bluuebunny/crossref_metadata_2025 huggingface dataset:
Gab1 mediates PDGF signaling and is essential to oligodendrocyte differentiation and CNS myelination
Authors: Zhou Liang , Shao Chong-Yu , Xie Ya-Jun , Wang Na , Xu Si-Min , Luo Ben-Yan , Wu Zhi-Ying , Ke Yue Hai , Qiu Mengsheng , Shen Ying
Published: January 2020

Oligodendrocytes (OLs) myelinate axons and provide electrical insulation and trophic support for neurons in the central nervous system (CNS). Platelet-derived growth factor (PDGF) is critical for steady-state number and differentiation of oligodendrocyte precursor cells (OPCs), but its downstream targets are unclear. Here, we show for the first time that Gab1, an adaptor protein of receptor tyrosine kinase, is specifically expressed in OL lineage cells and is an essential effector of PDGF signaling in OPCs in mice. Gab1 is downregulated by PDGF stimulation and upregulated during OPC differentiation. Conditional deletions of Gab1 in OLs cause CNS hypomyelination by affecting OPC differentiation. Moreover, Gab1 binds to downstream GSK3β and regulated its activity, and thereby affects the nuclear accumulation of β-catenin and the expression of a number of transcription factors critical to myelination. Our work uncovers a novel downstream target of PDGF signaling, which is essential to OPC differentiation and CNS myelination.
Synthesis and biological activity of 1,4-pentadien-3-one derivatives containing triazine scaffolds
Authors: Tang Xu , Chen Mei , He Jun , Su Shijun , Xia Rongjiao , Guo Tao , Jiang Shichun , Liu Liwei , Xue Wei
Published: January 2020

Background

Literatures revealed that 1,4-pentadien-3-one and triazine derivatives exhibited a wide variety of biological activities. In order to develop highly bioactive molecules, in this study, a series of novel 1,4-pentadien-3-one derivatives containing triazine moieties were synthesized and their antibacterial and antiviral activities were investigated.

Methods

A series of novel 1,4-pentadien-3-one derivatives containing triazine moieties were synthesized and characterized in detail via 1H NMR, 13C NMR and HRMS spectra. The antibacterial activities against Xanthomonas axonopodispv. citri (Xac), Xanthomonas oryzaepv. oryzae (Xoo) and Ralstonia solanacearum (R.s) were evaluated at 100 and 50 µg/mL using a turbidimeter and N. tabacun L. leaves under the same age as that of test subjects. The curative, protective and inactivation activities against tobacco mosaic virus (TMV) at a concentration of 500 µg/mL were evaluated via the half-leaf blight spot method.

Results

The bioassay results showed that some of the target compounds exhibited fine antibacterial activities against Xac and R.s. Particularly, half maximal effective concentration (EC50) values of some target compounds against R.s are visibly better than that of the positive control bismerthiazol (BT). Notably, compound 4a showed excellent inactivation activity against TMV with a EC50 value of 12.5 µg/mL, which was superior to that ofningnanmycin (NNM,13.5 µg/mL). Besides, molecular docking studies for 4awith tobacco mosaic virus coat protein (TMV-CP) showed that the compound was embedded well in the pocket between the two subunits of TMV-CP. These findings indicate that 1,4-pentadien-3-one derivatives containing triazine moieties may be potential antiviral and antibacterial agents.
Application of problem-based learning and case-based learning integrated method in the teaching of maxillary sinus floor augmentation in implant dentistry
Authors: Liu Yunfei , Xu Yamei , Li Yueheng , Wu Qingqing
Published: January 2020

Background

Teaching of maxillary sinus floor augmentation (MSFA) is challenging for dental educators due to the varied sinus anatomy and high rate of complications. The method integrating problem-based learning and case-based learning (PBL-CBL method) may be more effective than the traditional teacher-centered method. The aim is to evaluate the efficacy of the PBL-CBL method in teaching MSFA.

Materials & Methods

Ninety-two students who received training between 2015 and 2017 at the Department of Implant Dentistry were divided randomly into an experimental group and a control group. Students in the experimental group were trained using the PBL-CBL method, while those in the control group were trained using the traditional teacher-centered method. After three months of training, a survey of the students’ opinions about the corresponding teaching method was carried out through a feedback questionnaire. A theory test was used to investigate the level of MSFA knowledge among the students. A case analysis was designed to test whether the students can apply the knowledge in solving new problems.

Results

Compared with the control method, the PBL-CBL method resulted in higher scores in both the theory test and the case analysis, and obtained a higher rate of satisfaction among the students. The difference in scores between the two methods were statistically significant (P < 0.01),

Conclusion

The PBL-CBL method resulted in better results regarding acquisition of academic knowledge, ability in case analysis and student satisfaction compared with the teacher-centered method. It may be a promising mode for teaching complex surgical techniques in implant dentistry and other dental fields.
Retargeting adenoviruses for therapeutic applications and vaccines
Authors: Barry Michael A. , Rubin Jeffrey D. , Lu Shao‐Chia
Published: January 2020

Adenoviruses (Ads) are robust vectors for therapeutic applications and vaccines, but their use can be limited by differences in their in vitro and in vivo pharmacologies. This review emphasizes that there is not just one Ad, but a whole virome of diverse viruses that can be used as therapeutics. It discusses that true vector targeting involves not only retargeting viruses, but importantly also detargeting the viruses from off‐target cells.
Cannabinoids and Their Receptors
Authors: Straiker Alex
Published: January 2020

Phytocannabinoids are ∼100 molecules with a similar structural motif found in cannabis. The best known of these is Δ
9
‐tetrahydrocannabinol (Δ
9
‐THC), the chief psychoactive component of cannabis. In 1989, the first ‘cannabinoid’ receptor was identified. This first receptor, christened CB1, has since been joined by several others: CB2, GPR18 and GPR119. These receptors mediate the effects of THC but are also part of an endogenous signalling system. The human body makes endogenous cannabinoids; lipid messengers that are structurally distinct from phytocannabinoids and that are synthesised and metabolised enzymatically. This combination of cannabinoid receptors, endocannabinoids and proteins to synthesise, transport and metabolise these receptors form an important endogenous signalling system with roles in the brain and throughout the body. The cannabinoid signalling system regulates numerous functions including memory, motor control, appetite, nausea and pain.

Key Concepts

Δ
9
‐THC is a plant cannabinoid that acts on the body by plugging into an endogenous signalling system in the body.

Δ
9
‐THC is one of ∼100 ‘phytocannabinoids’ including cannabidiol (CBD) that are an area of active research.

Established cannabinoid receptors are G‐protein‐coupled receptors (GPCRs) that transmit an extracellular chemical signal into an intracellular cascade via second messengers.

Cannabinoid receptors are found in much of the brain and throughout the body where they play numerous physiological roles.

Endogenous cannabinoids are lipid messengers that are structurally unrelated to Δ
9
‐THC.

Unlike classical neurotransmitters, endocannabinoids are not stored in or released from vesicles but are instead produced ‘on‐demand’ and subsequently metabolised by enzymes.

Cannabinoid enzymes synthesise or metabolise families of cannabinoid‐related lipids rather than a single endocannabinoid.

The ubiquity of cannabinoid receptors in the body and the legal status of cannabinoids have made development of cannabinoid‐based therapeutics difficult.
Clinical Genetics of Cholangiopathies
Authors: Reichert Matthias Christian , Lammert Frank
Published: January 2020

Cholestasis can be caused by various liver diseases. In the recent years, genetic factors for cholestatic liver diseases have been identified. In the case of rare cholestatic liver diseases such as progressive familial intrahepatic cholestasis, genetic tests are already an indispensable part of the diagnostic algorithm. Frequently the causative gene mutations lead to the dysfunction of hepatocanalicular transporters. The further development of genetic testing (gene panels, exome sequencing) will help to tailor the treatment of patients with inherited cholestatic liver diseases.

Key Concepts

For ‘classic’ cholestatic liver diseases such as PBC and PSC or drug‐induced cholestasis, genetic risk factors have been identified, but these are not yet helpful for clinical routine.

In monogenic cholestasis syndromes, causative mutations in genes coding for hepatocanalicular transporter can be identified in many patients by gene sequencing.

Clinical phenotypes, γ‐GT and liver biopsy are helpful in the differential diagnosis of the different FIC subtypes.

ABCB4 deficiency due to variants in this gene encoding the hepatocanalicular phosphatidylcholine transporter is characterised by a broad clinical spectrum, ranging from ICP to LPAC to the severe phenotype PFIC.

Through genetics‐based diagnosis (gene panel, exome sequencing), previously unknown gene variants can be identified in individual patients with cholestatic liver diseases of unknown aetiology. However, the interpretation of the results and the functional relevance can be challenging.
Optically Inspired Nanomagnonics with Nonreciprocal Spin Waves in Synthetic Antiferromagnets
Authors: Albisetti Edoardo , Tacchi Silvia , Silvani Raffaele , Scaramuzzi Giuseppe , Finizio Simone , Wintz Sebastian , Rinaldi Christian , Cantoni Matteo , Raabe Jörg , Carlotti Giovanni , Bertacco Riccardo , Riedo Elisa , Petti Daniela
Published: January 2020

Integrated optically inspired wave‐based processing is envisioned to outperform digital architectures in specific tasks, such as image processing and speech recognition. In this view, spin waves represent a promising route due to their nanoscale wavelength in the gigahertz frequency range and rich phenomenology. Here, a versatile, optically inspired platform using spin waves is realized, demonstrating the wavefront engineering, focusing, and robust interference of spin waves with nanoscale wavelength. In particular, magnonic nanoantennas based on tailored spin textures are used for launching spatially shaped coherent wavefronts, diffraction‐limited spin‐wave beams, and generating robust multi‐beam interference patterns, which spatially extend for several times the spin‐wave wavelength. Furthermore, it is shown that intriguing features, such as resilience to back reflection, naturally arise from the spin‐wave nonreciprocity in synthetic antiferromagnets, preserving the high quality of the interference patterns from spurious counterpropagating modes. This work represents a fundamental step toward the realization of nanoscale optically inspired devices based on spin waves.
Highly Thermoconductive, Thermostable, and Super‐Flexible Film by Engineering 1D Rigid Rod‐Like Aramid Nanofiber/2D Boron Nitride Nanosheets
Authors: Wu Kai , Wang Jiemin , Liu Dingyao , Lei Chuxin , Liu Dan , Lei Weiwei , Fu Qiang
Published: January 2020

Polymer‐based thermal management materials have many irreplaceable advantages not found in metals or ceramics, such as easy processing, low density, and excellent flexibility. However, their limited thermal conductivity and unsatisfactory resistance to elevated temperatures (<200 °C) still prevent effective heat dissipation during applications with high‐temperature conditions or powerful operation. Therefore, herein highly thermoconductive and thermostable polymer nanocomposite films prepared by engineering 1D aramid nanofiber (ANF) with worm‐like microscopic morphologies into rigid rod‐like structures with 2D boron nitride nanosheets (BNNS) are reported. With no coils or entanglements, the rigid polymer chain enables a well‐packed crystalline structure resulting in a 20‐fold (or greater) increase in axial thermal conductivity. Additionally, strong interfacial interactions between the weaved ANF rod and the stacked BNNS facilitate efficient heat flux through the 1D/2D configuration. Hence, unprecedented in‐plane thermal conductivities as high as 46.7 W m−1 K−1 can be achieved at only 30 wt% BNNS loading, a value of 137% greater than that of a worm‐like ANF/BNNS counterpart. Moreover, the thermally stable nanocomposite films with light weight (28.9 W m−1 K−1/103 (kg m−3)) and high strength (>100 MPa, 450 °C) enable effective thermal management for microelectrodes operating at temperatures beyond 200 °C.
Ultrasmall BiOI Quantum Dots with Efficient Renal Clearance for Enhanced Radiotherapy of Cancer
Authors: Wang Xin , Guo Zhao , Zhang Chenyang , Zhu Shuang , Li Lele , Gu Zhanjun , Zhao Yuliang
Published: January 2020

Emerging strategies involving nanomaterials with high‐atomic‐number elements have been widely developed for radiotherapy in recent years. However, the concern regarding their potential toxicity caused by long‐term body retention still limits their further application. In this regard, rapidly clearable radiosensitizers are highly desired for practical cancer treatment. Thus, in this work, ultrasmall BiOI quantum dots (QDs) with efficient renal clearance characteristic and strong permeability inside solid tumor are designed to address this issue. Additionally, considering that injection methods have great influence on the biodistribution and radiotherapeutic efficacy of radiosensitizers, two common injection methods including intratumoral injection and intravenous injection are evaluated. The results exhibit that intratumoral injection can maximize the accumulation of radiosensitizers within a tumor compared to intravenous injection and further enhance radiotherapeutic efficacy. Furthermore, the radiosensitizing effect of BiOI QDs is revealed, which is not only attributed to the radiation enhancement of high‐Z elements but also is owed to the •OH production via catalyzing overexpressed H2O2 within a tumor by BiOI QDs under X‐ray irradiation. As a result, this work proposes a treatment paradigm to employ ultrasmall radiosensitizers integrated with local intratumoral injection to realize rapid clearance and high‐efficiency radiosensitization for cancer therapy.
Ultrastrong and Highly Sensitive Fiber Microactuators Constructed by Force‐Reeled Silks
Authors: Lin Shihui , Wang Zhen , Chen Xinyan , Ren Jing , Ling Shengjie
Published: January 2020

Fiber microactuators are interesting in wide variety of emerging fields, including artificial muscles, biosensors, and wearable devices. In the present study, a robust, fast‐responsive, and humidity‐induced silk fiber microactuator is developed by integrating force‐reeling and yarn‐spinning techniques. The shape gradient, together with hierarchical rough surface, allows these silk fiber microactuators to respond rapidly to humidity. The silk fiber microactuator can reach maximum rotation speed of 6179.3° s−1 in 4.8 s. Such a response speed (1030 rotations per minute) is comparable with the most advanced microactuators. Moreover, this microactuator generates 2.1 W kg−1 of average actuation power, which is twice higher than fiber actuators constructed by cocoon silks. The actuating powers of silk fiber microactuators can be precisely programmed by controlling the number of fibers used. Lastly, theory predicts the observed performance merits of silk fiber microactuators toward inspiring the rational design of water‐induced microactuators.
Quantification of palmer amaranth seed number using a computerized particle analyzer
Authors: Bertucci Matthew B. , Bartley Paul C. , Jennings Katherine M. , Monks David W. , Jackson Brian E.
Published: January 2020

We evaluated the accuracy of a computerized particle analyzer (CPA) for high‐throughput counting of Palmer amaranth (Amaranthus palmeri S. Watson) seeds and subsequently used the CPA to verify the accuracy of two subsampling methods for estimation of Palmer amaranth seed production. To determine accuracy of the CPA, 55 hand‐counted samples, ranging from 500 to 5000 Palmer amaranth seeds, were drawn from field samples and counted with the CPA. The relationship between hand and CPA seed counts was described by a linear model (R2 = 0.99) with a slope of 0.987 and a y‐intercept of 3.49. Thus, very little discrepancy exists between seed counts conducted by hand or the CPA. Additionally, two published methods for estimation of Palmer amaranth seed production were compared to the CPA and proven to be highly accurate. We conclude from these findings that the CPA offers a high‐throughput alternative for weed scientists who frequently count large quantities of seed.
High and Temperature‐Independent Dielectric Constant Dielectrics from PVDF‐Based Terpolymer and Copolymer Blends
Authors: Thuau Damien , Kallitsis Konstantinos , Ha Sara , Bargain François , Soulestin Thibaut , Pecastaings Gilles , Tencé‐Girault Sylvie , Domingues Dos Santos Fabrice , Hadziioannou Georges
Published: January 2020

Relaxor ferroelectric polymers exhibit high k at their structural phase transition around room temperature. They are particularly attractive as gate dielectric in organic field effect transistor (OFET). Nevertheless, their applications are limited due to their low thermal stability. A polymer blend system with a high and thermally stable dielectric constant is demonstrated by mixing terpolymer poly(vinylidene fluoride‐trifluoroethylene‐chlorofluorethylene) P(VDF‐ter‐TrFE‐ter‐CFE) with copolymer poly(vinylidene fluoride‐trifluoroethylene) P(VDF‐co‐TrFE). PVDF‐based blends of various compositions are characterized by dielectric spectroscopy, differential scanning calorimetry (DSC), infrared spectroscopy, small and wide angle X‐ray scattering (SAXS and WAXS), and atomic force microscopy (AFM) in order to investigate the relationship between morphology and crystallization of the blend and their dielectric properties. An optimized blend of P(VDF‐ter‐TrFE‐ter‐CFE) [55/37/8] and P(VDF‐co‐TrFE) [46/54] at a ratio of 70/30 is found to exhibit a quasi‐constant dielectric constant of 40 ± 2 over a wide temperature range (20–80 °C). Furthermore, electrical characteristics of the PVDF‐blend‐based gate dielectric OFET show further thermal stability in comparison to OFET based on high‐k terpolymer P(VDF‐ter‐TrFE‐ter‐CFE) [55/37/8]. An improvement of their drain current stability by up to 60% is demonstrated at 60 °C. These findings enable broader applications of fluoropolymers in organic electronics.
Comparison of four warm‐season turfgrass species to natural rainfall or supplemental irrigation in a semiarid climate
Authors: Culpepper Travis , Young Joseph , Wherley Benjamin
Published: January 2020

Increased urban populations and drought conditions strain municipal water supplies, often resulting in activation of water conservation plans. Supplemental irrigation can be eliminated in extreme situations, which diminishes functional and visual benefits of turfgrass landscapes. The objective of this research was to evaluate differential responses of four warm‐season turfgrasses receiving supplemental irrigation (subsurface drip) or natural rainfall only in semiarid climate. Celebration bermudagrass [Cynodon dactylon (L.) Pers.] and Legacy buffalograss [Buchloe dactyloides (Nutt.) Engelm.] were sodded in 2014; Jamur Japanese lawngrass (Zoysia japonica Steud.) and Zeon Manilagrass [Zoysia matrella (L.) Merr.] were sodded in 2016. Species were split with mowing treatments at 5 or 9 cm. Limited mowing effects on response variables led to pooling mowing heights for species. Supplemental irrigation supplied 69 and 173 mm of water from July to September in 2017 and 2018, respectively. Volumetric water content (VWC) in the upper 3.8 cm, canopy temperature, normalized difference vegetation index (NDVI), and visual turf quality were recorded weekly. Drought stress symptoms were evident both years. Manilagrass experienced greatest drought stress, which lowered NDVI and turf quality with significant canopy temperature increase in 2017. Bermudagrass maintained lowest canopy temperature with greatest NDVI and turf quality with natural rainfall each year. Supplemental irrigation was required to lower canopy temperature and enhance NDVI and turf quality for other species. Results suggest bermudagrass maintains best functional and aesthetic quality under 123 mm rainfall. Japanese lawngrass and buffalograss improved with supplemental irrigation, but Manilagrass required supplemental irrigation to provide acceptable quality.
Effects of growth‐promoting bacteria on soybean root activity, plant development, and yield
Authors: Moretti Luiz Gustavo , Crusciol Carlos A. C. , Kuramae Eiko E. , Bossolani João W. , Moreira Adônis , Costa Nídia R. , Alves Cleiton J. , Pascoaloto Isabô M. , Rondina Artur B. L. , Hungria Mariangela
Published: January 2020

Rhizobia and other plant growth‐promoting rhizobacteria (PGPR) have been broadly used as inoculants in agriculture, resulting in morphofunctional improvements in roots and grain yield. This study was carried out during two cropping seasons under field and greenhouse conditions in Brazil to verify the effects of inoculation of two soybean cultivars with PGPR and secondary microbial metabolites (SMMs) on root activity and nodulation, plant development, and grain yield. Inoculation and co‐inoculation treatments consisted of Bradyrhizobium japonicum strain SEMIA 5079 and B. diazoefficiens strain SEMIA 5080 inoculated together, in combination with Bacillus subtilis strain QST 713, Azospirillum brasilense strains Ab‐V5 and Ab‐V6, and SMMs extracted from B. diazoefficiens strain USDA 110 and Rhizobium tropici strain CIAT 889. Root systems were evaluated by direct (optical reading) and indirect (rubidium nitrate application, 85RbNO3) methods. Increases of up to 1.6% in root diameter (0.01‐ to 0.5‐mm class), 28.5% in length, 19.7% in root volume, 17.8% in root surface area, 29% in the number of nodules, 27.2% in nodule dry weight, 13.5% in root dry weight, and 3.8% in shoot dry weight. Greater exploration and activity within and between rows following inoculation at up to 40 and 10 cm in depth, respectively, were observed in plants co‐inoculated with the standard inoculation (only Bradyrhizobium spp.) + SMMs + A. brasilense, resulting in a yield increase of 485 kg ha−1. The results emphasize the biotechnological potential of using secondary metabolites of rhizobia with inoculants containing rhizobia and PGPR to improve the growth and soybean yield in tropical conditions.
Resilience, Coloniality, and Sovereign Acts: The Role of Community Activism
Authors: Serrano‐García Irma
Published: January 2020

Puerto Rico has been a U.S. colony since 1898. For the past decades, it has been mired in public debt, social problems, and ineffective and corrupt governance. In 2017, the island was hit by hurricanes which devastated our country. After the event, the term “resilience” became ubiquitous. Labeling Puerto Ricans’ capacity to tolerate misfortune and suffering “resilient” gave people a false sense of hope and offered government a pretext to postpone or inequitably dispense aid. So‐called “resilience” also allowed Puerto Ricans to avoid the impact of colonialism and coloniality on pre‐existing conditions which hurricanes accentuated. In this context, community activism played a major role. Community organizations initially provided aid and generated chains of solidarity. They initiated “sovereign acts” which are mostly guided by principles and values espoused by community psychology. Thus, we have a duty to contribute to efforts which can promote liberating our island from colonialism and coloniality.
Forest fragments become farmland: Dietary Response of wild chimpanzees (Pan troglodytes) to fast‐changing anthropogenic landscapes
Authors: McLennan Matthew R. , Lorenti Georgia A. , Sabiiti Tom , Bardi Massimo
Published: January 2020

Behavioral flexibility, including an ability to modify feeding behavior, is a key trait enabling primates to survive in forest fragments. In human‐dominated landscapes, unprotected forest fragments can become progressively degraded, and may be cleared entirely, challenging the capacity of primates to adjust to the changes. We examined responses of wild chimpanzees (Pan troglodytes schweinfurthii) to major habitat change: that is, clearance of forest fragments for agriculture. Over 7 years, fragments in Bulindi, Uganda, were reduced in size by 80%. We compared the chimpanzees’ diet at the start and end of this period of rapid deforestation, using data derived mainly from fecal analysis. Similar to other long‐term study populations, chimpanzees in Bulindi have a diverse diet comprising over 169 plant foods. However, extensive deforestation seemed to impact their feeding ecology. Dietary changes after fragment clearance included reduced overall frugivory, reduced intake of figs (Ficus spp.; formerly a dietary “staple” for these chimpanzees), and reduced variety of fruits in fecal samples. Nevertheless, the magnitude of most changes was remarkably minor given the extent of forest loss. Agricultural fruits increased in dietary importance, with crops accounting for a greater proportion of fruits in fecal samples after deforestation. In particular, cultivated jackfruit (Artocarpus heterophyllus) became a “staple” food for the chimpanzees but was scarcely eaten before fragment clearance. Crops offer some nutritional benefits for primates, being high in carbohydrate energy and low in hard‐to‐digest fiber. Thus, crop feeding may have offset foraging costs associated with loss of wild foods and reduced overall frugivory for the chimpanzees. The adaptability of many primates offers hope for their conservation in fragmented, rural landscapes. However, long‐term data are needed to establish whether potential benefits (i.e. energetic, reproductive) of foraging in agricultural matrix habitats outweigh fitness costs from anthropogenic mortality risk for chimpanzees and other adaptable primates.
Concordance of Lumipulse cerebrospinal fluid t‐tau/Aβ42 ratio with amyloid PET status
Authors: Kaplow June , Vandijck Manu , Gray Julia , Kanekiyo Michio , Huyck Els , Traynham C. J. , Esquivel Rianne , Fagan Anne M. , Luthman Johan
Published: January 2020

Introduction

Cerebrospinal fluid (CSF) biomarkers can identify individuals with Alzheimer's disease (AD) pathology (eg, amyloid plaques, neurofibrillary tangles), but defined analyte cut‐points using high‐throughput automated assays are necessary for general clinical use.

Methods

CSF amyloid β42 peptide (Aβ42), t‐tau, and t‐tau/Aβ42 were quantified by the Lumipulse platform in two test cohorts (A/B: Eisai BAN2401‐201/MISSION AD E2609‐301/302, n = 138; C: Knight Alzheimer's Disease Research Center (ADRC), n = 198), and receiver operating characteristic (ROC) curve analyses defined cut‐points corresponding best to amyloid determinations using positron emission tomography (PET) imaging. The best‐performing cut‐point was then validated as a predictor of amyloid status in an independent cohort (D: MISSION AD E2609‐301/302, n = 240).

Results

Virtually identical t‐tau/Aβ42 cut‐points (∼0.54) performed best in both test cohorts and with similar accuracy (areas under ROC curve [AUCs] [A/B: 0.95; C: 0.94]). The cut‐point yielded an overall percent agreement with amyloid PET of 85.0% in validation cohort D.

Discussion

Lumipulse CSF biomarker measures with validated cut‐points have clinical utility in identifying AD pathology.
Long‐term case study of a Wuzhishan miniature pig with diabetes
Authors: Niu Miaomiao , Liu Yaqian , Xiang Lei , Zhao Yuqiong , Yuan Jifang , Jia Yunxiao , Dai Xin , Chen Hua
Published: January 2020

Background

Miniature pigs are attractive animal models for exploring diabetes because they are similar to humans in terms of physiological structure and metabolism. However, little is known about the complications of diabetes in pigs.

Methods

In this study, a 28‐month observation of a Wuzhishan miniature pig with streptozotocin (STZ)‐induced (120 mg/kg) diabetes was conducted, to investigate diabetes‐related complications and the possibility of self‐recovery in miniature pigs. Blood glucose, serum and urinary biochemistry was measured, and histopathologic examinations of eyes, kidney and pancreas were made.

Results

During the observation, diabetic complications of eyes and kidney were observed. The eye complications included bilateral cataracts in the 15th month and degeneration of inner retina and microaneurysm in the 28th month. Kidney complications included glomerular mesangial expansion, focal segmental glomerular sclerosis, and renal tubular epithelial degeneration, but no proteinuria was observed. By 28 months after the application of STZ, with no treatment given, blood glucose had recovered and the number of pancreatic islet beta‐cells had increased significantly.

Conclusions

We showed that the STZ‐induced diabetes model in miniature pigs could accurately mimic the pathological changes of human diabetes, and that pancreatic islet beta‐cell regeneration did occur in an adult miniature pig, providing a new means for exploring diabetic complications and pancreatic islet beta‐cell regeneration.
Anticoagulant therapy for septic coagulopathy and disseminated intravascular coagulation: where do KyberSept and SCARLET leave us?
Authors: Wiedermann Christian J.
Published: January 2020

The use of antithrombin and thrombomodulin to restore impaired anticoagulant pathways in septic coagulopathy has been shown to significantly increase the resolution rate of disseminated intravascular coagulation. In KyberSept and SCARLET, two large, international, randomized controlled trials in patients with sepsis, these anticoagulants have not shown significantly reduced mortality. The aim of this assessment was to compare the heterogeneity in responses to treatment in the two trials according to different patient phenotypes. Results of the KyberSept and SCARLET trials reported in original and post‐hoc publications were analyzed and directly compared for treatment effects in various patient subgroups. In both KyberSept and SCARLET, the septic coagulopathy phenotype that benefited most from endogenous anticoagulant supplementation showed markers of excessive activation of coagulation. Interaction between concomitant thromboprophylactic heparin and the endogenous anticoagulants abrogated the efficacy of both antithrombin and thrombomodulin. In both trials, higher disease severity was associated with better treatment outcome. In conclusion, in two landmark studies of endogenous anticoagulants in patients with sepsis, similar findings of beneficial effects in the coagulopathy phenotype and interactions with heparin comedication and disease severity support the potential roles that thrombomodulin and antithrombin might play in treating septic coagulopathy and disseminated intravascular coagulation. Further prospective validation is warranted. Future trial designs to definitively establish the therapeutic relevance of antithrombin and thrombomodulin in septic coagulopathy should focus on involvement of patients characterized by coagulopathy and disease severity as well as interactions between endogenous anticoagulants and exogenous heparin.
Stable Polymer Nanoparticles with Exceptionally High Drug Loading by Sequential Nanoprecipitation
Authors: Liu Yun , Yang Guangze , Baby Thejus , Tengjisi  , Chen Dong , Weitz David A. , Zhao Chun‐Xia
Published: January 2020

Poor solubility often leads to low drug efficacy. Encapsulation of water‐insoluble drugs in polymeric nanoparticles offers a solution. However, low drug loading remains a critical challenge. Now, a simple and robust sequential nanoprecipitation technology is used to produce stable drug‐core polymer‐shell nanoparticles with high drug loading (up to 58.5 %) from a wide range of polymers and drugs. This technology is based on tuning the precipitation time of drugs and polymers using a solvent system comprising multiple organic solvents, which allows the formation of drug nanoparticles first followed by immediate precipitation of one or two polymers. This technology offers a new strategy to manufacture polymeric nanoparticles with high drug loading having good long‐term stability and programmed release and opens a unique opportunity for drug delivery applications.
Remote Participation during Glycosylation Reactions of Galactose Building Blocks: Direct Evidence from Cryogenic Vibrational Spectroscopy
Authors: Marianski Mateusz , Mucha Eike , Greis Kim , Moon Sooyeon , Pardo Alonso , Kirschbaum Carla , Thomas Daniel A. , Meijer Gerard , von Helden Gert , Gilmore Kerry , Seeberger Peter H. , Pagel Kevin
Published: January 2020

The stereoselective formation of 1,2‐cis‐glycosidic bonds is challenging. However, 1,2‐cis‐selectivity can be induced by remote participation of C4 or C6 ester groups. Reactions involving remote participation are believed to proceed via a key ionic intermediate, the glycosyl cation. Although mechanistic pathways were postulated many years ago, the structure of the reaction intermediates remained elusive owing to their short‐lived nature. Herein, we unravel the structure of glycosyl cations involved in remote participation reactions via cryogenic vibrational spectroscopy and first principles theory. Acetyl groups at C4 ensure α‐selective galactosylations by forming a covalent bond to the anomeric carbon in dioxolenium‐type ions. Unexpectedly, also benzyl ether protecting groups can engage in remote participation and promote the stereoselective formation of 1,2‐cis‐glycosidic bonds.
Influence of the morphology and viscoelasticity on the thermomechanical properties of poly(lactic acid)/thermoplastic polyurethane blends compatibilized with ethylene‐ester copolymer
Authors: Bernardes Giordano Pierozan , da Rosa Luiz Nathália , Santana Ruth Marlene Campomanes , de Camargo Forte Maria Madalena
Published: January 2020

Viscoelastic, interfacial properties, and morphological data were employed to predict the thermal and mechanical properties of compatibilized poly(lactic acid) (PLA)/thermoplastic polyurethane (TPU) blends. The combination of interfacial thickness measured by contact angle and entanglement density determined by dynamical mechanical analysis analyze data was employed to evaluate the mechanical behavior of PLA/TPU blends with and without ethylene‐butyl acrylate‐glycidyl methacrylate (EBG) compatibilization agent. The PLA/TPU blend (70/30 wt %) was prepared in a Haake internal mixer at 190 °C and compatibilized with different contents of EBG. The evaluation of the interfacial properties revealed an increase in the interfacial layer thickness of the PLA/TPU blend with EBG. The scanning electronic microscopy images showed a drastic reduction in the size of the dispersed phase by increasing the compatibilizer agent EBG content in the blend. The compatibilization of the PLA/TPU blends improved both the Izod impact strength and yield stress by 38 and 33%, respectively, in comparison with neat PLA/TPU blend. The addition of EBG into PLA/TPU blends significantly increased the entanglement density and the PLA toughening but resulted in a decrease of PLA deformation at break. The PLA and TPU glass transitions were affected by the EBG, suggesting that the PLA and TPU domains were partially miscible. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48926.
Excellent oil/water separation performance of poly(styrene‐alt‐maleic anhydride)/fluorocarbon surfactant membrane filter with functionalized multiwalled carbon nanotubes
Authors: Guo Ya‐Ni , Liang Li‐Yun , Bao Shi‐Xuan , Du Fei‐Peng , Wen Xuan
Published: January 2020

Polymer/fluorocarbon surfactant membranes have been reported to display excellent oleophobic/hydrophilic behavior and outstanding oil/water separation properties. In this work, multiwalled carbon nanotubes (MWNTs) enhanced poly(styrene‐alt‐maleic anhydride)/fluorocarbon surfactant (PSMA/MWNTs/FS) membrane filters were prepared by dip‐coating PSMA/MWNTs/FS on stainless steel meshes for efficient oil/water separation. The microstructure, thermal properties, wettability, oil/water separation ability, and recyclability were investigated. The results revealed that the MWNTs are suitably dispersed in the membrane, further increasing the thermal stability, oil/water separation efficiency, and recyclability. The oil/water separation efficiency of the complex membrane filter containing MWNTs was 99% initially and 97% after 20 cycles. This work provides a simple, low‐cost, and environmentally friendly approach for efficient oil/water separation.
Cost‐effectiveness analysis of pembrolizumab plus chemotherapy with PD‐L1 test for the first‐line treatment of NSCLC
Authors: Wan Ning , Zhang Tian‐tian , Hua Si‐hua , Lu Zi‐luo , Ji Bo , Li Li‐xia , Lu Li‐qing , Huang Wen‐jie , Jiang Jie , Li Jian
Published: January 2020

Background

Pembrolizumab (Pembro) in combination with chemotherapy has been approved for the treatment of pretreated advanced NSCLC in the United States and China for its significant efficacy. However, the cost‐effectiveness is unknown considering Pembro's high price. The impact of programmed death ligand 1 (PD‐L1) test on the cost‐effectiveness is also unknown. The current study assessed the cost‐effectiveness of combination therapy for nonsquamous NSCLC from the United States and China public payers’ perspective.

Materials and Methods

A literature‐based Markov model was conducted using KEYNOTE‐189 trial data to compare cost and quality‐adjusted life years (QALYs) of three treatment strategies for nonsquamous NSCLC: Pembro‐chemotherapy combination and chemotherapy strategy without PD‐L1 test, and treatment strategy according to their PD‐L1 status.

Results

In base case analysis, the combination strategy generated an additional 0.78 QALYs and 0.59 QALYs over chemotherapy in the United States and China respectively, resulting in an ICER of $132 392/QALY in the United States and $92 533/QALY in China. In the PD‐L1 ≥1% base case, the ICERs were $77 754/QALY and $56 768/QALY respectively in the United States and China for PD‐L1 test strategy. In the PD‐L1 ≥50% base case, the ICERs were $44 731/QALY and $34 388/QALY respectively in the United States and China for PD‐L1 test strategy. Lowering Pembro price can also partly decrease the ICERs.

Conclusion

Compared with chemotherapy, the combination strategy is not cost‐effective for the treatment of NSCLC in the American and Chinese health care system at WTP threshold of $100 000/QALY for the United States and $27 351/QALY for China. Using PD‐L1 test for patient selection and price reduction could improve the cost‐effective probabilities of immunotherapy for nonsquamous NSCLC.
Self‐Healing Microsupercapacitors with Size‐Dependent 2D MXene
Authors: Li Xingxing , Ma Yanan , Shen Peizhi , Zhang Chuankun , Yan Jinfeng , Xia Yingbo , Luo Shijun , Gao Yihua
Published: January 2020

Very recently, 2D MXene has attracted a lot of attention in energy storage, due to its large specific surface area, good hydrophilicity, good conductivity and adjustable composition. Herein, we reported a kind of self‐healing microsupercapacitors (MSCs) based on size‐dependent Ti3C2Tx MXene. Due to the rich physicochemical properties of Ti3C2Tx, the MSCs were fabricated by firstly spraying different lateral size MXene nanosheets onto the cellulose paper, and then selectively engraving interdigital electrodes by laser engraving machine. The flexible MXene‐based MSCs were assembled by sulfuric acid‐polyvinyl alcohol electrolyte. It is observed the electrochemical performance of MXene‐based MSCs is significantly affected by the nanosheet size. And the capacitance of MSCs fabricated by smaller lateral nanosheet reached up to 73.6 mF/cm2, which is higher than that of the larger lateral nanosheet and mixture one that contains smaller and larger nanosheets (1 : 1 mass ratio). Moreover, the self‐healing MXene‐based MSCs fabricated with polyurethane containing large number of hydrogen bonds as the wrapped material, present an excellent self‐healing ability with capacitance retention of 90 % over 2000 charge/discharge cycles after 5th cutting/healing. And MXene‐based MSCs display great potential in the field of energy storage, which not only turn on the LED light but also drive the electronic clock.
Enantiomers of phospholipids and cholesterol: A key to decipher lipid‐lipid interplay in membrane
Authors: Hanashima Shinya , Yano Yo , Murata Michio
Published: January 2020

Most phospholipids constituting biological membranes are chiral molecules with a hydrophilic head group and hydrophobic alkyl chains, rendering biphasic property characteristic of membrane lipids. Some lipids assemble into small domains via chirality‐dependent homophilic and heterophilic interactions, the latter of which sometimes include cholesterol to form lipid rafts and other microdomains. On the other hand, lipid mediators and hormones derived from chiral lipids are recognized by specific membrane or nuclear receptors to induce downstream signaling. It is crucial to clarify the physicochemical properties of the lipid self‐assembly for the study of the functions and behavior of biological membranes, which often become elusive due to effects of membrane proteins and other biological events. Three major lipids with different skeletal structures were discussed: sphingolipids including ceramides, phosphoglycerolipids, and cholesterol. The physicochemical properties of membranes and physiological functions of lipid enantiomers and diastereomers were described in comparison to natural lipids. When each enantiomer formed a self‐assembly or interacted with achiral lipids, both lipid enantiomers exhibited identical membrane physicochemical properties, while when the enantiomer interacted with chiral lipids or with the opposite enantiomer, mixed membranes exhibited different properties. For example, racemic membranes comprising native sphingomyelin and its antipode exhibited phase segregation due to their strong homophilic interactions. Therefore, lipid enantiomers and diastereomers can be good probes to investigate stereospecific lipid‐lipid and lipid‐protein interactions occurring in biological membranes.
One‐Pot Process to Carborano‐Coumarin via Catalytic CascadeDehydrogenative Cross‐Coupling
Authors: Au Yik Ki , Lyu Hairong , Quan Yangjian , Xie Zuowei
Published: January 2020

Summary of main observation and conclusion

Ir‐catalyzed cascade dehydrogenative CH/BH and BH/OH cross‐coupling of carboranyl carboxylic acid with readily available benzoic acid has been achieved, leading to the facile synthesis of previously unavailable carborano‐coumarin in a simple one‐pot process. Two cage B—H, one aryl C—H and one O—H bonds are activated to construct efficiently new B—C and B—O bonds. The cascade cyclization can stop at the first B—H/C—H cross‐coupling step by tuning the reaction conditions, resulting in a series of α‐carboranyl benzoic acid and aryl carborane derivatives. Control experiments indicate that B—H/C—H dehydrocoupling proceeds preferentially over B—H/O—H dehydrocoupling, and both directing groups and oxidants are crucial for this reaction. An iridium(V) intermediate is proposed to be involved in the catalytic cycle.
Biomechanical analysis of the interaction phenomena between artificial urinary sphincter and urethral duct
Authors: Natali Arturo N. , Fontanella Chiara G. , Carniel Emanuele L.
Published: January 2020

Male urinary incontinence is a widespread healthcare problem, leading to a miserable quality of life. Artificial urinary sphincter (AUS) is a device inserted mostly around the urethra in adult males, which mimics the urinary sphincter by providing a closure during urinary storage and a subsequent open to permit voiding. The interaction phenomena occurring between AUS cuff and urethral duct represent a fundamental problem in the investigation of AUS reliability and durability. In this work, computational methods are exploited to deeply investigate the mechanics of interaction phenomena occurring between urethral duct and AUS device. Experimental studies are performed on urethral tissues, and structural tests are carried out on the overall urethral duct to obtain a large set of information required for mechanical properties definition. The mechanical behavior of AUS cuff is investigated using mechanical and physicochemical procedures. The cuff conformation is acquired by computed tomography techniques for the definition of the numerical model. Numerical analyses are developed to evaluate the mechanical response of urethral duct in interaction with AUS cuff, considering the lumen occlusion process for maintaining urinary continence. Finally, the investigation of the compressive stress and strain fields within urethral tissues allows the identification of device performance and reliability in correlation with surgical practice.
Visible‐Light‐Triggered Quantitative Oxidation of 9,10‐Dihydroanthracene to Anthraquinone by O2 under Mild Conditions
Authors: Jiang Dabo , Hu Wenwei , Chen Mengke , Fu Zaihui , Su Anqun , Yang Bo , Mao Feng , Zhang Chao , Liu Yachun , Yin Dulin
Published: January 2020

The development of mild and efficient processes for the selective oxygenation of organic compounds by molecular oxygen (O2) is key for the synthesis of oxygenates. This paper discloses an atom‐efficient synthesis protocol for the photo‐oxygenation of 9,10‐dihydroanthracene (DHA) by O2 to anthraquinone (AQ), which could achieve quantitative AQ yield (100 %) without any extra catalysts or additives under ambient temperature and pressure. A yield of 86.4 % AQ was obtained even in an air atmosphere. Furthermore, this protocol showed good compatibility for the photo‐oxidation of several other compounds with similar structures to DHA. From a series of control experiments, free‐radical quenching, and electron paramagnetic resonance spin‐trapping results, the photo‐oxygenation of DHA was probably initiated by its photoexcited state DHA*, and the latter could activate O2 to a superoxide anion radical (O2.−) through the transfer of its electron. Subsequently, this photo‐oxidation was gradually dominated by the oxygenated product AQ as an active photocatalyst obtained from the oxidation of DHA by O2.−, and was accelerated with the rapid accumulation of AQ. The present photo‐oxidation protocol is a good example of selective oxygenation based on the photoexcited substrate self‐activated O2, which complies well with green chemistry ideals.
An Evaluation of T‐Cell Functionality After Flow Cytometry Sorting Revealed p38 MAPK Activation
Authors: Andrä Immanuel , Ulrich Hanna , Dürr Susi , Soll Dominik , Henkel Lynette , Angerpointner Corinne , Ritter Julia , Przibilla Sabine , Stadler Herbert , Effenberger Manuel , Busch Dirk H. , Schiemann Matthias
Published: January 2020

Cell alterations during isolation and preparation for flow cytometry cell sorting by antibodies, temperature, homogenization, buffer composition and mitogens are well known. In contrast, little is known about cell alteration caused by the instrument or the sorting process itself. We systematically evaluated cellular responses to different sorter‐induced physical forces. In summary, flow cytometry cell‐sorting induced forces can affect cellular signaling cascades, especially the MAPK p38. Functional assays, related to the p38 MAPK pathway, of human primary T cells after flow cytometry sorting did lead to minor physiological modulation but no functional impairments. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.