bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Cellular Labeling of Multifunctional Phosphatidylinositol Bis‐ and Trisphosphate Derivatives
Authors: Müller Rainer , Kojic Ana , Citir Mevlut , Schultz Carsten
Published: June 2021

We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo‐removable protecting group (“cage”), a photo‐crosslinkable diazirine group, and a terminal alkyne group useful for click chemistry. We demonstrate that the lipid derivatives readily enter cells. After photo‐crosslinking, cell fixation and fluorescent tagging via click chemistry, we determined the intracellular location of the lipid derivatives before and after uncaging of the lipids. We find that there is rapid trafficking of PI(3,4)P2 and PI(3,4,5)P3 derivatives to the plasma membrane, opening the intriguing possibility that there is active transport of these lipids involved. We employed the photo‐crosslinking and click chemistry functions to analyze the proteome of PI(3,4,5)P3‐binding proteins. From the latter, we validated by RNAi that the putative lipid binding proteins ATP11A and MPP6 are involved in the transport of PI(3,4,5)P3 to the plasma membrane.
Materials Engineering of Violin Soundboards by Stradivari and Guarneri
Authors: Su Cheng‐Kuan , Chen Szu‐Yu , Chung Jen‐Hsuan , Li Guo‐Chian , Brandmair Brigitte , Huthwelker Thomas , Fulton John L. , Borca Camelia N. , Huang Shing‐Jong , Nagyvary Joseph , Tseng Hsiao‐Han , Chang Chih‐Hui , Chung Dai‐Ting , Vescovi Rafael , Tsai Yi‐Shiuan , Cai Wenjie , Lu Bing‐Jyun , Xu Jia‐Wei , Hsu Chia‐Shuo , Wu Jun‐Jie , Li Hao‐Zhi , Jheng Yu‐Kai , Lo Sheng‐Fong , Chen Hao Ming , Hsieh Yi‐Ting , Chung Po‐Wen , Chen Chien‐Sheng , Sun Yuh‐Chang , Chan Jerry Chun Chung , Tai Hwan‐Ching
Published: June 2021

We investigated the material properties of Cremonese soundboards using a wide range of spectroscopic, microscopic, and chemical techniques. We found similar types of spruce in Cremonese soundboards as in modern instruments, but Cremonese spruces exhibit unnatural elemental compositions and oxidation patterns that suggest artificial manipulation. Combining analytical data and historical information, we may deduce the minerals being added and their potential functions—borax and metal sulfates for fungal suppression, table salt for moisture control, alum for molecular crosslinking, and potash or quicklime for alkaline treatment. The overall purpose may have been wood preservation or acoustic tuning. Hemicellulose fragmentation and altered cellulose nanostructures are observed in heavily treated Stradivari specimens, which show diminished second‐harmonic generation signals. Guarneri's practice of crosslinking wood fibers via aluminum coordination may also affect mechanical and acoustic properties. Our data suggest that old masters undertook materials engineering experiments to produce soundboards with unique properties.
Redox‐Mediated Ambient Electrolytic Nitrogen Reduction for Hydrazine and Ammonia Generation
Authors: Wang Xun , Yang Jing , Salla Manohar , Xi Shibo , Yang Yi , Li Mengsha , Zhang Feifei , Zhu Ming‐Ke , Huang Songpeng , Huang Shiqiang , Zhang Yong‐Wei , Wang Qing
Published: June 2021

This work presents a redox‐mediated electrolytic nitrogen reduction reaction (RM‐eNRR) using polyoxometalate (POM) as the electron and proton carrier which frees the TiO2‐based catalyst from the electrode and shifts the reduction of nitrogen to a reactor tank. The RM‐eNRR process has achieved an ammonium production yield of 25.1 μg h−1 or 5.0 μg h−1 cm−2 at an ammonium concentration of 6.7 ppm. With high catalyst loading, 61.0 ppm ammonium was accumulated in the electrolyte upon continuous operation, which is the highest concentration detected for ambient eNRR so far. The mechanism underlying the RM‐eNRR was scrutinized both experimentally and computationally to delineate the POM‐mediated charge transfer and hydrogenation process of nitrogen molecule on the catalyst. RM‐eNRR is expected to provide an implementable solution to overcome the limitations in the conventional eNRR process.
The acetylation modification regulates the stability of Bm30K‐15 protein and its mechanism in silkworm, Bombyx mori
Authors: Lv Jiao , Li Shouliang , Liu Yue , Sun Zihan , Wang Dan , You Zhengying , Jiang Caiying , Sheng Qing , Nie Zuoming
Published: June 2021

The 30 K proteins are the major silkworm hemolymph proteins and are involved in a variety of physiological processes, such as nutrient and energy storage, embryogenesis, immune response, and inhibition of apoptosis. The Bm30K‐15 protein is one of the 30 K proteins and is abundant in the hemolymph of fifth instar silkworm larva. We previously found that the Bm30K‐15 protein can be acetylated. In the present study, we found that acetylation can improve the protein stability of Bm30K‐15. Further exploration confirmed that the increase in protein stability by acetylation was caused by competition between acetylation and ubiquitination. In summary, these findings aim to provide insight into the effect of acetylation modification on the protein level and stability of the Bm30K‐15 and the possible molecular mechanism of its existence in silkworm, Bombyx mori.
Purification of a novel protein with cytotoxicity against non‐small‐cell lung cancer cells from Boletus bicolor
Authors: Zhang Min‐Hui , Zhou Rong , Liu Fang , Ng Tzi B.
Published: June 2021

A novel protein (D1 component) was purified from Boletus bicolor by ion‐exchange chromatography and gel chromatography on a HiTrap™ Q HP column, a diethylaminoethanol cellulose‐52 column, and a Sephadex G75 column, respectively. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed that the D1 component was a single protein band with a molecular weight of about 40 kDa. The sulforhodamine B assay showed that at concentrations as low as 25–75 μg/ml, protein D1 significantly inhibited the proliferation of human lung adenocarcinoma cell lines (A549 and H1299 cells) and had little effect on human normal kidney cells (HEK293 cells). After labeling protein D1, it was found that D1 could enter the cytoplasm of tumor cells and colocated with lysosomes. Flow cytometry results demonstrated that protein D1 induced apoptosis and G1 phase arrest of the cell cycle in A549 and H1299 cells. The Western blot analysis results showed that the expression of apoptosis and cell cycle‐related proteins of cleaved caspase‐3, cytochrome c, Bax, P16, and P21 was significantly upregulated, whereas the expression of Bcl‐2, CDK4, cyclin D, p‐Rb, and E2F was significantly downregulated after treatment with protein D1. Therefore, D1 exhibits potential to be developed into an antitumor agent.
The association of adverse life events and parental mental health with emotional and behavioral outcomes in young adults with autism spectrum disorder
Authors: Hollocks Matthew J. , Meiser‐Stedman Richard , Kent Rachel , Lukito Steve , Briskman Jackie , Stringer Dominic , Lord Catherine , Pickles Andrew , Baird Gillian , Charman Tony , Simonoff Emily
Published: June 2021

People with autism spectrum disorder (ASD) are at increased risk of developing co‐occurring mental health difficulties across the lifespan. Exposure to adverse life events and parental mental health difficulties are known risk factors for developing a range of mental health difficulties. This study investigates the association of adverse life events, parental stress and mental health with emotional and behavioral problems in young adults with ASD. One hundred and fifteen young adults with ASD derived from a population‐based longitudinal study were assessed at three time‐points (12‐, 16‐, and 23‐year) on questionnaire measures of emotional and behavioral problems. Parent‐reported exposure to adverse life events and parental stress/mental health were measured at age 23. We used structural equation modeling to investigate the stability of emotional and behavioral problems over time, and the association between adverse life events and parental stress and mental health and emotional and behavioral outcomes at 23‐year. Our results indicate that exposure to adverse life events was significantly associated with increased emotional and behavioral problems in young adults with ASD, while controlling for symptoms in childhood and adolescence. Higher reported parental stress and mental health difficulties were associated with a higher frequency of behavioral, but not emotional problems, and did not mediate the impact of adverse life events. These results suggest that child and adolescent emotional and behavioral problems, exposure to life events and parent stress and mental health are independently associated, to differing degrees, with emotional or behavioral outcomes in early adulthood.

Lay Summary

People with autism experience high rates of mental health difficulties throughout childhood and into adult life. Adverse life events and parental stress and mental health may contribute to poor mental health in adulthood. We used data at three time points (12‐, 16‐, and 23‐year) to understand how these factors relate to symptoms at 23‐year. We found that emotional and behavioral problems in childhood, adverse life events and parent mental health were all associated with increased emotional and behavioral problems in adulthood.
Marginalized Counselor Educators' Experiences Negotiating Identity: A Narrative Inquiry
Authors: Thacker Nancy E. , Minton Casey A. Barrio , Riley Kertesha B.
Published: June 2021

Counseling professionals who identify as people of color, women, and gender or sexual minorities commonly suppress or negotiate their personal identities due to experiencing adversity. We describe findings from a narrative inquiry of counselor educators' experiences negotiating marginalized identities. Implications for intersectional praxis—including reflexivity, mentorship, and power deconstruction—are discussed.
The Deuterated “Magic Methyl” Group: A Guide to Site‐Selective Trideuteromethyl Incorporation and Labeling by Using CD3Reagents
Authors: Steverlynck Joost , Sitdikov Ruzal , Rueping Magnus
Published: June 2021

In the field of medicinal chemistry, the precise installation of a trideuteromethyl group is gaining ever‐increasing attention. Site‐selective incorporation of the deuterated “magic methyl” group can provide profound pharmacological benefits and can be considered an important tool for drug optimization and development. This review provides a structured overview, according to trideuteromethylation reagent, of currently established methods for site‐selective trideuteromethylation of carbon atoms. In addition to CD3, the selective introduction of CD2H and CDH2groups is also considered. For all methods, the corresponding mechanism and scope are discussed whenever reported. As such, this review can be a starting point for synthetic chemists to further advance trideuteromethylation methodologies. At the same time, this review aims to be a guide for medicinal chemists, offering them the available C−CD3formation strategies for the preparation of new or modified drugs.
Establishing a “Ring‐Size‐Divergent” Synthetic Strategy: Synthesis, Structural Revision, and Absolute Configuration of Feroniellins
Authors: Nishikawa Keisuke , Niwa Toshiki , Nishikibe Kento , Kumagai Momochika , Morimoto Yoshiki
Published: June 2021

Feroniellin analogs isolated from Feroniella lucida possess a furanocoumarin skeleton connected to monoterpenic five‐ to seven‐membered ethereal rings by an ether linkage and exhibit a broad spectrum of biological activities. In this contribution, we intended to establish a “ring‐size‐divergent” synthetic strategy for the monoterpenic five‐ to seven‐membered ethereal rings through the chemical sythesis of feroniellins. The short and comprehensive synthesis of feroniellins was achieved in only two steps from easily available bergamottin based on the “ring‐size‐divergent” strategy. In addition, these syntheses resulted in revision of the proposed structures for feroniellins A and B and the determination of all the absolute configurations of feroniellins; their preliminary anti‐inflammatory activities were investigated as well.
Pathologic T1 and T2 encapsulated invasive carcinomas arising from mucinous cystic neoplasms of the pancreas have favorable prognosis and might be treated conservatively
Authors: Liang Huaiyu , Xie Wen , Lin Xiaozhu , Wang Ting , Xie Jing , Wang Chaofu , Xiao Shu‐Yuan , Guo Yan
Published: June 2021

Carcinoma arising from a mucinous cystic neoplasm (MCN) of the pancreas is termed MCN with associated invasive carcinoma (MCN‐AIC) in the fifth WHO classification of digestive tumors (2019). The prognosis of this malignancy varies depending on the relationship of the invasive carcinoma to the cyst capsule, but limited data are available. This study identified 165 surgically resected MCNs including 15 MCN‐AICs from a single center between 2008 and 2018 and analyzed their clinicopathologic features. The results confirmed that non‐invasive MCNs were completely cured by surgery. All MCN‐AICs showing an encapsulated invasion pattern (defined as invasive carcinoma limited to the ovarian‐type stroma, cystic septa, and capsule) had an excellent prognosis with a 5‐year survival rate of 100%, even when the size of the invasive component was up to stage T2. By contrast, MCN‐AICs with extracapsular involvement had unfavorable clinical outcomes. Our study demonstrates that the pattern of invasion of MCN‐AIC can predict patient prognosis. Pathologic stage T1 and T2 encapsulated MCN‐AICs may be completely cured with surgical resection alone or when combined with postoperative chemotherapy.
Solid state drive forensics analysis—Challenges and recommendations
Authors: Kumar Manish
Published: June 2021

Solid state drive (SSD) is rapidly replacing hard disk drive (HDD) in almost all computing devices. With the exponential growth in SSD technologies, it is quite possible that very soon HDD will become obsolete. It is good news for the end‐users, but may not be so pleasant for the digital forensics examiners. It has been a challenge for the cyber‐crime investigator ever since the evolution of SSD technology. The intrinsic characteristics of SSD are not very supportive for forensic examiners. The TRIM function and background garbage process make it difficult to retrieve deleted artifacts from the SSD. The traditional disk write blocker cannot stop the background process. There is a lot of uncertainty involved in SSD data acquisition. Sometimes it is also difficult to prove the integrity of SSD in the court of law which makes the SSD's legal admissibility questionable. The objective of this article is to examine the uncertainty involved in SSD forensics with experimental analysis. This article discusses in detail the different components of SSD and its working principle followed by experimental forensics analysis, critical observations, guidelines, and recommendations.
Premature degeneration of tapetum cells causes monogenically controlled environmentally stable male sterility in psyllium
Authors: Kavane Aarti , Bishoyi Ashok Kumar , Sharma Anjali , Geetha K. A.
Published: June 2021

Psyllium (Plantago ovata Forsk.) is an important medicinal species cultivated throughout the semi‐arid areas in India. The seed coat, commercially known as psyllium husk, is used as a laxative for treating irritation of gastro‐intestinal tract and relieving constipation. There is an urgent need to enhance its productivity to make the crop more profitable. Artificial crossing is difficult in the species because of its small‐sized sessile florets that are compactly arranged on a soft inflorescence axis. Male sterility has been reported in the species; however, no conclusive studies have been conducted to reveal the inheritance, mode of action, and cytogenetic basis of male sterility. Hence, the purpose of this study was to determine (a) the histological and cytogenetic bases of anther development and microsporogenesis in male‐sterile and fertile plant types and (b) the genetic basis of male sterility. The study revealed that male sterility in psyllium was not attributable to meiotic abnormality or to tetrad abnormalities, but it was attributable to premature degradation of the tapetum layer, which subsequently causes the microspore degeneration, resulting in nonproduction of pollen grains. Male sterility was controlled by a single recessive gene, which was found to be stable across years and hence can easily be bred into any psyllium genotypes of breeders’ choice. Newly developed male‐sterility‐maintainer line can be used to generate new sets of male‐sterile lines for hybrid seed production or harnessing hybrid vigor in the field.
Interfacial Electronic Coupling of NC@WO3‐W2C Decorated Ru Clusters as a Reversible Catalyst toward Electrocatalytic Hydrogen Oxidation and Evolution Reactions
Authors: Yang Yuting , Shao Xue , Zhou Shuqing , Yan Puxuan , Isimjan Tayirjan Taylor , Yang Xiulin
Published: June 2021

Designing a bifunctional catalyst for hydrogen oxidation reaction (HOR) and hydrogen evolution reaction (HER) is significant toward developing sustainable hydrogen‐electric conversion systems. Herein, a cost‐effective bifunctional catalyst, Ru/N‐doped Carbon@WO3‐W2C (Ru/NC@WOC), was developed via co‐precipitation and polyol reduction. Ru/NC@WOC showed superior HOR/HER activity in alkaline solution in comparison with commercial Pt/C. HOR electrochemical tests showed that the mass activity at 0.05 V (1.96 
) and exchange‐current density were 7.5 and 1.2 times that of Pt/C. Additionality, Ru/NC@WOC exhibited up 30‐fold HOR activity in mass activity compared with benchmark Ru/C. Moreover, it also displayed exceptional electrocatalytic HER with overpotentials of 31 mV at 10 mA cm−2 and 119 mV at 100 mA cm−2, surpassing Pt/C, benchmark Ru/C, and most of the previously reported electrocatalysts. The outstanding catalytic activity of Ru/NC@WOC probably arises from the synergy between Ru and NC@WOC matrix, suitable hydrogen binding energy, and highly conductive substrate. Thus, this work may pave a new avenue to fabricate low‐cost bifunctional HOR/HER catalysts for alkaline fuel cells and water electrolyzer.
3‐Trifloxy‐3‐(trifluoromethyl)prop‐2‐ene 1‐Iminium Salts as Precursors for Elusive 3‐(Trifluoromethyl)prop‐2‐yne 1‐Iminium Salts
Authors: Keim Michael , Konetzke Katharina , Freytag Angelika , Maas Gerhard
Published: June 2021

Abstract: 3‐(Trifluoromethyl)prop‐2‐yne 1‐iminium triflate salts were generated from 3‐trifloxy‐3‐(trifluoromethyl)prop‐2‐ene 1‐iminium salts by triethylamine‐assisted elimination of triflic acid and trapped in situ in various cycloaddition reactions. These included Diels‐Alder reactions with 1,3‐dienes, [2+2] cycloaddition with 1,4‐diphenylbuta‐1,3‐diene, and [3+2] cycloaddition with organoazides. All these reactions revealed the excellent dienophilic and dipolarophilic reactivity of the electrophilic C,C triple bond of the novel 3‐CF3‐propyniminium salts.
Antifungal activity of TiO2/AgBr nanocomposites on some phytopathogenic fungi
Authors: Habibi‐Yangjeh Aziz , Davari Mahdi , Manafi‐Yeldagermani Reza , Alikhah Asl Shervin , Enaiati Samira , Ebadollahi Asgar , Feizpoor Solmaz
Published: June 2021

TiO2/AgBr composites were synthesized by a simple ultrasonic strategy. Various instruments such as SEM, EDX, XRD, and FT‐IR were exploited to investigate their characteristics. Antifungal activities of the as‐obtained samples were assessed through the inactivation of Fusarium graminearum in the spore suspension method and mycelial growth inhibition of F. graminearum, Botrytis cinerea, and Sclerotinia sclerotiorum in the microdilution method. The results represented that the TiO2/AgBr samples possess higher antifungal activities on F. graminearum spores than the pure TiO2. The sample with 20 wt% silver bromide represented the highest inhibitory effect on the growth of F. graminearum so that all fungal spores were degraded in the initial times of the treatment process. The inactivation of fungal spores after 60 min was 35.2%, 97.8%, 98.9%, and 98.7%, in respect, for 5, 10, 20, and 30 weight percent of AgBr in the binary nanocomposites, while the inhibition rate was 13.4% for the pure TiO2. With increasing ultrasound irradiation time for more than 30 min, the inactivation rate constant decreased. It was also found that the antifungal activity of the nanocomposites without calcination was higher than those of the calcined materials. Considering the antifungal potential against phytopathogenic fungi and advantages such as simple synthesis and eco‐friendly nature, it seems that TiO2/AgBr nanocomposites can be used instead of synthetic chemicals after additional field investigations and mass production.
Clinical analysis of patients with primary and secondary extranodal natural killer/T‐cell lymphoma of central nervous system
Authors: Li Xingying , Yu Hui , Fu Xiaorui , Zhang Lei , Li Xin , Li Ling , Wang Xinhua , Sun Zhenchang , Zhang Xudong , Li Zhaoming , Wu Jingjing , Chang Yu , Yan Jiaqin , Zhou Zhiyuan , Nan Feifei , Wu Xiaolong , Tian Li , Zhang Mingzhi
Published: June 2021

Extranodal natural killer (NK)/T‐cell lymphoma (NKTL) is a rare non‐Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5‐year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T‐cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.
Protective effect of dimethyl itaconate against fibroblast–myofibroblast differentiation during pulmonary fibrosis by inhibiting TXNIP
Authors: Han Yong‐Yue , Gu Xuan , Yang Chong‐Yang , Ji Hui‐Min , Lan Yue‐Jiao , Bi Yu‐Qian , Si Rong , Qu Jiao , Cheng Ming‐Han , Gao Jian
Published: June 2021

Fibroblast–myofibroblast differentiation (FMD) is a critical cellular phenotype during the occurrence and deterioration of pulmonary fibrosis (PF). FMD can increase with an elevated level of reactive oxygen species (ROS) on fibroblasts under oxidative stress. Thioredoxin‐interacting protein (TXNIP) is an α‐arrestin family protein that regulates the level of intracellular ROS. Nuclear factor erythroid 2‐related factor 2 (Nrf2) can protect against FMD in PF. However, the relationship between Nrf2 and TXNIP in FMD remains elusive. Therefore, we established TGF‐β1‐induced FMD in vitro and bleomycin (BLM)‐induced mouse PF model in vivo to explore whether the activation of Nrf2 can inhibit TXNIP‐mediated FMD in PF. Dimethyl itaconate (DMI) was selected to activate Nrf2. Our results showed that TXNIP was elevated and FMD was aggravated in mice lung tissues after BLM administration compared with the saline group. Inversely, Nrf2 decreased TXNIP expression and alleviated FMD in PF. In vitro, TXNIP overexpression enhanced FMD and increased the level of ROS. In contrast, TXNIP deficiency by small interfering RNA (siRNA) attenuated TGF‐β1‐induced FMD and reduced ROS. An increase in ROS by H2O2 can upregulate TXNIP expression. Moreover, Nrf2 also inhibited TGF‐β1‐induced FMD and the increase of ROS, with reducing expression of TXNIP, and the inhibitory effect was better than TXNIP siRNA. These results suggest that activation of Nrf2 by DMI can protect against PF via inhibiting TXNIP expression. Our study may provide new therapeutic targets and treatment approaches for PF.
Chemo‐taxonomic and biological potential of highly therapeutic plantPedicularis groenlandicaRetz. using multiple microscopic techniques
Authors: Hameed Ayesha , Zafar Muhammad , Ahmad Mushtaq , Sultana Shazia , Bahadur Saraj , Anjum Farida , Shuaib Muhammad , Taj Sehrish , Irm Misbah , Altaf Muhammad Ahsan
Published: June 2021

Pedicularis groenlandicais one of the most important medicinal plant of Deosai Plateau (Gilgit‐Baltistan) Pakistan. The present study was aim to evaluate the micromorphological features, phytochemical screening and pharmacological potential ofP. groenlandicaby using multiple microscopic techniques. Six different solvents were used to prepareP. groenlandicaextracts. Phytochemical and antioxidant activities were determined calorimetrically. To investigate antidiabetic, α‐amylase inhibition assay was performed. Cytotoxicity was tested using brine shrimp assay. Anti‐leishmanial via MTT assay. Disc‐diffusion assay was used for protein kinase inhibitory, antibacterial and antifungal activities. Palyno‐anatomical study showed significant variation for the authentication and correct identification of this highly therapeutic plant by using light and scanning electron microscopic techniques. All extracts were found rich in phytochemicals, significant amount of phenolic and flavonoid contents were found in methanol extract (PGM) 95.78 mg GAE/g and 66.90 mg QE/g. Highest DPPH scavenging potential with IC5088.65 μg/mL, total antioxidant capacity (60.33 mg AAE/g sample) and total reducing power (83.97 mg AAE/g) were found for PGM. Disc‐diffusion method showed significant antibacterial and antifungal activities. Noticeable growth inhibition inL. tropicawas displayed by n‐hexane extract (IC50112 μg/mL). Brine shrimp with highest LD50(67.65 μg/mL) in ethyl‐acetate extract. Ethanol extract gives persuasive protein kinase inhibition (26 mm) againstStreptomyces85‐E hyphae. Highest alpha‐amylase inhibition (74.10%) was found in n‐hexane extract. In conclusion, our findings scientifically support the ethno‐medicinal and biological potential ofP. groenlandica. In future, the plant needs to be explored for further identification and isolation of bioactive compounds to develop new drugs to treat several aliments.
Metabolic reprogramming of myeloid-derived suppressor cells: An innovative approach confronting challenges
Authors: Li Xiaoqing , Li Yixue , Yu Qinru , Qian Pengxu , Huang He , Lin Yu
Published: June 2021

Immune cells such as T cells, macrophages, dendritic cells, and other immunoregulatory cells undergo metabolic reprogramming in cancer and inflammation-derived microenvironment to meet specific physiologic and functional demands. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are characterized by immunosuppressive activity, which plays a key role in host immune homeostasis. In this review, we have discussed the core metabolic pathways, including glycolysis, lipid and fatty acid biosynthesis, and amino acid metabolism in the MDSCs under various pathologic situations. Metabolic reprogramming is a determinant of the phenotype and functions of MDSCs, and is therefore a novel therapeutic possibility in various diseases.
The different replication between nonenveloped and quasi‐enveloped hepatitis E virus
Authors: Ji Hanbin , Chen Shuangfeng , He Qiuxia , Wang Wenjing , Gong Shilin , Qian Zhongyao , Zhang Yike , Wei Daqiao , Yu Wenhai , Huang Fen
Published: June 2021

Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. However, the understanding of the HEV life cycle is limited. In the present study, cells were separately infected with nonenveloped HEV (derived from feces or bile) or quasi‐enveloped HEV (derived from the cell culture after serial passages, eHEV) and observed by confocal fluorescence microscopy to investigate the life cycle of HEV. HEV finished its binding and entry into host cells at first 6 h postinoculation (hpi). Cells inoculated with eHEV showed less infectivity than cells inoculated with nonenveloped HEV. Newly synthesized progeny virions were released into the supernatant of cell cultures from 48 hpi. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot analysis results showed that the supernatant's progeny viruses were infectious even after five serial passages. These results show the significant difference between nonenveloped HEV and eHEV, which will provide novel insights into the HEV replication cycle. The efficient cell culture of HEV will promote the development of anti‐HEV drugs and vaccines.
Local relationships matter! The impact of intellectual capital on entrepreneurial bricolage in African social entrepreneurs
Authors: Ciambotti Giacomo , Sgrò Francesca , Bontis Nick , Zaccone Maria Cristina
Published: June 2021

Social entrepreneurs aim to create societal value while pursuing financial sustainability. However, they typically face several challenges and constraints when operating in resource‐scarce environments. For this reason, social entrepreneurs typically engage in entrepreneurial bricolage, which is described as a process of using whatever tools and resources necessary that are immediately available. The behavioral theory of entrepreneurial bricolage attempts to understand what entrepreneurs do when faced with resource constraints. In this vital process, little empirical research has been conducted to investigate what drives social entrepreneurs to engage in such a way. This study aims to understand the antecedents of bricolage and, in particular, empirically test its link to intellectual capital. A survey was administered to 115 social entrepreneurs from Ghana and Sierra Leone. Data analysis shows that relational capital plays a crucial role in driving social entrepreneurs to engage with bricolage. In fact, the quality of local relationships and external support received (by suppliers, customers, and communities) is positively related and statistically significant with entrepreneurial bricolage. The results of this study not only extend the academic literature of bricolage in social entrepreneurship but also point out the focal role of relational capital as an enabler toward effectively operating in difficult conditions in developing African countries. We thus provide theoretical implications to the field of social entrepreneurship through the lens of intellectual capital and knowledge management. Practical implications are provided to social entrepreneurs operating in developing countries, such as government, NGOs, and agencies seeking to support entrepreneurship initiatives. Limitations and future research opportunities are suggested as well.
3D sodium (23Na) magnetic resonance fingerprinting for time‐efficient relaxometric mapping
Authors: Kratzer Fabian J. , Flassbeck Sebastian , Schmitter Sebastian , Wilferth Tobias , Magill Arthur W. , Knowles Benjamin R. , Platt Tanja , Bachert Peter , Ladd Mark E. , Nagel Armin M.
Published: June 2021

Purpose

To develop a framework for 3D sodium (23Na) MR fingerprinting (MRF), based on irreducible spherical tensor operators with tailored flip angle (FA) pattern and time‐efficient data acquisition for simultaneous quantification of T1, , , and in addition to ΔB0.

Methods

23Na‐MRF was implemented in a 3D sequence and irreducible spherical tensor operators were exploited in the simulations. Furthermore, the Cramér Rao lower bound was used to optimize the flip angle pattern. A combination of single and double echo readouts was implemented to increase the readout efficiency. A study was conducted to compare results in a multicompartment phantom acquired with MRF and reference methods. Finally, the relaxation times in the human brain were measured in four healthy volunteers.

Results

Phantom experiments revealed a mean difference of 1.0% between relaxation times acquired with MRF and results determined with the reference methods. Simultaneous quantification of the longitudinal and transverse relaxation times in the human brain was possible within 32 min using 3D 23Na‐MRF with a nominal resolution of (5 mm)3. In vivo measurements in four volunteers yielded average relaxation times of: T1,brain = (35.0 ± 3.2) ms, = (29.3 ± 3.8) ms and = (5.5 ± 1.3) ms in brain tissue, whereas T1,CSF = (61.9 ± 2.8) ms and = (46.3 ± 4.5) ms was found in cerebrospinal fluid.

Conclusion

The feasibility of in vivo 3D relaxometric sodium mapping within roughly ½ h is demonstrated using MRF in the human brain, moving sodium relaxometric mapping toward clinically relevant measurement times.
Surgical Metastasectomy in the Spine: A Review Article
Authors: Kato Satoshi , Demura Satoru , Shinmura Kazuya , Yokogawa Noriaki , Shimizu Takaki , Murakami Hideki , Kawahara Norio , Tomita Katsuro , Tsuchiya Hiroyuki
Published: June 2021

Background

The use of surgical metastasectomy (SM) has increased across cancer types in recent decades despite the increasing efficacy of modern systemic treatment modalities. Symptomatic spinal metastases severely compromise patients’ performance status. However, as spinal SM is a complex surgery with potentially significant complications, it is not considered the treatment of choice.

Methods

We reviewed the articles on SM in several primary cancers with different types of metastatic lesions and extracted the data from relevant articles to provide a comprehensive review including the surgical techniques, indications, reported outcomes, and future prospects of SM in spinal metastases.

Results

Total en bloc spondylectomy (TES) is a method of spinal SM associated with a lower risk of tumor recurrence and complications. Intralesional transpedicular osteotomy using a fine threadwire saw allows prevention of spinal cord and nerve root injuries. Spinal SM is considered suitable for patients with controlled primary disease having no evidence of disseminated extraspinal metastases, a completely resectable solitary lesion in the spine, and adequate cardiopulmonary reserve to tolerate the surgery. Metastatic lesions from kidney and thyroid cancers have been reported as the best candidates for spinal SM. Although data about spinal SM are limited, the reported outcomes are favorable with acceptable local recurrence rates in long-term follow-up.

Conclusion

In patients with isolated resectable spinal metastases, complete SM including TES is a useful option as it can improve function and survival. However, appropriate patient selection and surgical feasibility remain the most important aspects of management.

Implications for Practice

Surgical metastasectomy for spinal metastases may be a potentially curative treatment option with a low risk of local recurrence and lead to prolonged long-term survival if appropriate patients are selected and if the surgery is carried out by experienced surgeons in high-volume centers.
Population pharmacokinetics of belantamab mafodotin, a BCMA‐targeting agent in patients with relapsed/refractory multiple myeloma
Authors: Rathi Chetan , Collins Jon , Struemper Herbert , Opalinska Joanna , Jewell Roxanne C. , Ferron‐Brady Geraldine
Published: June 2021

Belantamab mafodotin (belamaf) is an antibody–drug conjugate (ADC) targeting B‐cell maturation antigen (BCMA). Nonlinear mixed‐effects models were developed to characterize the population pharmacokinetics (PopPK) of ADC, total monoclonal antibody (mAb), and cysteine‐maleimidocaproyl‐MMAF (cys‐mcMMAF) after 0.03–4.6 mg/kg dosing every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM; DREAMM‐1, n = 73; DREAMM‐2, n = 218). Sequential modeling methodology was used. Individual post hoc parameter estimates from the final ADC model were used to develop total mAb and cys‐mcMMAF models. Formal covariate selection used a modified stepwise forward inclusion method with backward elimination. A linear, two‐compartment PopPK model with a time‐varying clearance (CL) described ADC PK. Initial ADC typical value for CL for a DREAMM‐2 patient was 0.936 L/day with a half‐life of 11.5 days, over time CL was reduced by 28% resulting in a half‐life of 14.3 days. Time to 50% maximal CL change was ~ 50 days. Baseline soluble BCMA (sBCMA), immunoglobulin (IgG), albumin, and bodyweight impacted ADC CL. Cys‐mcMMAF concentrations were described with a linear two‐compartment model linked to ADC; input rate was governed by deconjugation/intracellular proteolytic degradation of ADC represented by an exponentially decreasing MMAF:mAb (drug antibody ratio [DAR]) after each dose. Time to 50% DAR reduction was 10.3 days. Baseline sBCMA and IgG impacted cys‐mcMMAF central volume of distribution. In conclusion, ADC, total mAb, and cys‐mcMMAF concentration–time profiles in RRMM were well‐described by PopPK models, and exposure was most strongly impacted by disease‐related characteristics.
A Theoretical Investigation of the Stability, Electronic, Optical, and Thermoelectric Properties of BaLiP
Authors: Dusabe Bonaventure , Dongho-Nguimdo Guy Moise , Mohammed Hamza A. H. , Joubert Daniel P.
Published: June 2021

The density functional theory and post density functional theory techniques are used to investigate the properties of BaLiP for potential applications in photovoltaic and thermoelectric (TE) applications. Density functional calculations of the cohesive energy, phonon‐dispersion, and elastic constant studies establish structural, dynamical, and mechanical stability of the compound. Density functional calculations show that BaLiP is a direct bandgap semiconductor while optical properties at the Bethe–Salpeter equation level of approximation suggest that BaLiP is anisotropic with the optical bandgaps of and  eV for in‐plane and out‐of‐plane absorption, respectively. A maximum absorption coefficient of   for in‐plane and   for out‐of‐plane absorption in the visible range at and  eV is found, respectively. Lattice thermal conductivity is computed using a Boltzmann transport equation approach. The calculations reveal that the average lattice thermal conductivity is   at room temperature. The figure of merit, which is the main criterion for estimating the TE potential of a material, is estimated to have a maximum of at 1000 K at a hole carrier concentration of  . This study shows that BaLiP has some promise as a candidate for applications in electronics, optoelectronics, and TE applications.
Efficiency Limits in Wide‐Bandgap Ge‐Containing Donor Polymer:Nonfullerene Acceptor Bulk Heterojunction Solar Cells
Authors: Alsaggaf Sarah , Ashraf Raja Shahid , Purushothaman Balaji , Chaturvedi Neha , McCulloch Iain , Laquai Frédéric , Khan Jafar Iqbal
Published: June 2021

A precise picture of the photophysics that determine the efficiency of nonfullerene acceptor (NFA) bulk heterojunction (BHJ) organic solar cells is still missing, yet needed to mitigate the remaining loss channels. Herein, charge carrier generation and recombination dynamics in blends of a novel wide‐bandgap germanium‐containing donor polymer, namely, PEHGeNDT‐BT, paired with either O‐IDTBR or O‐IDTBCN as NFA in BHJ solar cells are investigated by (ultrafast) transient spectroscopy and time‐delayed collection field (TDCF) experiments. Photovoltaic devices yield moderate power conversion efficiencies (PCEs) of 5.3% when using O‐IDTBCN as the acceptor, and only about 2% when using O‐IDTBR as the acceptor, the latter severely limited by its low photocurrent and moderate fill factor (FF) of ≈43%. Time‐resolved photoluminescence experiments reveal limited exciton quenching as one loss channel in O‐IDTBR‐based blends, accompanied by significant geminate recombination further reducing the photocurrent, while field‐dependent charge generation is identified as the origin of the low FF. Geminate recombination is less in the O‐IDTBCN blend and charge generation is field‐independent, leading to improved photocurrent and FF. Carrier drift‐diffusion simulations of the devices’ current–voltage (J–V) characteristics confirm that the experimentally determined kinetic parameters and process yields can reproduce the measured J–V curves under steady‐state solar illumination.
Which patents to use as loan collaterals? The role of newness of patents' external technology linkage
Authors: Zhang Yan Anthea , Chen Zhuo Emma , Wang Yuandi
Published: June 2021

Research Summary

Patent collateral is an important aspect in the debt financing of firms. We argue that in accepting patent collaterals, lenders need to balance between risk of obsolescence and risk of unverified external inventions, both of which are related to patents' external technology linkage. Patents linked to old external inventions are subject to risk of obsolescence while patents linked to too new external inventions are subject to risk of unverified external inventions, and therefore we propose patents linked to moderately new external inventions are more likely to be pledged. We further propose the turning point of this curvilinear relationship depends on borrowing firms' attributes: firm‐specificity of their patent assets and their technological specialization domains. Using data on 107,180 U.S. semiconductor patents, our results support these propositions.

Managerial Summary

Patent collateralization represents an important innovation in the debt market. Then, how to choose appropriate patents as collaterals is an important question for patenting firms and financial institutions accepting patents as collaterals. Our results suggest that patents linked to old external inventions are less likely to be pledged because such patents may become obsolete soon, patents linked to too new external inventions are also less likely to be pledged because such patents may be deemed too risky, and patents linked to moderately new external inventions are more likely to pledged. We further find that lenders' concerns on risk of unverified external inventions become more salient if borrowing firms' inventions are more firm‐specific but become less so if borrowing firms specialize in the patents' technological domains.
Engineering local coordination environments and site densities for high‐performance Fe‐N‐C oxygen reduction reaction electrocatalysis
Authors: Wang Qing , Shang Lu , Sun‐Waterhouse Dongxiao , Zhang Tierui , Waterhouse Geoffrey
Published: June 2021

Fe‐N‐C catalysts represent very promising cathode catalysts for polymer electrolyte fuel cells, owing to their outstanding activity for the oxygen reduction reaction (ORR), especially in alkaline media. In this review, we summarize recent advances in the design and synthesis of Fe‐N‐C catalysts rich in highly dispersed FeN
x
active sites. Special emphasis is placed on emerging strategies for tuning the electronic structure of the Fe atoms to enhance the ORR activity, and also maximizing the surface concentration of FeN
x
sites that are catalytically accessible during ORR. While great progress has been made over the past 5 years in the development of Fe‐N‐C catalyst for ORR, significant technical obstacles still need to be overcome to enable the large‐scale application of Fe‐N‐C materials as cathode catalysts in real‐world fuel cells.
Effect of spent engine oil contamination on the soil properties in selected automobile mechanic villages in Enugu, Enugu State, Nigeria
Authors: Echiegu Emmanuel A. , Amadi Adaugo S. , Ugwuishiwu Boniface O. , Nwoke Oji A.
Published: June 2021

This study was carried out to determine the effect of spent engine oil on the soil properties in selected automobile mechanic villages in Enugu, Enugu State, Nigeria. Spent engine oil (SEO) was collected and characterized according to ASTM test methods. Soil samples were collected at 0–30 and 30–60 cm depths from the mechanic villages and uncontaminated agricultural farmlands 500 m away as control and properties analyzed. The extent of contamination of heavy metals in soils was assessed. The results of the SEO characterization showed the values of 2.87 wt%, 218°C, 13.18 mg/kg, 0.75 mg/kg, 4.06 mg/kg, and 0.94 mg/kg for toluene insoluble, flash point, Pb, As, Cr and Cd. The soil bulk density, pH, TOC, TOM, N, P, Cu, Cd, Pb, and Fe decreased with increasing depth while particle density, TSP, S, Cr, and As increased with increasing depth. The ANOVA results showed that a statistically significant difference existed between values of soil parameters (p < 0.05), indicating that SEO has a significant effect on soil properties (α = 0.05). The study will provide useful insights for developing a precautionary strategy and inform environmental policy implementation for an effective risk management approach in the study area.
Optimal Supportive Measures during Primary Treatment
Authors: Bossi Paolo , Lorini Luigi
Published: June 2021

Supportive care during curative treatment of head and neck cancer patients has different scopes: reducing the burden of acute toxicities and limiting the risk of developing late adverse effects; increasing the quality of life of the patients; allowing to perform optimal curative therapy, maintaining treatment dose intensity; preventing higher grade toxicities so to reduce also the costs associated with hospitalization, examinations, visits and use of drugs. At the same time, it is necessary to give uniformity in the supportive care protocols, as these preventive and therapeutic measures may influence the results of oncological treatments and their efficacy should be evaluated in a consistent manner. Several preventive and therapeutic interventions are available, particularly in the context of chemoradiotherapy, where the adverse events are more prominent. An accurate evaluation of the patient and a tailored approach with preventative indications and therapeutic interventions represent key factors. This approach could be easily identified within a “simultaneous care” strategy, as the optimal supportive measures are provided concurrently to the best therapeutic approach since the beginning of the treatment.
Salvage Surgery in Head and Neck Cancer
Authors: van Weert Stijn , Parmar Sat , Leemans C. René
Published: June 2021

Salvage surgery (SS) in head and neck cancer is considered a last resort treatment after failure of organ preservation treatments. It offers challenges to the patients and the surgeon. The outcome of SS is often uncertain in terms of survival and quality of life. This paper offers an overview of evolution in SS, tumor and patient factors to be considered, challenges in reconstructive surgery, complications of SS and the changing landscape with regard to increasing incidence of human papillomavirus positive tumours, the role of transoral robotic surgery, the importance of multidisciplinary management and shared decision making.
New and Promising Targeted Therapies in First and Second-Line Settings
Authors: Roden Dylan F. , Johnson Jennifer M. , Szturz Petr , Bossi Paolo , Argiris Athanassios
Published: June 2021

Deeper understanding of the molecular pathogenesis of malignancies, including head and neck squamous cell carcinoma (HNSCC), has led to the investigation of several novel targeted therapies. These therapeutic approaches may eventually replace or complement existing treatment modalities, such as surgery, radiation therapy, and traditional cytotoxic chemotherapy. Epidermal growth factor receptor (EGFR) inhibitors, and specifically cetuximab, are as of now the only class of targeted agents, excluding immune checkpoint inhibitors, with approval in the treatment of HNSCC. Beyond EGFR inhibition, novel therapies under evaluation are directed against vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR), PI3K/AKT/mTOR pathway, cell cycle regulation (for example, cyclin dependent kinases 4 and 6), HRAS, DNA repair mechanisms, and others. Development of new therapies has to take into consideration the complexity of solid tumors and their heterogeneity. Multitargeted combination therapy approaches may be required in certain cases in order to maximize antitumor effect. Ways to individualize treatment using validated biomarkers are likely to improve outcomes. We review the most relevant molecular targets in HNSCC and provide updates on clinical trial data with promising new targeted agents.