diseases
Authors: Zabaleta Nerea , Torella Laura , Weber Nicholas D. , Gonzalez‐Aseguinolaza Gloria
Published: March 2022

The efficient delivery of RNA molecules to restore the expression of a missing or inadequately functioning protein in a target cell and the intentional specific modification of the host genome using engineered nucleases represent therapeutic concepts that are revolutionizing modern medicine. The initiation of several clinical trials using these approaches to treat metabolic liver disorders as well as the recently reported remarkable results obtained by patients with transthyretin amyloidosis highlight the advances in this field and show the potential of these therapies to treat these diseases safely and efficaciously. These advances have been possible due, firstly, to significant improvements made in RNA chemistry that increase its stability and prevent activation of the innate immune response and, secondly, to the development of very efficient liver‐targeted RNA delivery systems. In parallel, the breakout of CRISPR/CRISPR‐associated 9–based technology in the gene editing field has marked a turning point in in vivo modification of the cellular genome with therapeutic purposes, which can be based on gene supplementation, correction, or silencing. In the coming years we are likely to witness the therapeutic potential of these two strategies both separately and in combination. In this review we summarize the preclinical data obtained in animal models treated with mRNA as a therapeutic agent and discuss the different gene editing strategies applied to the treatment of liver diseases, highlighting both their therapeutic efficacy as well as safety concerns.
Ten‐eleven translocation‐2 inactivation restrains IL‐10‐producing regulatory B cells to enable antitumor immunity in hepatocellular carcinoma
Authors: Lu Zhou , Liu Ronghua , Wang Yining , Jiao Mengxia , Li Zhongchen , Wang Zhiqiang , Huang Cheng , Shi Guoming , Ke Aiwu , Wang Luman , Fu Ying , Xia Jie , Wen Haoyu , Zhou Jian , Wang Xiaoying , Ye Dan , Fan Jia , Chu Yiwei , Cai Jiabin
Published: March 2022

Background and Aims:

IL‐10‐producing regulatory B cells (IL‐10+B cells), a dominant regulatory B cell (Breg) subset, foster tumor progression. However, the mechanisms underlying their generation in HCC are poorly understood. Ten‐eleven translocation‐2 (TET2), a predominant epigenetic regulatory enzyme in B cells, regulates gene expression by catalyzing demethylation of 5‐methylcytosine into 5‐hydroxymethyl cytosine (5hmC). In this study, we investigated the role of TET2 in IL‐10+B cell generation in HCC and its prospects for clinical application.

Approach and Results:

TET2 activation in B cells triggered by oxidative stress from the HCC microenvironment promoted IL‐10 expression, whereas adoptive transfer of Tet2‐deficient B cells suppressed HCC progression. The aryl hydrocarbon receptor is required for TET2 to hydroxylate Il10. In addition, high levels of IL‐10, TET2, and 5hmc in B cells indicate poor prognosis in patients with HCC. Moreover, we determined TET2 activity using 5hmc in B cells to evaluate the efficacy of anti‐programmed death 1 (anti‐PD‐1) therapy. Notably, TET2 inhibition in B cells facilitates antitumor immunity to improve anti‐PD‐1 therapy for HCC.

Conclusions:

Our findings propose a TET2‐dependent epigenetic intervention targeting IL‐10+B cell generation during HCC progression and identify the inhibition of TET2 activity as a promising combination therapy with immune checkpoint inhibitors for HCC.
The effect of probiotics on gestational diabetes and its complications in pregnant mother and newborn: A systematic review and meta‐analysis during 2010–2020
Authors: Mahdizade Ari Marzie , Teymouri Samane , Fazlalian Tayebeh , Asadollahi Parisa , Afifirad Roghayeh , Sabaghan Mohammad , Valizadeh Fateme , Ghanavati Roya , Darbandi Atieh
Published: March 2022

This study was aimed to evaluate the effect of probiotics consumption on gestational diabetes (GD) and its complications in pregnant mother and newborn. The study was registered on PROSPERO (CRD42021243409) and all the enrolled articles were collected from four databases (Medline, Scopus, Embase, and Google Scholar) as randomized controlled trials (RCTs) from 2010 to 2020. A total of 4865 study participants from 28 selected studies were included in this review. The present meta‐analysis showed that the consumption of probiotics supplementation has the potential to decrease GD‐predisposing metabolic parameters such as blood glucose level, lipid profile, inflammation, and oxidative markers which may reduce GD occurrence among pregnant women.
Blood long non‐coding RNA intersectin 1–2 is highly expressed and links with increased Th17 cells, inflammation, multiple organ dysfunction, and mortality risk in sepsis patients
Authors: Huang Qinghe , Wang Yibin , He Fuyun
Published: March 2022

Background

Long non‐coding RNA intersectin 1–2 (lnc‐ITSN1‐2) exacerbates inflammation and promotes T‐helper (Th) cell differentiation, also serves as a biomarker in critical illness diseases. However, its clinical role in sepsis remains obscure. Hence, the study aimed to explore the relationship of lnc‐ITSN1‐2 with Th cells, inflammation, disease severity, multiple organ dysfunction, and mortality risk in sepsis.

Methods

Peripheral blood mononuclear cells (PBMC) were isolated from 95 sepsis patients and 50 health controls, followed by lnc‐ITSN1‐2 evaluation using RT‐qPCR. PBMC Th1, Th17 cells and their secreted cytokines in serum were detected by flow cytometry and ELISA, respectively.

Results

Lnc‐ITSN1‐2 in sepsis patients was higher than it in health controls (Z = −7.328, p < 0.001). Lnc‐ITSN1‐2 correlated with increased interferon‐gamma (p = 0.009), Th17 cells (p = 0.022), and interleukin‐17A (p = 0.006), but not Th1 cells (p = 0.169) in sepsis patients. Moreover, lnc‐ITSN1‐2 had a positive connection with C‐reactive protein (p = 0.001), acute pathologic and chronic health evaluation (APACHE) II (p = 0.024), and sequential organ failure assessment (SOFA) scores (p = 0.022). Regarding SOFA subscales, lnc‐ITSN1‐2 linked with elevated respiratory system score (p = 0.005), cardiovascular system score (p = 0.007), and renal system score (p = 0.004) but no other subscales. Besides, lnc‐ITSN1‐2 had an increasing trend, but no statistical difference, in septic deaths compared to survivors (Z = −1.852, p = 0.064).

Conclusion

Lnc‐ITSN1‐2 reflects sepsis progression and unfavorable prognosis to some extent, which may serve as a potential biomarker to improve the management of sepsis patients.
ACSL4 contributes to ferroptosis‐mediated rhabdomyolysis in exertional heat stroke
Authors: He Sixiao , Li Ru , Peng Yanmei , Wang Ziqing , Huang Junhao , Meng Hongen , Min Junxia , Wang Fudi , Ma Qiang
Published: March 2022

Background

Rhabdomyolysis (RM) is a common complication of exertional heat stroke (EHS) and constitutes a direct cause of death. However, the mechanism underlying RM following EHS remains unclear.

Methods

The murine EHS model was prepared by our previous protocol. RNA sequencing is applied to identify the pathological pathways that contribute to RM following EHS. Inhibition of the acyl‐CoA synthetase long‐chain family member 4 (ACSL4) was achieved by RNA silencing in vitro prior to ionomycin plus heat stress exposure or pharmacological inhibitors in vivo prior to heat and exertion exposure. The histological changes, the iron accumulation, oxidized phosphatidylethanolamines species, as well as histological evaluation and levels of lipid metabolites in skeletal muscle tissues were measured.

Results

We demonstrated that ferroptosis contributes to RM development following EHS. Ferroptosis inhibitor ferrostatin‐1 administration once EHS onset significantly ameliorated the survival rate of EHS mice from 35.357% to 52.288% within 24 h after EHS (P = 0.0028 compared with control) and markedly inhibited RM development induced by EHS. By comparing gene expression of between sham heat rest (SHR) (n = 3) and EHS (n = 3) mice in the gastrocnemius (Gas) muscle tissue, we identified that Acsl4 mRNA expression is elevated in Gas muscle tissue of EHS mice (P = 0.0038 compared with SHR), so as to its protein levels (P = 0.0001 compared with SHR). Followed by increase in creatine kinase (CK) and myoglobin (MB) levels, the labile iron accumulation, decrease in glutathione peroxidase 4 (GPX4) expression, and elevation of lipid peroxidation products. From in vivo and in vitro experiments, inhibition of Acsl4 significantly improves muscle cell death caused by EHS, thereby ameliorating RM development, followed by reduction in CK and MB levels by 30–40% (P < 0.0001; n = 8–10) and 40% (P < 0.0001; n = 8–10), restoration of GPX4 expression, and decrease in lipid peroxidation products. Mechanistically, ACSL4‐mediated RM seems to be Yes‐associated protein (YAP) dependent via TEA domain transcription factor1/TEA domain transcription factor4.

Conclusions

These findings demonstrate an important role of ACSL4 in mediating ferroptosis activation in the development of RM following EHS and suggest that targeting ACSL4 may represent a novel therapeutic strategy to limit the skeletal muscle cell death and prevent RM after EHS.
Highly exo selective, photochemically promoted cyclization of iodoallene derivatives
Authors: Jovanovic Milos , Simic Milena , Petkovic Milos , Tasic Gordana , Maslak Veselin , Jovanovic Predrag , Savic Vladimir
Published: March 2022

A photochemically promoted intramolecular cyclization of aryl‐, vinyl‐, and alkyliodo allenes has been developed. The optimal conditions employed [Ir(ppy)2(dtbbpy)]PF6 (1 mol%) as catalyst affording products with high exo selectivity in moderate to good yields. Chiral substrates showed diastereoselectivity of up to 95/5 favoring trans product.