bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric binding of the primary acceptor quinone in reaction centers of the photosynthetic bacterium Rhodobacter sphaeroides R26, probed with Q‐band (35 GHz) EPR spectroscopy
Authors: van den Brink Johan S. , Spoyalov Andrej P. , Gast Peter , van Liemt Willem B.S. , Raap Jan , Lugtenburg Johan , Hoff Arnold J.
Published: July 2002

The reaction center (RC)‐bound primary acceptor quinone QA of the photosynthetic bacterium Rhodobacter sphaeroides R26 functions as a one‐electron gate. The radical anion Q•−
A is proposed to have an asymmetric electron distribution, induced by the protein environment. We replace the native ubiquinone‐10 (UQ10) with specifically 13C‐labelled UQ10, and use Q‐band (35 GHz) EPR spectroscopy to investigate this phenomenon in closer detail. The direct observation of the 13C‐hyperfine splitting of the g
z‐component of UQ10•−
A in the RC and in frozen isopropanol shows that the electron spin distribution is symmetric in the isopropanol glass, and asymmetric in the RC. Our results allow qualitative assessment of the spin and charge distribution for Q•−
A in the RC. The carbonyl oxygen of the semiquinone anion nearest to the S = 2 Fe2+‐ion and QB is shown to acquire the highest (negative) charge density.
Famotidine: a supplemental drug for the treatment of schizophrenia
Authors: Dannon PN , Lepkifker E , Iancu I , Ziv R , Horesh N , Kotler M
Published: July 2002

In an open-label study, famotidine was added to the regular neuroleptic regimen of 11 schizophrenic patients for 4 weeks. Each patient was scored weekly with SAPS, SANS, CGI and HAM-D-17 scales. The results suggest that famotidine is indeed effective as an adjunctive drug to neuroleptics in the treatment of schizophrenia.
Responsiveness of observer rating scales by analysis of number of days until improvement in patients with major depression
Authors: Lauge N , Behnke K , Søgaard J , Bahr B , Bech P
Published: July 2002

Several well-known observer scales, including the Hamilton Depression Scale (HAM-D), Montgomery-Åsberg Scale (MADRS), Major Depression Rating Scale (MDS), Melancholia Scale (MES), and Inventory for Depressive Symptomatology (IDS) used for measuring severity of depressive states have been compared by their responsiveness in an open trial including patients treated with a combination of citalopram and mianserin. The patients fulfilled the Diagnostic and Statistical Manual (DSM)-IV criteria for major depressive episode, and all scored 18 or more on the HAM-D before treatment. Onset of antidepressant action was defined as an improvement of rating scale scores of 25% or more of pre-treatment scores. A response to treatment was defined as a reduction of 50% or more on the pre-treatment scores. The results showed that the number of treatment days until improvement was 11 to 13 with no difference between the scales. The days until response were between 18 and 21 with no difference between the scales. In conclusion, the depression scales were found to be equal in their ability to detect changes in depressive symptoms during treatment. The mean of days to response was 19 for the combination of citalopram and mianserin. This is similar to the response for the combination of fluoxetine and pinolol.
Multi‐kinase framework promotes proliferation and invasion of lung adenocarcinoma through activation of dynamin‐related protein 1
Authors: Chung Kuei‐Pin , Huang Yen‐Lin , Chen Yi‐Jung , Juan Yi‐Hsiu , Hsu Chia‐Lang , Nakahira Kiichi , Huang Yen‐Tsung , Lin Mong‐Wei , Wu Shang‐Gin , Shih Jin‐Yuan , Chang Yih‐Leong , Yu Chong‐Jen
Published: November 2020

Recent studies revealed the role of dynamin‐related protein 1 (DRP1), encoded by the DNM1L gene, in regulating the growth of cancer cells of various origins. However, the regulation, function, and clinical significance of DRP1 remain undetermined in lung adenocarcinoma. Our study shows that the expression and activation of DRP1 are significantly correlated with proliferation and disease extent, as well as an increased risk of postoperative recurrence in stage I to stage IIIA lung adenocarcinoma. Loss of DRP1 in lung adenocarcinoma cell lines leads to an altered mitochondrial morphology, fewer copies of mitochondrial DNA, decreased respiratory complexes, and impaired oxidative phosphorylation. Additionally, the proliferation and invasion are both suppressed in DRP1‐depleted lung adenocarcinoma cell lines. Our data further revealed that DRP1 activation through serine 616 phosphorylation is regulated by ERK/AKT and CDK2 in lung adenocarcinoma cell lines. Collectively, we propose the multikinase framework in activating DRP1 in lung adenocarcinoma to promote the malignant properties. Biomarkers related to mitochondrial reprogramming, such as DRP1, can be used to evaluate the risk of postoperative recurrence in early‐stage lung adenocarcinoma.
Scale Banking for Patient‐Reported Outcome Measures That Measure Functioning in Rheumatoid Arthritis: A Daily Activities Metric
Authors: Prodinger Birgit , Coenen Michaela , Hammond Alison , Küçükdeveci Ayşe A. , Tennant Alan
Published: November 2020

Objective

Functioning is an important outcome for the management of rheumatoid arthritis (RA). Heterogeneity of respective patient‐reported outcome measures (PROMs) challenges direct comparisons between their results. This study aimed to standardize reporting of such PROMs measuring functioning in RA to facilitate comparability.

Methods

Common‐item nonequivalent group design with the Health Assessment Questionnaire (HAQ) as a common scale across data sets from various countries (including the UK, Turkey, and Germany) to establish a common metric was used. Other PROMs included are the physical function items of the Multidimensional HAQ (MDHAQ), the Disabilities of the Arm, Shoulder, and Hand questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the World Health Organization Disability Assessment Schedule II (WHODAS II), the Medical Outcomes Study Short Form 36 (SF‐36) health survey, and 4 short forms (20, 10, 6, and 4 physical function items) from the Patient‐Reported Outcomes Measurement Information System. As the HAQ includes mobility, self‐care, and domestic life items, this study focuses on these 3 domains. PROMs were described using standard error of measurement (SEM) and smallest detectable difference (SDD). A Rasch measurement model was used to create the common metric.

Results

The range of the SEM was 0.2 (MDHAQ) to 7.4 (SF‐36 health survey physical functioning domain). The SDD revealed a range from 9.7% (WOMAC rating scale) to 33.5% (WHODAS physical functioning domain). PROMs co‐calibration revealed fit to the Rasch measurement model. A transformation table was developed to allow exchange between PROM scores.

Conclusion

Scores between the daily activity PROMs commonly used in RA can now be compared. Factors such as SEM and SDD help to determine the choice of a PROM in clinical practice and research.
Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications
Authors: Song Nan , Zhang Zhijun , Liu Peiying , Yang Ying‐Wei , Wang Lei , Wang Dong , Tang Ben Zhong
Published: November 2020

One of the major pursuits of biomedical science is to develop advanced strategies for theranostics, which is expected to be an effective approach for achieving the transition from conventional medicine to precision medicine. Supramolecular assembly can serve as a powerful tool in the development of nanotheranostics with accurate imaging of tumors and real‐time monitoring of the therapeutic process upon the incorporation of aggregation‐induced emission (AIE) ability. AIE luminogens (AIEgens) will not only enable fluorescence imaging but will also aid in improving the efficacy of therapies. Furthermore, the fluorescent signals and therapeutic performance of these nanomaterials can be manipulated precisely owing to the reversible and stimuli‐responsive characteristics of the supramolecular systems. Inspired by rapid advances in this field, recent research conducted on nanotheranostics with the AIE effect based on supramolecular assembly is summarized. Here, three representative strategies for supramolecular nanomaterials are presented as follows: a) supramolecular self‐assembly of AIEgens, b) the loading of AIEgens within nanocarriers with supramolecular assembly, and c) supramolecular macrocycle‐guided assembly via host–guest interactions. Meanwhile, the diverse applications of such nanomaterials in diagnostics and therapeutics have also been discussed in detail. Finally, the challenges of this field are listed in this review.
Preferentially Engineering FeN4 Edge Sites onto Graphitic Nanosheets for Highly Active and Durable Oxygen Electrocatalysis in Rechargeable Zn–Air Batteries
Authors: Xiao Meiling , Xing Zihao , Jin Zhao , Liu Changpeng , Ge Junjie , Zhu Jianbing , Wang Ying , Zhao Xiao , Chen Zhongwei
Published: November 2020

Single‐atom FeN4 sites at the edges of carbon substrates are considered more active for oxygen electrocatalysis than those in plane; however, the conventional high‐temperature pyrolysis process does not allow for precisely engineering the location of the active site down to atomic level. Enlightened by theoretical prediction, herein, a self‐sacrificed templating approach is developed to obtain edge‐enriched FeN4 sites integrated in the highly graphitic nanosheet architecture. The in situ formed Fe clusters are intentionally introduced to catalyze the growth of graphitic carbon, induce porous structure formation, and most importantly, facilitate the preferential anchoring of FeN4 to its close approximation. Due to these attributes, the as‐resulted catalyst (denoted as Fe/N‐G‐SAC) demonstrates unprecedented catalytic activity and stability for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) by showing an impressive half‐wave potential of 0.89 V for the ORR and a small overpotential of 370 mV at 10 mA cm−2 for the OER. Moreover, the Fe/N‐G‐SAC cathode displays encouraging performance in a rechargeable Zn–air battery prototype with a low charge–discharge voltage gap of 0.78 V and long‐term cyclability for over 240 cycles, outperforming the noble metal benchmarks.
Synergistic Optimization Enables Large‐Area Flexible Organic Solar Cells to Maintain over 98% PCE of the Small‐Area Rigid Devices
Authors: Wang Guodong , Zhang Jianqi , Yang Chen , Wang Yuheng , Xing Yi , Adil Muhammad Abdullah , Yang Yang , Tian Lijun , Su Ming , Shang Wuqiang , Lu Kun , Shuai Zhigang , Wei Zhixiang
Published: November 2020

Slot‐die coating is generally regarded as the most effective large‐scale methodology for the fabrication of organic solar cells (OSCs). However, the corresponding device performance significantly lags behind spin‐coated devices. Herein, the active layer morphology, flexible substrate properties, and the processing temperature are optimized synergistically to obtain high power conversion efficiency (PCE) for both the flexible single cells and the modules. As a result, the 1 cm2 flexible devices produce an excellent PCE of 12.16% as compared to 12.37% for the spin‐coated small‐area (0.04 cm2) rigid devices. Likewise, for modules with an area of 25 cm2, an extraordinary PCE of 10.09% is observed. Hence, efficiency losses associated with the upscaling are significantly reduced by the synergistic optimization. Moreover, after 1000 bending cycles at a bending radius of 10 mm, the flexible devices still produce over 99% of their initial PCE, whereas after being stored for over 6000 h in a glove box, the PCE reaches 103% of its initial value, indicating excellent device flexibility as well as superior shelf stability. These results, thus, are a promising confirmation the great potential for upscaling of large‐area OSCs in the near future.
Nickel/Cobalt‐Catalyzed Reductive Hydrocyanation of Alkynes with Formamide as the Cyano Source, Dehydrant, Reductant, and Solvent
Authors: Zhang Jin , Luo Cui‐Ping , Yang Luo
Published: November 2020

A Ni/Co co‐catalyzed reductive hydrocyanation of various alkynes was developed for the production of saturated nitriles. Hydrocyanic acid is generated in situ from safe and readily available formamide. Formamide played multiple roles as a cyano source, dehydrant, and reductant for the NiII pre‐catalyst and vinyl nitriles, along with acting as the co‐solvent in this reaction. Detailed mechanistic investigation supported a pathway via hydrocyanation of C≡C bond and the subsequent reduction of C=C bond. Wide substrate scope, the employment of a cheap and stable nickel salt as pre‐catalyst, a safe cyano source and convenient experimental operation render this hydrocyanation practical for the laboratory synthesis of saturated nitriles.

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Family‐based Intervention for Legal System‐involved Girls: A Mixed Methods Evaluation
Authors: Anderson Valerie R. , Rubino Laura L. , McKenna Nicole C.
Published: November 2020

The increased proportion of juvenile court‐involved girls has spurred interest to implement and evaluate services to reduce girls’ system involvement. The purpose of this study was to examine the effectiveness of a family‐based intervention by using a dominant sequential mixed methods evaluation approach. First, we examined quantitative data using a quasi‐experimental design to determine whether the family‐based intervention reduced recidivism among court‐involved girls. Propensity score matching (PSM) was used to construct statistically equivalent groups to compare one‐year recidivism outcomes for girls who received the court‐run family‐based intervention (n = 181) to a group of girls on probation who did not receive the intervention (n = 803). Qualitative interviews (n = 39) were conducted to contextualize the quantitative findings and highlighted the circumstances that family‐focused interventions for court‐involved girls. Girls who received the program had slightly lower recidivism rates following the intervention. The qualitative findings contextualized the quasi‐experimental results by providing an explanation as to the girls’ family circumstances and insights into the mechanisms of the intervention. Results highlighted the importance of family‐focused interventions for juvenile justice‐involved girls. These findings have practical and policy implications for the use interventions—beyond the individual level—with adjudicated girls and offer suggestions for ways to improve their effectiveness using a community psychology lens. In addition, this paper includes a discussion of evaluating of juvenile court programming from a community psychology perspective including strengths, challenges, and considerations for future work in this area.
Infrared Laser Desorption and Electrospray Ionisation of Non‐Covalent Protein Complexes: Generation of Intact, Multiply Charged Species
Authors: Kooijman Pieter C. , Mathew Anjusha , Ellis Shane R. , Heeren Ron M. A.
Published: November 2020

We present a novel method enabling the infrared laser desorption and electrospray ionisation (ESI) of protein complexes in their native state. Using this method, we demonstrate the surprising generation of intact, multiply charged ions of myoglobin, non‐covalent haemoglobin complex, and intact immunoglobulin G antibody in their native states. The observation of a surviving population of intact non‐covalent complexes is characteristic of the low internal energy build‐up experienced during both laser desorption from solution and subsequent ionisation. Compared to conventional nano‐ESI, this approach yielded slightly lower average charge states suggesting additional maintenance of tertiary structure during desorption and ionisation, and is more tolerant to salts enabling simpler sample purification procedures. This approach may enable the development of high‐throughput native‐MS methods capable of analysing the composition and sequence of multiple macromolecular samples per minute.
Terpolymer with rigid side chain as filtrate reducer for water‐based drilling fluids
Authors: Li Pengpeng , Xu Yang , Liu Ying , Feng Jie , Hui Baotong , Feng Yakai , Hu Miaomiao , Guo Jintang
Published: November 2020

Synthetic copolymers as filtrate reducers for water‐based drilling fluids (WBDFs) are difficult to meet the needs of drilling engineering only by changing the type and proportion of functional groups of copolymers, especially under ultra‐high temperature and high salinity. In this study, an anionic terpolymer (named PSDI) with rigid side chain was synthesized using sodium p‐styrenesulfonate, N, N‐Dimethylacrylamide, and itaconic acid by free‐radical copolymerization. The chemical structure of PSDI was characterized by Fourier transform infrared spectroscopy and1H‐NMR spectrum. The high‐temperature/high‐pressure filtration loss (FLHTHP) and the American Petroleum Institute filtration loss (FLAPI) of the WBDFs containing 1.5 wt/vol% PSDI were 35.0 and 17.0 ml after thermal rolling at 240°C for 16 h, respectively. The FLHTHPand FLAPIof the WBDFs containing saturated NaCl were with control of 60.0 and 12.0 ml. The FLAPIof WBDFs containing 1.5 wt/vol% CaCl2reduced to 6.0 ml. Results indicate that the addition of PSDI can improve the anti‐high‐temperature performance and resistance to salt and calcium contamination of WBDFs. Results of rheological tests through fitting four rheological models suggest that rheological parameters can be improved as a result of forming the spatial network structure between the PSDI and bentonite flakes.
Solid–solid phase‐change materials cross‐linked by carbon quantum dots: Address leakage and high super‐cooling degree simultaneously
Authors: Wang Yuhang , Xiao Yao , Wu Bo , Lei Jingxin
Published: November 2020

Leakage and super‐cooling are two main disadvantages of polyethylene glycol (PEG) when used as phase‐change materials (PCMs) for thermal energy storage, which seriously restrict the practical applications of the materials. In this study, we employ carbon quantum dots (CQDs) as cross‐linkers to fabricate PEG‐based solid–solid PCMs, which not only address the leakage issue of PEG during melting process, but also have much lower super‐cooling degree compared with PEG, exhibiting extraordinary thermal energy storage performance. CQDs serve as a heterogeneous nucleating agent in the crystal domains of these PEG‐based PCMs according to the characterizations. Additionally, CQDs are also beneficial to the thermal stability of the PCMs. And these PEG‐based PCMs have high phase‐change enthalpies (94.4 J/g) and applicable phase‐change temperatures (25–37°C), showing potential for thermal energy storage.
Fluorocyclization of Vinyl Azides for the Formation of 3‐Azido Heterocycles
Authors: Bai Diangang , Li Linxuan , Li Xiaomeng , Lu Ying , Wu Yong , Rajendra Prasad Reddy Bhoomireddy , Ning Yongquan
Published: November 2020

3‐Azido saturated heterocycles are important for therapeutic‐development but challenging to prepare. Disclosed herein is a novel synthetic strategy for 3‐azido heterocycles via fluorocyclization of the easily available vinyl azides. This transfor‐mation proceeded under mild conditions and provided a wide range of 3‐azido heterocycles in good to excellent yields. Notably, the azido group plays an indispensable role to promote rapid and regioselective fluorocyclization. Moreover, the protocol was highlighted by gram‐scale synthesis and further synthetic transformations.
Different Role of Raptor and Rictor in Regulating Rasfonin‐Induced Autophagy and Apoptosis in Renal Carcinoma Cells
Authors: Hou Bolin , Liu Shuchun , Li Erwei , Jiang Xuejun
Published: November 2020

Both Raptor and Rictor are the key components in the complexes of mammalian target of rapamycin (mTOR), which play a vital role in mediating autophagy. Unlike mTOR, the regulatory role of either Raptor or Rictor in the regulation of autophagic process is relatively less explored. In present study, we found that rasfonin, which isolated from Talaromyces sp. 3656‐A1 and was a fungal natural product, activated both caspase‐dependent apoptosis and autophagy in ACHN, a renal carcinoma cell line. Knockdown of Raptor decreased both rasfonin‐induced autophagic flux and PARP‐1 cleavage, and in contrast, Rictor silencing increased apoptosis concomitantly enhancing rasfonin‐induced autophagy. Unexpectedly, API‐2, which was widely used as an inhibitor of Akt, promoted rasfonin‐dependent autophagy in Raptor‐depleted but not Rictor‐deprived cells. Collectively, these results demonstrated that Raptor and Rictor could play a distinctly regulatory role in rasfonin‐enhanced autophagy and apoptosis.
A rare case of synovial sarcoma presenting as abdominal pain
Authors: Pan Kelsey , Waheed Nida , Smith James M. , Zaidi Zareen
Published: November 2020

Abdominal pain can arise from numerous sources, including those extra‐abdominal. It is important to obtain additional imaging in the setting of clinical suspicion for malignancy.
Enhanced Electron Transfer and Ion Transport by Binary and Multidimensional CuCo2S4/Fe2O3 on Carbon Cloth for Water Oxidation
Authors: Lu Minglong , Zhang Xiaoyun , Tong Jiwei , Wang Wei , Wang Yuqiao
Published: November 2020

The behavior of electron transfer and ion transport plays a significant role in the electrocatalytic activity. However, the improvement of CuCo2S4 electrocatalytic activity has been a difficult problem owing to lack of effective electron transfer and ion transport. Herein, the unique structure connected CuCo2S4 nanosheets and carbon cloth (CC) with Fe2O3 nanoparticles to form CuCo2S4/Fe2O3/CC. Compared with CuCo2S4/CC, the resistances of electron transfer and ion transport were decreased by 65 and 84 %, respectively. The electrochemical surface area of CuCo2S4/Fe2O3/CC was 2.76 times larger than that of CuCo2S4/CC due to the high double‐layer capacitance. For the oxygen evolution reaction, CuCo2S4/Fe2O3/CC could achieve an overpotential of 273 mV and a Tafel slope of 67 mV dec−1 in alkaline solution.
Construction of Hybrid Bimetallic Uranyl Compounds Based on a Preassembled Terpyridine Metalloligand
Authors: Kong Xianghe , Hu Kongqiu , Mei Lei , Wu Qunyan , Huang Zhiwei , Liu Kang , Chai Zhifang , Nie Changming , Shi Weiqun
Published: November 2020

Six hybrid uranyl–transition metal compounds [UO2Ni(cptpy)2(HCOO)2(DMF)(H2O)] (1), [UO2Ni(cptpy)2(BTPA)2] (2), [UO2Fe(cptpy)2(HCOO)2(DMF)(H2O)] (3), [UO2Fe(cptpy)2(BTPA)2] (4), [UO2Co(cptpy)2(HCOO)2(DMF)(H2O)] (5), and [UO2Co(cptpy)2(BTPA)2] (6), based on bifunctional ligand 4′‐(4‐carboxyphenyl)‐2,2′:6′,2′′‐terpyridine (Hcptpy) are reported (H2BTPA = 4,4′‐biphenyldicarboxylic acid). Single‐crystal XRD revealed that all six compounds feature similar metalloligands, which consist of two cptpy−anions and one transition metal cation. The metalloligand M(cptpy)2can be considered to be an extended linear dicarboxylic ligand with length of 22.12 Å. Compounds 1,3, and5are isomers, and all of them feature 1D chain structures. The adjacent 1D chains are connected together by hydrogen bonds and π–π interactions to form a 3D porous structure, which is filled with solvent molecules and can be exchanged with I2. Compounds 2,4, and6are also isomers, and all of them feature 2D honeycomb (6,3) networks with hexagonal units of dimensions 41.91×26.89 Å, which are the largest among uranyl compounds with honeycomb networks. The large aperture allows two sets of equivalent networks to be entangled together to result in a 2D+2D→3D polycatenated framework. Remarkably, these uranyl compounds exhibit high catalytic activity for cycloaddition of carbon dioxide. Moreover, the geometric and electronic structures of compounds 1and2are systematically discussed on the basis of DFT calculations.
Polyvalent Transition‐State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases**
Authors: Assailly Coralie , Bridot Clarisse , Saumonneau Amélie , Lottin Paul , Roubinet Benoit , Krammer Eva‐Maria , François Francesca , Vena Federica , Landemarre Ludovic , Alvarez Dorta Dimitri , Deniaud David , Grandjean Cyrille , Tellier Charles , Pascual Sagrario , Montembault Véronique , Fontaine Laurent , Daligault Franck , Bouckaert Julie , Gouin Sébastien G.
Published: November 2020

Bacterial sialidases (SA) are validated drug targets expressed by common human pathogens such as Streptococcus pneumoniae, Vibrio cholerae, or Clostridium perfringens. Noncovalent inhibitors of bacterial SA capable of reaching the submicromolar level are rarely reported. In this work, multi‐ and polyvalent compounds are developed, based on the transition‐state analogue 2‐deoxy‐2,3‐didehydro‐N‐acetylneuraminic (DANA). Poly‐DANA inhibits the catalytic activity of SA from S. pneumoniae (NanA) and the symbiotic microorganism B. thetaiotaomicron (BtSA) at the picomolar and low nanomolar levels (expressed in moles of molecules and of DANA, respectively). Each DANA grafted to the polymer surpasses the inhibitory potential of the monovalent analogue by more than four orders of magnitude, which represents the highest multivalent effect reported so far for an enzyme inhibition. The synergistic interaction is shown to operate exclusively in the catalytic domain, and not in the flanked carbohydrate‐binding module (CBM). These results offer interesting perspectives for the multivalent inhibition of other SA families lacking a CBM, such as viral, parasitic, or human SA.
Solubility‐Controlled Room‐Temperature Synthesis of Cesium Lead Halide Perovskite Nanocrystals
Authors: Kirakosyan Artavazd , Kim Yeonho , Sihn Moon Ryul , Jeon Min‐Gi , Jeong Jong‐Ryul , Choi Jihoon
Published: November 2020

All‐inorganic lead halide perovskite (IHP) nanocrystals (NC) have demonstrated to be a promising active material in a wide range of optoelectronic applications due to their chemical and thermal stability compared to organic‐inorganic perovskite NCs. However, the synthetic procedure of IHP NC generally requires a high‐temperature reaction of the precursors due to their limited solubility. Alternatively, the affinity of the precursor elements to the solvent was controlled to enhance their solubility in the liquid phase, and thus the enhanced kinetics in the crystallization process. Here, we show how the controlled solubility of Cs salts (i. e., Cs halide, acetate, carbonate) influences on their crystallization process and their optical properties. The formation of highly luminescent CsPbX3 (X=Cl, Br, and mixed Br/Cl and Br/I) NCs with a well‐controlled crystallinity and morphology provide fundamental insights into their crystallization process, broadening their applications in the optoelectronic devices.
Cancer Cell Membrane Technology for Cancer Therapy
Authors: Rao Chethana , Mishra Pushpendra Mani , Yadav Aditya , Nandi Chayan Kanti
Published: November 2020

Even after decades of research, one of the most significant challenges in nanotechnology‐based cancer therapy is to increase the target specificity and to reduce the side effects. As a result, even after substantial progress in lab‐scale research, clinical trials have mostly failed. One of the emerging new strategies to increase the target specificity and to increase the chemotherapeutic efficacy is to mimic biological moieties using cellular membranes. Owing to its preferential accumulation at the tumor site, cancer cell membrane presents itself as a promising surface functionalization to the nanocarriers. This review aims to summarize recent reports on the cancer cell membrane and the hybrid membrane‐associated research for the comprehensive understanding of their successful implementation in cancer therapy.
Base Editing in Human Cells to Produce Single‐Nucleotide‐Variant Clonal Cell Lines
Authors: Vasquez Carlos A. , Cowan Quinn T. , Komor Alexis C.
Published: November 2020

Base‐editing technologies enable the introduction of point mutations at targeted genomic sites in mammalian cells, with higher efficiency and precision than traditional genome‐editing methods that use DNA double‐strand breaks, such as zinc finger nucleases (ZFNs), transcription‐activator‐like effector nucleases (TALENs), and the clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR‐associated protein 9 (CRISPR‐Cas9) system. This allows the generation of single‐nucleotide‐variant isogenic cell lines (i.e., cell lines whose genomic sequences differ from each other only at a single, edited nucleotide) in a more time‐ and resource‐effective manner. These single‐nucleotide‐variant clonal cell lines represent a powerful tool with which to assess the functional role of genetic variants in a native cellular context. Base editing can therefore facilitate genotype‐to‐phenotype studies in a controlled laboratory setting, with applications in both basic research and clinical applications. Here, we provide optimized protocols (including experimental design, methods, and analyses) to design base‐editing constructs, transfect adherent cells, quantify base‐editing efficiencies in bulk, and generate single‐nucleotide‐variant clonal cell lines. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Design and production of plasmids for base‐editing experiments

Basic Protocol 2: Transfection of adherent cells and harvesting of genomic DNA

Basic Protocol 3: Genotyping of harvested cells using Sanger sequencing

Alternate Protocol 1: Next‐generation sequencing to quantify base editing

Basic Protocol 4: Single‐cell isolation of base‐edited cells using FACS

Alternate Protocol 2: Single‐cell isolation of base‐edited cells using dilution plating

Basic Protocol 5: Clonal expansion to generate isogenic cell lines and genotyping of clones
Model‐Informed Drug Development for Antimicrobials: Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin
Authors: Sou Tomás , Hansen Jon , Liepinsh Edgars , Backlund Maria , Ercan Onur , Grinberga Solveiga , Cao Sha , Giachou Paraskevi , Petersson Anna , Tomczak Magdalena , Urbas Malgorzata , Zabicka Dorota , Vingsbo Lundberg Carina , Hughes Diarmaid , Hobbie Sven N. , Friberg Lena E.
Published: November 2020

Apramycin represents a subclass of aminoglycoside antibiotics that has been shown to evade almost all mechanisms of clinically relevant aminoglycoside resistance. Model‐informed drug development may facilitate its transition from preclinical to clinical phase. This study explored the potential of pharmacokinetic/pharmacodynamic (PK/PD) modeling to maximize the use of in vitro time‐kill and in vivo preclinical data for prediction of a human efficacious dose (HED) for apramycin. PK model parameters of apramycin from four different species (mouse, rat, guinea pig, and dog) were allometrically scaled to humans. A semimechanistic PK/PD model was developed from the rich in vitro data on four Escherichia coli strains and subsequently the sparse in vivo efficacy data on the same strains were integrated. An efficacious human dose was predicted from the PK/PD model and compared with the classical PK/PD index methodology and the aminoglycoside dose similarity. One‐compartment models described the PK data and human values for clearance and volume of distribution were predicted to 7.07 L/hour and 26.8 L, respectively. The required fAUC/MIC (area under the unbound drug concentration‐time curve over MIC ratio) targets for stasis and 1‐log kill in the thigh model were 34.5 and 76.2, respectively. The developed PK/PD model predicted the efficacy data well with strain‐specific differences in susceptibility, maximum bacterial load, and resistance development. All three dose prediction approaches supported an apramycin daily dose of 30 mg/kg for a typical adult patient. The results indicate that the mechanistic PK/PD modeling approach can be suitable for HED prediction and serves to efficiently integrate all available efficacy data with potential to improve predictive capacity.
Urochloa spp. multivariate performance: Similarities and divergences among intra‐ and interspecific populations
Authors: Matias Filipe Inácio , Candido Anderson Ramires , Machado Wyverson Kim Rocha , Cesar do Amaral Pedro Nelson , Dias Alexandre Menezes , Borges do Valle Cacilda , Barrios Sanzio Carvalho Lima , Valerio José Raul , Torres Fabricia Zimermann Vilela , Verzignassi Jaqueline Rosemeire , de Arruda Cassia Oliveira Camargo Barros , Gouveia Beatriz Tomé , Nobre Alana Aparecida Amarilha
Published: November 2020

Multivariate analysis is a tool that breeders can use to compare populations and select genotypes for specific purposes. This study used principal component analysis to compare three intraspecific and three interspecific populations of Urochloa spp. based on insect resistance, agronomic, and seed production characteristics. This multivariate strategy exposed completely different profiles and important differences among these populations despite their close genomic ancestry. In general, interspecific populations had greater variability than intraspecific populations for agronomic traits, seed production, and spittlebug resistance. Consequently, crosses among different species, whenever possible, are a better option to obtain new Urochloa breeding populations. However, the breeding of intraspecific populations is also an excellent option to improve specific traits related to each species, which can then be used to speed the breeding in the interspecific programs. Multivariate analysis demonstrated substantial variability within progenies of the interspecific Urochloa populations that can be used to improve insect resistance and productivity of tropical pastures.
Hydrogen Production by Steam Electrolysis in Solid Acid Electrolysis Cells
Authors: Fujiwara Naoya , Nagase Hironori , Tada Shohei , Kikuchi Ryuji
Published: November 2020

Hydrogen production by steam electrolysis at intermediate temperatures has potential for both the high energy conversion efficiency and the flexible operability suitable for the utilization of renewable energy resources. Employment of proton‐conducting solid acid electrolytes at around 200 °C is considered promising but has rarely been investigated. Here, steam electrolysis was performed at 160–220 °C using a solid acid electrolysis cell (SAEC) composed of a CsH2PO4/SiP2O7 composite electrolyte and Pt/C electrodes. Hydrogen production was successfully demonstrated with Faraday efficiencies around 80 %. Key factors affecting the SAEC stability were investigated in detail for the first time. It was revealed that a certain part of the electrolyte migrated into the porous anode structure during the operation. The migrated electrolyte prevented the gas diffusion and flooded the Pt/C catalyst layer. It was also found that carbonaceous materials in the anode was oxidized, leading to the decrease in the number of electrochemically active sites. Based on the findings, Pt mesh was employed as an alternative anode. The SAEC with the Pt mesh anode showed superior stability, demonstrating the importance of the anode design. The present work provides a comprehensive view of the stability issues, which is essential for the development of durable and practical SAECs.
Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy‐induced cytokine release syndrome
Authors: Matas‐Céspedes Alba , Brown Lee , Mahbubani Krishnaa T , Bareham Bethany , Higgins Jackie , Curran Michelle , de Haan Lolke , Lapointe Jean‐Martin , Stebbings Richard , Saeb‐Parsy Kourosh
Published: November 2020

Objectives

Humanised mice have emerged as valuable models for pre‐clinical testing of the safety and efficacy of immunotherapies. Given the variety of models available, selection of the most appropriate humanised mouse model is critical in study design. Here, we aimed to develop a model for predicting cytokine release syndrome (CRS) while minimising graft‐versus‐host disease (GvHD).

Methods

To overcome donor‐induced variation, we directly compared the in vitro and in vivo immune phenotype of immunodeficient NSG mice reconstituted with human bone marrow (BM) CD34+ haematopoietic stem cells (HSCs), peripheral blood mononuclear cells (PBMCs) or spleen mononuclear cells (SPMCs) from the same human donors. SPMC engraftment in NSG‐dKO mice, which lack MHC class I and II, was also evaluated as a strategy to limit GvHD. Another group of mice was engrafted with umbilical cord blood (UCB) CD34+ HSCs. Induction of CRS in vivo was investigated upon administration of the anti‐CD3 monoclonal antibody OKT3.

Results

PBMC‐ and SPMC‐reconstituted NSG mice showed short‐term survival, with engrafted human T cells exhibiting mostly an effector memory phenotype. Survival in SPMC‐reconstituted NSG‐dKO mice was significantly longer. Conversely, both BM and UCB‐HSC models showed longer survival, without demonstrable GvHD and a more naïve T‐cell phenotype. PBMC‐ and SPMC‐reconstituted mice, but not BM‐HSC or UCB‐HSC mice, experienced severe clinical signs of CRS upon administration of OKT3.

Conclusion

PBMC‐ and SPMC‐reconstituted NSG mice better predict OKT3‐mediated CRS. The SPMC model allows generation of large experimental groups, and the use of NSG‐dKO mice mitigates the limitation of early GvHD.
A paradoxical phenomenon: Intense pulsed light‐induced hypertrichosis, a brief review
Authors: Baah Natasha , Chacon Anna H.
Published: November 2020

The advancement of laser and light therapies have allowed patients of all races and ethnicities access to different methods for removing unwanted hairs that can cause emotional distress and impact one's quality of life. Despite their effectiveness, these technologies are not without their risks, such as the well‐known side effects of blister formation, erythema, crusting, and postinflammatory hypo‐ and hyperpigmentation. However, one adverse effect that seems to remain a clinical mystery is paradoxical hypertrichosis. Paradoxical hypertrichosis is the growth of fine, dark hair in treated areas or untreated areas close to the area treated on the face and neck, more frequently affecting those with darker skin (Fitzpatrick III‐VI) and darker hair color, and most associated with those having undergone the intense pulsed laser and long‐pulse alexandrite laser, although, this adverse reaction is likely common to all current and laser and light hair removal devices, despite the unknown prevalence and varying incidence rates. This phenomenon is not well understood, although explanations include the activation of dormant hair follicles by the intense pulse light flashlamp's suboptimal fluences and the synchronization of hair growth cycles caused by direct light stimulation.
Two‐dimensional high performance liquid chromatography purification of underivatized urinary testosterone and metabolites for compound‐specific stable carbon isotope analysis
Authors: Lalonde Karine , Barber Andrew , Ayotte Christiane
Published: November 2020

Testosterone doping in sports is detected through the measurement of the carbon isotopic signature (δ13C) of testosterone and its metabolites in urine. A critical step in achieving accurate and precise δ13C values during compound‐specific stable carbon isotope analysis (CSIA) is the removal of interfering matrix components. To this end, the World Anti‐Doping Agency (WADA) recommends the use of high‐performance liquid chromatography (HPLC) as a method of sample pretreatment. We provide a description of an automated two‐dimensional HPLC (2D‐HPLC) purification method for urine extracts that has made possible the CSIA of underivatized steroids, requiring only 36 min per sample. Eight urinary steroids including testosterone (T) and dehydroepiandrosterone (DHEA) and four of their metabolites as well as two endogenous reference compounds were collected during HPLC purification. Comparative GC chromatograms are used to contrast the efficiency of two‐dimensional (2D) purification to a previously established 1D‐HPLC method. The 2D purification leads to improved sample purity while simultaneously decreasing the analysis time, allowing for unprecedented sample throughput. Precision of δ13C for all analyzed compounds in negative and positive controls was 0.5‰ or better, which is comparable with the precision of pure reference materials at similar intensities.
Morphometric and genetic evidence for four species of gentoo penguin
Authors: Tyler Joshua , Bonfitto Matthew T. , Clucas Gemma V. , Reddy Sushma , Younger Jane L.
Published: November 2020

Gentoo penguins (Pygoscelis papua) are found across the Southern Ocean with a circumpolar distribution and notable genetic and morphological variation across their geographic range. Whether this geographic variation represents species‐level diversity has yet to be investigated in an integrative taxonomic framework. Here, we show that four distinct populations of gentoo penguins (Iles Kerguelen, Falkland Islands, South Georgia, and South Shetlands/Western Antarctic Peninsula) are genetically and morphologically distinct from one another. We present here a revised taxonomic treatment including formal nomenclatural changes. We suggest the designation of four species of gentoo penguin: P. papua in the Falkland Islands, P. ellsworthi in the South Shetland Islands/Western Antarctic Peninsula, P. taeniata in Iles Kerguelen, and a new gentoo species P. poncetii, described herein, in South Georgia. These findings of cryptic diversity add to many other such findings across the avian tree of life in recent years. Our results further highlight the importance of reassessing species boundaries as methodological advances are made, particularly for taxa of conservation concern. We recommend reassessment by the IUCN of each species, particularly P. taeniata and P. poncetii, which both show evidence of decline.
Microwave‐assisted hydrothermal synthesis of Cu‐doped TiO2 nanoparticles for efficient dye‐sensitized solar cell with improved open‐circuit voltage
Authors: Sahu Kirti , Dhonde Mahesh , Murty Vemparala Venkata Satyanarayana
Published: November 2020

An important reason for the underlying power conversion efficiency (PCE) of the dye sensitized solar cells (DSSCs) is the low open‐circuit voltage (Voc). Considerable efforts have been made to increase the Voc of DSSCs by suppressing charge carrier recombination dynamics, co‐sensitization, and other strategies. Herein, we report an enhancement of the Voc by the incorporation of Cu into TiO2 microstructure via microwave‐assisted hydrothermal synthesis. The prepared nanoparticles and the photoanodes were tested for their efficacy with various structural, optical, and electrical characterization tools. It was found that the incorporation of Cu2+ into TiO2 lattice raises its conduction band (CB) edge and shifted the Fermi level upwards, which contribute towards enhanced Voc. A significant enhancement in Voc from 0.714 to 0.781 V was observed by the Cu incorporation. An optimized 1 wt% Cu modified TiO2 DSSC has shown an efficiency of 6.94% with a high Voc of 0.762 V.
Peritoneal HPV‐DNA test in cervical cancer (PIONEER study): A proof of concept
Authors: Bizzarri Nicolò , Pedone Anchora Luigi , Cattani Paola , De Vincenzo Rosa , Marchetti Simona , Conte Carmine , Chiantera Vito , Gallotta Valerio , Gueli Alletti Salvatore , Vizzielli Giuseppe , Costantini Barbara , Fagotti Anna , Fanfani Francesco , Scambia Giovanni , Ferrandina Gabriella
Published: November 2020

The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single‐center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV‐DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two‐hundred seventy‐two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P = .001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (P = .003), presence of cervical HPV 16/18 genotypes (P < .001), higher number of cervical high‐risk (HR)‐HPV per patient (P = .018) and peritoneal carcinomatosis (P < .001). Multivariate analysis demonstrated that lack of preoperative cervical conization in early stages (P = .030), while higher International Federation of Gynecology and Obstetrics (FIGO) stage (P = .021) and presence of cervical HPV 16/18 (P = .001) in LACC, was associated with PHP. This is a proof‐of‐concept study. A number of potential clinical implications, including prognosis, could be obtained by further studies.
Targeting stromal cell Syndecan‐2 reduces breast tumour growth, metastasis and limits immune evasion
Authors: Loftus Paul G. , Watson Luke , Deedigan Laura M. , Camarillo‐Retamosa Eva , Dwyer Róisín M. , O'Flynn Lisa , Alagesan Senthilkumar , Griffin Matthew , O'Brien Timothy , Kerin Michael J. , Elliman Stephen J. , Barkley Laura R.
Published: November 2020

Tumour stromal cells support tumourigenesis. We report that Syndecan‐2 (SDC2) is expressed on a nonepithelial, nonhaematopoietic, nonendothelial stromal cell population within breast cancer tissue. In vitro,syndecan‐2 modulated TGFβ signalling (SMAD7, PAI‐1), migration and immunosuppression of patient‐derived tumour‐associated stromal cells (TASCs). In an orthotopic immunocompromised breast cancer model, overexpression of syndecan‐2 in TASCs significantly enhanced TGFβ signalling (SMAD7, PAI‐1), tumour growth and metastasis, whereas reducing levels ofSDC2in TASCs attenuated TGFβ signalling (SMAD7, PAI‐1, CXCR4), tumour growth and metastasis. To explore the potential for therapeutic application, a syndecan‐2‐peptide was generated that inhibited the migratory and immunosuppressive properties of TASCs in association with reduced expression of TGFβ‐regulated immunosuppressive genes, such asCXCR4and PD‐L1. Moreover, using an orthotopic syngeneic breast cancer model, overexpression of syndecan‐2‐peptide in TASCs reduced tumour growth and immunosuppression within the TME. These data provide evidence that targeting stromal syndecan‐2 within the TME inhibits tumour growth and metastasis due to decreased TGFβ signalling and increased immune control.
Paying the price for anger: Do women bear greater costs?
Authors: Van Doren Natalia , Soto José A.
Published: November 2020

Prior research shows that the social costs of expressing anger may be greater for women than for men. However, less is known about whether anger expression is also associated with greater intrapersonal costs for women relative to men. We tested the hypothesis that outward anger expression would be related to greater depressive symptoms over time for women, but not men. A nationally representative sample of 942 community‐dwelling adults reported on their frequency of anger expression and completed diagnostic interviews to assess depressive symptoms at baseline and 9‐year follow‐up. Moderation analyses using bootstrapping revealed a significant main effect of anger‐out on depression. As predicted, gender moderated the effects of anger‐out on depression, such that greater anger‐out at baseline predicted greater depression in women 9 years later, even after controlling for baseline depression. Findings add to the literature by revealing the intrapersonal costs women may incur from anger expression.