bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteriophobic Zwitterionic/Dopamine Coatings for Medical Elastomers
Authors: Texidó Robert , Cabanach Pol , Kaplan Richard , García‐Bonillo Cristina , Pérez Darío , Zhang Shuo , Borrós Salvador , Pena‐Francesch Abdon
Published: September 2022

Despite modern advancements in sterilization and medical practices, bacterial infections remain a significant concern in the implantation of medical devices. There is currently an urgent need for long‐lasting and high‐stable strategies to avoid the adhesion of bacteria to the wide range of materials present in medical devices. Here, a versatile methodology to create anti‐biofouling coatings that prevent the adhesion of bacteria to silicone‐based materials used in healthcare is reported. These coatings consist of bifunctional ethylene glycol dimethacrylate as an anchor between a zwitterionic polymer (SBMA), which provides antifouling properties, and a polydopamine layer that operates as an interfacial binder, providing mechanical strength and strong adhesion to elastomeric substrates. The coatings exhibit superhydrophilic and anti‐biofouling properties, creating a strong “bacteriophobic effect” that leads to a >99% reduction in bacterial adhesion. This bacteriophobic coating is successfully implemented and validated in a commercial urinary catheter, reducing bacterial adhesion by 1–2 orders of magnitude and avoiding bacterial colonization to prevent catheter‐associated urinary tract infections. The results presented here demonstrate the versatility, durability, and scalability of the coating methodology for preventing bacterial adhesion in silicone elastomers, which can be easily applied to other elastomeric materials used in medical devices beyond urinary tract infection prevention.
Dual Patterning of Self‐Assembling Spider Silk Protein Nanofibrillar Networks
Authors: Lamberger Zan , Kocourková Karolína , Minařík Antonín , Humenik Martin
Published: September 2022

Self‐assembly of a recombinant spider silk protein into nanofibrillar networks in combination with photolithography is used to produce diversely functionalized micropattern. Amino‐modified substrates coated with a positive tone photoresist are processed into 1 µm deep arbitrarily shaped microwells, at the bottom of which spider silk proteins are covalently coupled to the deprotected aminated surface. The protein layer serves to seed the self‐assembly of nanofibrils from the same protein in the microwells, forming immobilized few nanometers thin networks after the stripping of the photoresist. The nanofibrous micropattern can be functionalized by employing fluorescently modified spider silk variants during the self‐assembly or by later covalent modification with nucleic acids. By repeating the photolithography and fibril assembly procedures, two functionally different and spatially defined pattern are created.
2+δ‐Dimensional Materials via Atomistic Z‐Welding
Authors: Sahu Tumesh Kumar , Motlag Maithilee , Bandyopadhyay Arkamita , Kumar Nishant , Cheng Gary J. , Kumar Prashant
Published: September 2022

Pivotal to functional van der Waals stacked flexible electronic/excitonic/spintronic/thermoelectric chips is the synergy amongst constituent layers. However; the current techniques viz. sequential chemical vapor deposition, micromechanical/wet‐chemical transfer are mostly limited due to diffused interfaces, and metallic remnants/bubbles at the interface. Inter‐layer‐coupled 2+δ‐dimensional materials, as a new class of materials can be significantly suitable for out‐of‐plane carrier transport and hence prompt response in prospective devices. Here, the discovery of the use of exotic electric field ≈106 V cm−1 (at microwave hot‐spot) and 2 thermomechanical conditions i.e. pressure ≈1 MPa, T ≈ 200 °C (during solvothermal reaction) to realize 2+δ‐dimensional materials is reported. It is found that PzPz chemical bonds form between the component layers, e.g., CB and CN in G‐BN, MoN and MoB in MoS2‐BN hybrid systems as revealed by X‐ray photoelectron spectroscopy. New vibrational peaks in Raman spectra (BC ≈1320 cm–1 for the G‐BN system and MoB ≈365 cm–1 for the MoS2‐BN system) are recorded. Tunable mid‐gap formation, along with diodic behavior (knee voltage ≈0.7 V, breakdown voltage ≈1.8 V) in the reduced graphene oxide‐reduced BN oxide (RGO‐RBNO) hybrid system is also observed. Band‐gap tuning in MoS2‐BN system is observed. Simulations reveal stacking‐dependent interfacial charge/potential drops, hinting at the feasibility of next‐generation functional devices/sensors.
Revealing the Electrophilic‐Attack Doping Mechanism for Efficient and Universal p‐Doping of Organic Semiconductors
Authors: Guo Jing , Liu Ying , Chen Ping‐An , Wang Xinhao , Wang Yanpei , Guo Jing , Qiu Xincan , Zeng Zebing , Jiang Lang , Yi Yuanping , Watanabe Shun , Liao Lei , Bai Yugang , Nguyen Thuc‐Quyen , Hu Yuanyuan
Published: September 2022

Doping is of great importance to tailor the electrical properties of semiconductors. However, the present doping methodologies for organic semiconductors (OSCs) are either inefficient or can only apply to some OSCs conditionally, seriously limiting their general applications. Herein, a novel p‐doping mechanism is revealed by investigating the interactions between the dopant trityl tetrakis(pentafluorophenyl) borate (TrTPFB) and poly(3‐hexylthiophene) (P3HT). It is found that electrophilic attack of the trityl cations on thiophenes results in the formation of tritylated thiophenium ions, which subsequently induce electron transfer from neighboring P3HT chains to realize p‐doping. This unique p‐doping mechanism enables TrTPFB to p‐dope various OSCs including those with high ionization energy (IE ≈ 5.8 eV). Moreover, this doping mechanism endows TrTPFB with strong doping capability, leading to doping efficiency of over 80% in P3HT. The discovery and elucidation of this novel doping mechanism not only points out that strong electrophiles are a class of efficient p‐dopants for OSCs, but also provides new opportunities toward highly efficient doping of various OSCs.
Quantitative and Real‐Time Evaluation of Human Respiration Signals with a Shape‐Conformal Wireless Sensing System
Authors: Chen Sicheng , Qian Guocheng , Ghanem Bernard , Wang Yongqing , Shu Zhou , Zhao Xuefeng , Yang Lei , Liao Xinqin , Zheng Yuanjin
Published: September 2022

Respiration signals reflect many underlying health conditions, including cardiopulmonary functions, autonomic disorders and respiratory distress, therefore continuous measurement of respiration is needed in various cases. Unfortunately, there is still a lack of effective portable electronic devices that meet the demands for medical and daily respiration monitoring. This work showcases a soft, wireless, and non‐invasive device for quantitative and real‐time evaluation of human respiration. This device simultaneously captures respiration and temperature signatures using customized capacitive and resistive sensors, encapsulated by a breathable layer, and does not limit the user's daily life. Further a machine learning‐based respiration classification algorithm with a set of carefully studied features as inputs is proposed and it is deployed into mobile clients. The body status of users, such as being quiet, active and coughing, can be accurately recognized by the algorithm and displayed on clients. Moreover, multiple devices can be linked to a server network to monitor a group of users and provide each user with the statistical duration of physiological activities, coughing alerts, and body health advice. With these devices, individual and group respiratory health status can be quantitatively collected, analyzed, and stored for daily physiological signal detections as well as medical assistance.
Toward Excellence in Photocathode Engineering for Photoelectrochemical CO2 Reduction: Design Rationales and Current Progress
Authors: Putri Lutfi Kurnianditia , Ng Boon‐Junn , Ong Wee‐Jun , Chai Siang‐Piao , Mohamed Abdul Rahman
Published: September 2022

Photoelectrochemical CO2 reduction reaction (PEC CO2RR) is a promising technology which offers the possibility of a carbon‐neutral solar fuel production via artificial photosynthesis. The challenging proton‐coupled multielectron transfers with high energy barriers in CO2RR however pose as a huge hindrance to the technology, which demands strict specifications in the design of photocathode materials so as to improve PEC performances. This review underscores effective design strategies and current material progress for the judicious assembly of photocathode materials for CO2RR. The review begins with elucidating the fundamental principles of CO2 reduction process and photocathode electrochemistry. Based on these, the design criteria and trade‐offs in the design of PEC CO2RR photocathodes are highlighted. The various promotive strategies for photocathodes and their underlying rationales such as doping, defect engineering, nanostructuring, cocatalyst loading, passivation, heterojunction formation, and innovative multijunction configurations are further outlined and design propositions in the area are provided. Following that, various photocathode semiconductor materials categorized into photovoltaic (PV) grade (silicon, III–V semiconductors, chalcogenides) and non‐PV grade (metal oxides) materials are summarized and extensively discussed, along with their recent advances. Finally, perspectives on the design of photocathodes for CO2RR and new paradigms in the field are put forward.
Missing data in bioarchaeology II: A test of ordinal and continuous data imputation
Authors: Wissler Amanda , Blevins Kelly E. , Buikstra Jane E.
Published: September 2022

Objectives

Previous research has shown that while missing data are common in bioarchaeological studies, they are seldom handled using statistically rigorous methods. The primary objective of this article is to evaluate the ability of imputation to manage missing data and encourage the use of advanced statistical methods in bioarchaeology and paleopathology. An overview of missing data management in biological anthropology is provided, followed by a test of imputation and deletion methods for handling missing data.

Materials and Methods

Missing data were simulated on complete datasets of ordinal (n = 287) and continuous (n = 369) bioarchaeological data. Missing values were imputed using five imputation methods (mean, predictive mean matching, random forest, expectation maximization, and stochastic regression) and the success of each at obtaining the parameters of the original dataset compared with pairwise and listwise deletion.

Results

In all instances, listwise deletion was least successful at approximating the original parameters. Imputation of continuous data was more effective than ordinal data. Overall, no one method performed best and the amount of missing data proved a stronger predictor of imputation success.

Discussion

These findings support the use of imputation methods over deletion for handling missing bioarchaeological and paleopathology data, especially when the data are continuous. Whereas deletion methods reduce sample size, imputation maintains sample size, improving statistical power and preventing bias from being introduced into the dataset.
Impaired B Cell Expression of the Inhibitory Fcγ Receptor IIB in Myasthenia Gravis
Authors: Keller Christian W. , Chuquisana Omar , Derdelinckx Judith , Gross Catharina C. , Berger Klaus , Robinson James , Nimmerjahn Falk , Wiendl Heinz , Willcox Nick , Lünemann Jan D.
Published: September 2022

Myasthenia gravis (MG) is an autoimmune disease in which pathogenic immunoglobulin G antibodies bind to acetylcholine receptors (or to functionally related molecules at the neuromuscular junction). B cell expression of the inhibitory immunoglobulin G receptor, Fc‐gamma receptor (FcγR) IIB, maintains peripheral immune tolerance, and its absence renders B cells hyperresponsive to autoantigen. Here, we report that FcγRIIB expression levels are substantially reduced in B lineage cells derived from immunotherapy‐naïve patients with acetylcholine receptor antibody‐positive early‐onset MG. In contrast, genetic variants associated with impaired FcγRIIB expression are not enriched in MG, indicating post‐transcriptional dysregulation. FcγR‐targeted therapies could have therapeutic benefits in MG. ANN NEUROL 2022;92:1046–1051
sp2 to sp3 Hybridization Transformation in Ionic Crystals under Unprecedentedly Low Pressure
Authors: Jiang Xingxing , Molokeev Maxim S. , Wang Naizheng , Wang Yonggang , Wen Ting , Dong Zhichao , Liu Youquan , Li Wei , Lin Zheshuai
Published: September 2022

Under cold pressure sp1/sp2‐to‐sp3 hybridization transformation has been exclusively observed in covalent or molecular crystals overwhelmingly above ≈10 GPa, and the approaches to lower the transition pressure are limited on external heat‐treatment and/or catalyzers. Herein we demonstrate that, by internal‐lattice stress‐transfer from ionic to covalent groups, the transformation can be significantly prompted, as shown in a crystal of LiBO2 under 2.85 GPa for the first case in ionic crystals. This unprecedentedly low transformation pressure is ascribed to the enhanced localized stress on covalent B−O frames transferred from ionic Li−O bonds in LiBO2, and accordingly the corresponding structural feature is summarized. This work provides an internal structural regulation strategy for pressure‐reduction of the s‐p orbital hybridization transformation and extends the sp1/sp2‐to‐sp3 transformation landscape from molecular and covalent compounds to ionic systems.
3D Blockage Mapping for Identifying Familial Point Mutations in Single Amyloid‐β Peptides with a Nanopore
Authors: Xin Kai‐Li , Hu Zheng‐Li , Liu Shao‐Chuang , Li Xin‐Yi , Li Jun‐Ge , Niu Hongyan , Ying Yi‐Lun , Long Yi‐Tao
Published: September 2022

Accurate discrimination of amyloid‐β (Aβ) peptides containing familial point mutations would advance the knowledge of their roles in early‐onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild‐type (WT) Aβ18–26 peptides with aerolysin nanopore using a 3D blockage mapping strategy. The standard deviation of current blockade fluctuations (σb) was proposed as a new supplement to current blockage (Ib/I0) and duration time (tD) to profile the blockage characteristics of single molecules. Although the WT and A21G Aβ18‐26 are indistinguishable in a traditional Ib/I0‐tD 2D description, ∼87 % of the blockade events can be accurately classified with half reduction of false identification using a combination of Ib/I0, tD, and σb. This work offers an easy and reliable strategy to promote nanopore sensitivity of peptide mutants, leading to a more precise analysis of pathogenic mutations for developing effective diagnosis and treatment.
Targeted Singlet Oxygen Delivery: A Bioorthogonal Metabolic Shunt Linking Hypoxia to Fast Singlet Oxygen Release
Authors: Wu Hao , Wang Lei , Wang Yang , Shao Yujie , Li Guangzhe , Shao Kun , Akkaya Engin U.
Published: September 2022

Singlet oxygen can be generated by thermal cycloreversion of aromatic endoperoxides. However, for any practical potential of chemically generated singlet oxygen within a therapeutic context, the time and place of the release of this cytotoxic species must be tightly regulated. We now show that using a bimodular design with a hypoxia responsive unit and fluoride‐triggered endoperoxide unit, a bioorthogonal metabolic shunt can be established, where an enzymatically generated submicromolar fluoride signal plays a crucial role. Thus, cellular nitroreductase is repurposed in a bioorthogonal enzymatic activity, where it releases fluoride ions upon the reduction of a targeted compound. The fluoride ions released in the initial reaction remove the silyl stopper, yielding a highly accelerated release of singlet oxygen. The result is a remarkable difference in cytotoxicity between hypoxic and normoxic conditions as evidenced by microscopy, viability assays and the use of control compounds.
Temperature‐Controlled Mechanochemistry for the Nickel‐Catalyzed Suzuki–Miyaura‐Type Coupling of Aryl Sulfamates via Ball Milling and Twin‐Screw Extrusion.**
Authors: Bolt Robert R. A. , Raby‐Buck Sarah E. , Ingram Katharine , Leitch Jamie A. , Browne Duncan L.
Published: September 2022

The use of temperature‐controlled mechanochemistry to enable the mechanochemical nickel‐catalyzed Suzuki–Miyaura coupling is herein described. Transitioning from a capricious room‐temperature protocol, through to a heated, PID‐controlled programmable jar heater manifold was required to deliver an efficient method for the coupling of aryl sulfamates (derived from ubiquitous phenols) and aryl boronic acid species. Furthermore, this process is conducted using a base‐metal nickel catalyst, in the absence of bulk solvent, and in the absence of air/moisture sensitive reaction set‐ups. This methodology is showcased through translation to large‐scale twin‐screw extrusion methodology enabling 200‐fold scale increase, producing decagram quantities of C−C coupled material.
Ti‐doped CeO2 Stabilized Single‐Atom Rhodium Catalyst for Selective and Stable CO2 Hydrogenation to Ethanol
Authors: Zheng Ke , Li Yufeng , Liu Bing , Jiang Feng , Xu Yuebing , Liu Xiaohao
Published: September 2022

Development of effective and stable catalysts for CO2 hydrogenation into ethanol remains a challenge. Herein, we report that Rh1/CeTiOx single‐atom catalyst constructed by embedding monoatomic Rh onto Ti‐doped CeO2 support has shown a super high ethanol selectivity (≈99.1 %), record‐breaking turnover frequency (493.1 h−1), and outstanding stability. Synergistic effects of Ti‐doption and monoatomic Rh contribute to this excellent catalytic performance by firstly facilitating oxygen vacancies formation to generate oxygen‐vacancy‐Rh Lewis‐acid‐base pairs, which favor CO2 adsorption and activation, cleavage of C−O bonds in CHxOH* and COOH* into CHx* and CO* species, subsequent C−C coupling and hydrogenation into ethanol, and secondly generating strong Rh−O bond by Ti‐doping‐induced crystal reconstruction, which contributes to striking stability. This work highlights the importance of support elaborating regulation for single‐atom catalyst design to substantially improve the catalytic performance.
Regioselective Access to Vicinal Diamines by Metal‐Free Photosensitized Amidylimination of Alkenes with Oxime Esters
Authors: Zheng Yu , Wang Zhu‐Jun , Ye Zhi‐Peng , Tang Kai , Xie Zhen‐Zhen , Xiao Jun‐An , Xiang Hao‐Yue , Chen Kai , Chen Xiao‐Qing , Yang Hua
Published: September 2022

A metal‐free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional diamination reagent, thus affording a range of differentially protected 1,2‐diamines in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with a triplet‐triplet energy transfer between thioxanthone catalyst and diamination reagent, followed by fragmentation to simultaneously generate long‐lived iminyl radical and transient amidyl radical. The excellent regioselectivity presumably stems from the large reactivity difference between two different N‐centered radical species. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility of facilitate the diversity‐oriented synthesis of 1,2‐diamine‐containing complex molecule scaffolds.
Conferring BiVO4 Nanorods with Oxygen Vacancies to Realize Enhanced Sonodynamic Cancer Therapy
Authors: Yang Zhuang , Yuan Meng , Liu Bin , Zhang Wenying , Maleki Aziz , Guo Baolin , Ma Ping'an , Cheng Ziyong , Lin Jun
Published: September 2022

Owing to the high depth of tissue penetration, non‐invasiveness, and controllability, ultrasound (US)‐mediated sonodynamic therapy (SDT) has shown broad application prospects for tumor treatment. However, the electron‐hole separation inefficiency of sonosensitizers and the tumor hypoxia remain two major challenges limiting the effect of SDT. Here, ultrafine photoetched bismuth vanadate (BiVO4) nanorods modified with DSPE‐PEG2000 (PEBVO@PEG NRs) were fabricated to achieve in situ self‐supply of oxygen (O2) and reactive oxygen species (ROS) for hypoxic tumor therapy. The photoetching approach could enhance the charge separation by inducing enriched oxygen vacancies on the surface of BiVO4, thereby improving the generation efficiency of ROS and O2. The PEBVO@PEG overcome the main obstacles of traditional sonosensitizers in the SDT process and show promising sonodynamic therapeutic effects, thus providing new strategies for improving the performance of sonosensitizer and hypoxic tumor elimination.
Programmable Assembly of Multivalent DNA‐Protein Superstructures for Tumor Imaging and Targeted Therapy
Authors: Xu Zhen , Shi Tianhui , Mo Fengye , Yu Wenqian , Shen Yu , Jiang Qunying , Wang Fuan , Liu Xiaoqing
Published: September 2022

Programmable DNA materials hold great potential in biochemical and biomedical researches, yet the complicated synthesis, and the low stability and targeting efficacy in complex biological milieu limit their clinical translations. Here we show a one‐pot assembly of DNA‐protein superstructures as drug vehicles with specifically high affinity and stability for targeted therapy. This is achieved by biomimetic assembly of programmable polymer DNA wire into densely packed DNA nanosphere with an alkaline protein, protamine. Multivalent DNA nanostructures encoded with different types and densities of aptamers exhibit high affinity to targeted cells through polyvalent interaction. Our results show high cancer cell selectivity, reduced side effect, excellent therapeutic efficacy, and sensitive tumor imaging in both subcutaneous and orthotopic non‐small‐cell lung cancer murine models. This biomimetic assembly approach provides practical DNA nanomaterials for further clinical trials and may advance oligonucleotide drug delivery.
Pt Atoms/Clusters on Ni‐phytate‐sensitized Carbon Nitride for Enhanced NIR‐light‐driven Overall Water Splitting beyond 800 nm
Authors: Huang Yuanyong , Li Di , Feng Shuo , Jia Yujing , Guo Shuhui , Wu Xiaojie , Chen Min , Shi Weidong
Published: September 2022

Near‐infrared (NIR) light‐driven overall water splitting beyond 800 nm remains a high‐priority target yet great challenge. Here we report that efficient utilization of photogenerated electrons in a photosensitized system prepared by site‐selective photodeposition of platinum single atoms/clusters (Pt‐SACs) on Ni‐phytate (PA‐Ni)‐sensitized polymeric carbon nitride (PCN). The optimal catalyst presents simultaneous hydrogen (H2) and oxygen (O2) evolution with an H2evolution amount of 1.4 μmol at λ>800 nm for 24 hours, which its activity was approximately 140 times higher than that of a system without Pt‐SAC modification (PA‐Ni1.1@PCN). This work represents the first NIR‐light responsive photosensitized system for overall water splitting, and may open an avenue for precisely manipulating cocatalyst positions at the atomic level to improve NIR‐light‐driven overall water splitting via photosensitization.
Toxicity of Ocimum americanum L. extracts against Aedes aegypti larvae (Diptera: Culicidae) and their impact on insecticide resistance
Authors: Ramachandran Maduraiveeran , Deepika Nagabushanam , Jayakumar Manickkam
Published: September 2022

Mosquitoes are a key threat to millions of people worldwide. They spread the pathogens that cause deadly diseases among humans and animals. Synthetic pesticides are the best agents to control mosquitoes, but they cause several problems for the environment as well as public health. Continuous usage of commonly available insecticides develops multiple resistances among pests. In search of alternatives to synthetic pesticides, botanicals could be one of the best alternatives to control mosquitoes. The present study explores the insecticidal activity of Ocimum americanum against Aedes aegypti larvae and their effect on detoxification enzymes. Leaves of O. americanum were sequentially extracted using hexane, chloroform, and methanol. Among these, hexane extract showed 100% larvicidal activity at 1 g/L concentration for 24 h and the LC50 value was 0.3 g/L. The phytochemical screening of hexane extract was performed through gas chromatography‐mass spectrometry analysis, which showed 27 compounds. The major compounds are squalene (13.03%), camphor (9.77%), and 1‐Iodohexadecane (8.02%). The toxicity of active hexane extract was tested against third instar larvae of Chironomus costatus (nontarget organism). Results revealed less toxicity (12.2%) at 1 g/L concentration on the nontarget organism. The enzyme activity of acetylcholinesterase and β‐carboxylesterase was significantly inhibited by the hexane extract. The present study reveals the insecticidal potential of O. americanum with minimum effects on nontarget organisms. The O. americanum extract inhibited the activity of A. aegypti's major insecticide‐resistant enzymes. O. americanum could be one of the best alternatives to controlling mosquitoes.
Vanadium Redox Flow Battery Using Activated Carbon Catalyst Produced from Low‐Density Polyethylene
Authors: Lim Hyeonsoo , Shin Mingyu , Phae Chae‐Gun , Kwon Yongchai
Published: September 2022

Carbonized and activated low‐density polyethylene (LDPE) is suggested as a carbon catalyst for vanadium redox flow battery (VRFB). This carbon catalyst has many surface oxygen functional groups and a large surface area, while such benefits are achieved through activation of carbonized LDPE. According to electrochemical analysis, this carbon catalyst doped graphite felt (GF) enhances the redox reactivity of vanadium ions. More specifically, peak current density and peak potential separation for redox reaction of vanadium ions are 96.0 and 22.1% more improved than those measured by bare GF, while charge transfer resistance for the redox reactions is also improved by use of the catalyst doped GF. When performance of VRFB using this catalyst doped GF is measured, energy efficiency is 39% more improved than that measured without the catalyst. Based on that, this is revealed that new LDPE‐based carbon catalyst is effective for performance improvement of VRFB.
A rapid and sensitive UPLC–MS/MS method for the determination of zanubrutinib in beagle plasma and its application in pharmacokinetics
Authors: Zhu Yong‐liang , Ding Hao‐zhe , Gou Kai‐feng , Sun Bo , Chen Ye , Zhang He‐wei
Published: September 2022

A reliable and sensitive ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for the determination of zanubrutinib in the plasma of beagle dogs. The column used was an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm), maintained at 40°C with an injection volume of 2 μl. The gradient elution program was as follows: 0–1 min, 10–10% A; 1–1.1 min, 10–90% A; 1.1–2.1 min, 90–90% A; 2.1–2.2 min, 90–10% A; 2.2–3.0 min, 10–10% A. Mobile phase A was 0.1% formic acid, B was acetonitrile, and the total analysis time was 3 min. The mass spectrometry was performed in positive ion mode, and the scanning mode was multi‐reaction monitoring mode with electrospray ionization as the ion source; m/z 472.2 → 455.01 for zanubrutinib and m/z 441.03 → 137.99 for ibrutinib (internal standard). The plasma samples were processed by protein precipitation. The standard curve showed good linearity (r2 = 0.999 8) in the range of 1.0–1,000 ng/ml (zanubrutinib) with a low limit of quantification of 1 ng/ml. Also, the intra‐day and inter‐day precision (RSD) was <5.88% and the accuracy (RE) ranged from −1.56 to 1.08%; the recoveries of zanubrutinib in beagle plasma ranged from 90.12 to 93.53% (RSD 1.67–6.42%) and the ME values of zanubrutinib were 98.70–101.06% (RSD 5.37–8.49%, n = 6). All values meet US Food and Drug Administration requirements. A rapid, highly selective and sensitive method for the determination of zanubrutinib concentration in plasma by UPLC–MS/MS was successfully developed. This method is suitable for pharmacokinetic studies in beagle dogs by following oral administration of zanubrutinib.
Analysis of serum metabolism in premature infants before and after feeding using GC–MS and the relationship with necrotizing enterocolitis
Authors: Wang Fusheng , Wang Guanghuan , Li Weizhong , Xu Chenbin , Zeng Zailin , Zhou Yongcui
Published: September 2022

Preterm birth and enteral feeding are two main factors leading to necrotizing enterocolitis (NEC). The metabolomics of preterm infants before and after feeding can provide a basis for the prediction of NEC. Using the method of cross‐sectional study, the mode was established with the serum samples of 19 premature infants at birth and after feeding as the control group. The serum was analyzed using GC–MS. Chemometric analysis includes principal component analysis, partial least squares‐discriminant analysis, and orthogonal partial least squares‐discriminant analysis. Spectral separation of serum metabolites occurred in premature infants before and after feeding. The levels of xylose, d‐talose, phosphoglycolic acid, maleimide, l‐gulonolactone, maleic acid, β‐hydroxypyruvate, itaconic acid, and pantothenic acid in the serum of premature infants after feeding were significant in both multidimensional and single‐dimensional modes (variable importance in projection >2, P < 0.01). There was a moderate correlation between total bilirubin and l‐gulonolactone and β‐hydroxypyruvate (0.8 > r > 0.5). Maleimide, maleic acid, and itaconic acid have diagnostic value (area under the curve >0.9). The results indicated that serum metabolism of preterm infants changes significantly after feeding. Some metabolites have potential value in predicting NEC.
Knowledge and innovation management in agribusiness: A study in the Dominican Republic
Authors: Ureña‐Espaillat Hayrold José , Briones‐Peñalver Antonio Juan , Bernal‐Conesa Juan Andrés , Córdoba‐Pachón José Rodrigo
Published: September 2022

To date and worldwide, most business activities in the agribusiness sectors have focused on increasing productive efficiency to the detriment of the environmental impact of these activities, despite close connection that exist between agribusinesses and natural resources. This paper argues that knowledge and innovation management (KIM) can play a key role in fostering and managing creativity in the agribusiness sector. To test this assumption, an empirical model linking KIM with employee creativity, responsible green innovation, and performance in the agribusiness sector of the Dominican Republic is proposed and tested with data from 110 agribusiness companies. We found that strengthening the relationships between the above constructs is needed, with a view to readjusting the meaning of firm performance in the light of emerging (post‐pandemic) circumstances for agribusinesses. The statistical analyses yield important implications and recommendations for practice, management, and policy making in these areas in this country and elsewhere.
Does children’s fear matter? Evaluating children’s positions in Finnish court decisions on stalking
Authors: Koulu Sanna , Nikupeteri Anna , Laitinen Merja , Lohiniva‐Kerkelä Mirva
Published: September 2022

Children are at particular risk when one parent is targeted by the other parent's stalking behaviors post‐separation. In this article, we explore how court decisions position children when assessing fear, distress, and unlawfulness in cases of parental stalking. The data comprised 127 court decisions on stalking that involved a relationship (dating, cohabitation, or marriage), separation/divorce, and one or more children. Using discourse analysis, we identified four categories in how children were positioned: (1) children relegated to the background, (2) children’s involvement recounted as part of the facts, (3) children’s involvement assessed as relevant because it affected the parent, and (4) children as agents or victims in their own right. The findings highlight a significant risk of losing sight of children when the focus is on parents, and our concern is that this may also contribute to children not receiving the support they need.
Superoxide Dismutase 1 Folding Stability as a Target for Molecular Tweezers in SOD1‐Related Amyotrophic Lateral Sclerosis
Authors: Samanta Nirnay , Ruiz‐Blanco Yasser B. , Fetahaj Zamira , Gnutt David , Lantz Carter , Loo Joseph A. , Sanchez‐Garcia Elsa , Ebbinghaus Simon
Published: September 2022

Protein misfolding and aggregation are hallmarks of many severe neurodegenerative diseases including Alzheimer's, Parkinson's and Huntington's disease. As a supramolecular ligand that binds to lysine and arginine residues, the molecular tweezer CLR01 was found to modify the aggregation pathway of disease‐relevant proteins in vitro and in vivo with beneficial effects on toxicity. However, the molecular mechanisms of how tweezers exert these effects remain mainly unknown, hampering further drug development. Here, we investigate the modulation mechanism of unfolding and aggregation pathways of SOD1, which are involved in amyotrophic lateral sclerosis (ALS), by CLR01. Using a truncated version of the wildtype SOD1 protein, SOD1bar, we show that CLR01 acts on the first step of the aggregation pathway, the unfolding of the SOD1 monomer. CLR01 increases, by ∼10 °C, the melting temperatures of the A4V and G41D SOD1 mutants, which are commonly observed mutations in familial ALS. Molecular dynamics simulations and binding free energy calculations as well as native mass spectrometry and mutational studies allowed us to identify K61 and K92 as binding sites for the tweezers to mediate the stability increase. The data suggest that the modulation of SOD1 conformational stability is a promising target for future developments of supramolecular ligands against neurodegenerative diseases.
Exploiting the Innate Plasticity of the Programmed Cell Death‐1 (PD1) Receptor to Design Pembrolizumab H3 Loop Mimics**
Authors: Richaud Alexis D. , Zaghouani Mehdi , Zhao Guangkuan , Wangpaichitr Medhi , Savaraj Niramol , Roche Stéphane P.
Published: September 2022

Checkpoint blockade of the immunoreceptor programmed cell death‐1 (PD1) with its ligand‐1 (PDL1) by monoclonal antibodies such as pembrolizumab provided compelling clinical results in various cancer types, yet the molecular mechanism by which this drug blocks the PD1/PDL1 interface remains unclear. To address this question, we examined the conformational motion of PD1 associated with the binding of pembrolizumab. Our results revealed that the innate plasticity of both C'D and FG loops is crucial to form a deep binding groove (371 Å3) across several distant epitopes of PD1. This analysis ultimately provided a rational‐design to create pembrolizumab H3 loop mimics [RDYRFDMGFD] into β‐hairpin scaffolds. As a result, a 20‐residue long β‐hairpin peptide 1 e was identified as a first‐in‐class potent PD1‐inhibitor (EC50 of 0.29 μM; Ki of 41 nM).
Pseudoxanthomatous salpingitis: An uncommon lesion of the fallopian tube
Authors: Limaiem Faten , Halouani Ahmed , Dimassi Kaouther
Published: September 2022

Pseudoxanthomatous salpingitis (PXS) is an uncommon condition characterized by the presence of pigment‐laden histiocytes within the lamina propria of the fallopian tube. Less than 30 cases of PXS have been reported in the literature. We herein report a case of PXS associated with an endometriotic cyst.
Imine Reductases: Multifunctional Biocatalysts with Varying Active Sites and Catalytic Mechanisms
Authors: Wu Kai , Huang Junhai , Shao Lei
Published: September 2022

The synthesis of chiral amines is significant in the pharmaceutical industry. Imine reductase (IRED), a promising biocatalyst that was previously known to only catalyze asymmetric imine reduction (IR), was revealed to achieve direct asymmetric reductive amination (RA) of ketones with excess amines, producing secondary and tertiary amines. Moreover, conjugate reduction (CR) and RA activity by a single IRED has been reported for the preparation of valuable amine diastereomers. IREDs catalyzing these different reactions share the same standard quaternary structure, but possess varying active sites, indicating correlations and differences between their catalytic mechanisms. In this review, we trace the catalytic mechanisms reported for IRED‐catalyzed IR, RA, and CR‐RA. Insights obtained from structural and protein engineering in understanding the IRED‐catalyzed asymmetric synthesis are also included. This review will help readers acquire comprehensive insights into the catalytic mechanism of IREDs and ultimately inspire the engineering of IREDs for industrial applications.
Effect of Steaming on Waste‐Derived Zeolite ZSM‐5 as Methanol‐To‐Hydrocarbons Catalyst
Authors: Nikolopoulos Nikolaos , van Veenhuizen Oscar , Weckhuysen Bert Marc
Published: September 2022

The valorization of low‐grade industrial residues into valuable materials has been a way to reduce the impact of the industry on planetary boundaries. Silicon‐rich wastes have been used for zeolite synthesis while the impurities originating from wastes have a vital role in the physicochemical properties and the catalytic performance of waste‐derived zeolites. Here, the effect of steaming and the impact of impurities on waste‐derived zeolites were investigated. Steamed waste‐derived zeolite ZSM‐5 maintained their structure while their Brønsted acidity was decreased significantly due to dealumination. Electron paramagnetic resonance revealed that steaming of the samples resulted in the re‐dispersion of Fe impurities phases. The waste‐derived zeolites exhibited a high amount of weak and intermediate acidity upon steaming. Interestingly, the waste‐derived sample with a higher amount of impurities had an increase in Lewis acidity upon steaming, while catalytic testing in the Methanol‐to‐Hydrocarbons reaction exhibited 10 % higher conversion and 4 % in propylene yield.
Unprecedented Combination of Polyketide Natural Product Fragments Identifies the New Hedgehog Signaling Pathway Inhibitor Grismonone
Authors: Grigalunas Michael , Patil Sohan , Krzyzanowski Adrian , Pahl Axel , Flegel Jana , Schölermann Beate , Xie Jianing , Sievers Sonja , Ziegler Slava , Waldmann Herbert
Published: September 2022

Pseudo‐natural products (pseudo‐NPs) are de novo combinations of natural product (NP) fragments that define novel bioactive chemotypes. For their discovery, new design principles are being sought. Previously, pseudo‐NPs were synthesized by the combination of fragments originating from biosynthetically unrelated NPs to guarantee structural novelty and novel bioactivity. We report the combination of fragments from biosynthetically related NPs in novel arrangements to yield a novel chemotype with activity not shared by the guiding fragments. We describe the synthesis of the polyketide pseudo‐NP grismonone and identify it as a structurally novel and potent inhibitor of Hedgehog signaling. The insight that the de novo combination of fragments derived from biosynthetically related NPs may also yield new biologically relevant compound classes with unexpected bioactivity may be considered a chemical extension or diversion of existing biosynthetic pathways and greatly expands the opportunities for exploration of biologically relevant chemical space by means of the pseudo‐NP principle.
Trianionic 1,3,2‐Dioxaborine‐Containing Polymethines: Bright Near‐Infrared Fluorophores
Authors: Polishchuk Vladyslav , Filatova Mariia , Rusanov Eduard , Shandura Mykola
Published: September 2022

Trianionic polymethines of the A′‐π‐A‐π‐A‐π‐A′ type comprising dioxaborine rings (A) and different electron‐accepting end groups (A′) have been synthesized. The obtained dyes absorb and emit light in the near‐infrared region with remarkably high molar attenuation coefficients (ϵ up to 495 000 M−1 cm−1 in DMF) and fluorescence quantum yields (Φf up to 0.73 in DMF). Thus, the novel trianionic dyes stand among the brightest individual fluorophores known to date – with a magnitude of fluorescence brightness (ϵ⋅Φf) of 313 000 M−1 cm−1 in DMF. The synthesized dyes demonstrate a minor negative solvatochromism and small Stokes shifts. X‐ray data reveal the nearly planar geometry of the trianionic chromophore. All the obtained compounds are stable in the solid state and in a solution, although the relative stability is much higher in polar aprotic than in protic solvents.
Chemical Strategies for Dendritic Magneto‐plasmonic Nanostructures Applied to Surface‐Enhanced Raman Spectroscopy
Authors: Fernandes Tiago , Nogueira Helena I. S. , Amorim Carlos O. , Amaral João S. , Daniel‐da‐Silva Ana L. , Trindade Tito
Published: September 2022

Chemical analyses in the field using surface‐enhanced Raman scattering (SERS) protocols are expected to be part of several analytical procedures applied to water quality monitoring. To date, these endeavors have been supported by developments in SERS substrate nanofabrication, instrumentation portability, and the internet of things. Here, we report distinct chemical strategies for preparing magneto‐plasmonic (Fe3O4 : Au) colloids, which are relevant in the context of trace‐level detection of water contaminants due to their inherent multifunctionality. The main objective of this research is to investigate the role of poly(amidoamine) dendrimers (PAMAMs) in the preparation of SERS substrates integrating both functionalities into single nanostructures. Three chemical routes were investigated to design magneto‐plasmonic nanostructures that translate into different ways for assessing SERS detection by using distinct interfaces. Hence, a series of magneto‐plasmonic colloids have been characterized and then assessed for their SERS activity by using a model pesticide (thiram) dissolved in aqueous samples.
Highly Active La(III)‐Based Metal‐Organic Framework as a Heterogeneous Lewis Acid Catalyst for Friedel‐Crafts Alkylation
Authors: Wu Jia‐Qi , Wu Xin‐Yuan , Lu Jian‐Mei , Shi Qian , Shao Li‐Xiong
Published: September 2022

In this study, a novel La(III)‐based two‐dimensional (2D) metal‐organic framework, [La2/3(qptca)1/2] (referred to as SLX‐2), from LaCl3 and 1,1′ : 4′,1′′ : 4′′,1′′′ : 4′′′,1′′′′‐quinquephenyl]‐2,2′′,2′′′′,5′′‐tetracarboxylic acid (H4qptca) was synthesized by conventional solvothermal method and thoroughly characterized by using X‐ray single‐crystal diffraction, powder X‐ray diffraction, and thermogravimetric analyses. The 2D SLX‐2 features a unique lanthanum center exposed to the skeleton and was used as an efficient Lewis acid catalyst for the Friedel‐Crafts alkylation of indole and pyrrole with β‐nitrostyrene along with a wide substrate scope, giving the desired products in good‐to‐high yields under the optimal reaction conditions. Furthermore, the catalyst was used for twenty cycles, with nearly no effect on its activity, and the reaction was heterogeneous in nature. Moreover, compared to the previous hydrogen‐bond‐donating MOF catalysts for such alkylation reactions, SLX‐2 showed an excellent stability toward harsh acidic and basic environment, and gave comparable catalytic activities.
Synthesis of Cyclic and Acyclicortho‐Aryloxy Diaryliodonium Salts for Chemoselective Functionalizations
Authors: Linde Erika , Knippenberg Niels , Olofsson Berit
Published: September 2022

Two regioselective, high‐yielding one‐pot routes to oxygen‐bridged cyclic diaryliodonium salts andortho‐aryloxy‐substituted acyclic diaryliodonium salts are presented. Starting from easily availableortho‐iodo diaryl ethers, complete selectivity in formation of either the cyclic or acyclic product could be achieved by varying the reaction conditions. The complimentary reactivities of these novel ortho‐oxygenated iodonium salts were demonstrated through a series of chemoselective arylations under metal‐catalyzed and metal‐free conditions, to deliver a range of novel,ortho‐functionalized diaryl ether derivatives.
A Photochemical Macrocyclization Route to Asymmetric Strained [3.2] Paracyclophanes
Authors: Haensch Veit G. , Görls Helmar , Hertweck Christian
Published: September 2022

The intricate frameworks of paracyclophanes are an important target for synthesis since they are found in various chiral auxiliaries, solar cells, high‐performance plastics, pharmaceuticals, and molecular machines. Whereas numerous methods exist for the preparation of symmetric paracyclophanes, protocols for the efficient synthesis of strained asymmetric scaffolds are limited. Here we report a remarkably simple photochemical route to strained [3.2]paracyclophanes starting from readily available educts. By way of NMR and X‐ray analyses, we discovered that UV‐irradiation of an aromatic carboxylic ester tethered to a toluene moiety leads to the intramolecular formation of a new C−C bond, with loss of an alcohol. A systematic evaluation of the reaction conditions and substituents, as well as radical starter and triplet quenching experiments, point to a reaction mechanism involving an excited triplet state and hydrogen atom transfer. The new method proved to be robust and versatile enabling the synthesis of a range of cyclophanes with different substitutions, including an unusual diastereoisomer with two planar chiral centers, and thus proved to be a valuable addition to the synthetic toolbox.
Synthesis of meso‐Free Decaphyrin(1.1.1.1.1.1.1.1.1.1) by a Hydrodebromination Protocol; Aromaticity and Solvent‐Polarity Dependent Conformational Change
Authors: Nakai Akito , Saito Hayate , Yorimitsu Hideki , Tanaka Takayuki , Osuka Atsuhiro
Published: September 2022

A meso‐free β‐bromodecaphyrin has been constructed by [2+3+2+3] type acid‐catalyzed cross‐condensation and subsequent oxidation. Hydrodebromination of this tetrabromodecaphyrin with NaBH4 in the presence of TMEDA and palladium catalyst afforded β‐unsubstituted doubly meso‐free [46]decaphyrin(1.1.1.1.1.1.1.1.1.1) as the first example of β‐unsubstituted meso‐free regular expanded porphyrins with the number of pyrrole units larger than eight. It exhibits distinct aromaticity originating from its 46π‐conjugated electronic circuit and flexible conformational change between non‐twisted and doubly twisted forms depending on the solvent‐polarity. Their distinct conformations have been analyzed by combined experimental and theoretical investigations.
Intense Molar Circular Dichroism in Fully Conjugated All‐Carbon Macrocyclic 1,3‐Butadiyne Linked pseudo‐meta [2.2]Paracyclophanes
Authors: Sidler Eric , Zwick Patrick , Kress Charlotte , Reznikova Ksenia , Fuhr Olaf , Fenske Dieter , Mayor Marcel
Published: September 2022

Invited for the cover of this issue is the group of Marcel Mayor at the University of Basel with co‐workers Olaf Fuhr and Dieter Fenske from Karlsruhe Institute of Technology. The image depicts the studied all‐carbon polygon shaped macrocycles along with their intense circular dichroism spectra in the background. The bright light within the macrocycles displays its efficient conjugation. Read the full text of the article at 10.1002/chem.202201764.
Photo‐triggered Intramolecular Radical Tandem Regioselective Alkylation/Cyclization of 1,6‐Dienes with Redox‐Active Esters Enabled by an EDA Complex
Authors: Sun Bin , Ling Lan , Zhuang Xiaohui , Yang Lulu , Yin Jieli , Jin Can
Published: September 2022

Comprehensive Summary

A photocatalyst‐ and metal‐free radical tandem alkylation/cyclization between 1,6‐dienes and redox‐active esters has been developed, affording a series of N‐aryl pyrrolidine‐2‐ones in moderate to good yields. The transformation is driven by the formation of an electron‐donor‐acceptor (EDA) complex and a subsequent single electron transfer (SET) process. This photocatalyst‐free protocol features excellent regioselectivity, mild conditions and broad substrate scope, providing a facile access to 3‐alkyl‐3,4‐dimethyl‐1‐phenylpyrrolidin‐2‐one.
Drug Discovery and Development on Pma1, Where Are We Now? A Critical Review from 1995 to 2022
Authors: Tung Truong‐Thanh , Nielsen John
Published: September 2022

Plasma membrane H+‐ATPase (Pma1) is an enzyme uniquely found in plants and fungi. The enzyme controls the nutrient uptake of plants and fungi via an electrochemical gradient processes, which is essential for their survival. Inhibiting Pma1, therefore, constitutes an alternative antifungal target void of toxicity to humans. From a medicinal chemistry point of view, this review provides a first summary of the recent drug design, synthesis, evaluation, and discovery of molecules targeting Pma1 for 25 years from 1995 to 2022.