bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from "Winter is Coming – Temperature Affects Immune Defenses and Susceptibility to Batrachochytrium salamandrivorans"
Authors: Matthew Gray
Published: January 2021

Environmental temperature is a key factor driving various biological processes, including immune defenses and host-pathogen interactions. Here, we evaluated the effects of environmental temperature on the pathogenicity of the emerging fungus, Batrachochytrium salamandrivorans (Bsal), using controlled laboratory experiments, and measured components of host immune defense to identify regulating mechanisms. We found that adult and juvenile Notophthalmus viridescens died faster due to Bsal chytridiomycosis at 14 ºC than at 6 and 22 ºC. Pathogen replication rates, total available proteins on the skin, and microbiome composition likely drove these relationships. Temperature-dependent skin microbiome composition in our laboratory experiments matched seasonal trends in wild N. viridescens, adding validity to these results. We also found that hydrophobic peptide production after two months post-exposure to Bsal was reduced in infected animals compared to controls, perhaps due to peptide release earlier in infection or impaired granular gland function in diseased animals. Using our temperature-dependent infection results, we performed a geographic analysis that suggested that N. viridescens populations in the northeastern United States and southeastern Canada are at greatest risk for Bsal invasion. Our results indicate that environmental temperature will play a key role in the epidemiology of Bsal and provide evidence that temperature manipulations may be a viable Bsal management strategy.
Protagonismo Indígena: arranjos e conflitos nas sesmarias dos jesuítas
Authors: Barros Rafael dos Santos
Published: January 2021

Essa obra procura compreender a atuação de um grupo indígena na Capitania dos Ilhéus durante a primeira metade do século XVII. As áreas possíveis para alimentação e caça foram tomadas pelas ocupações dos não índios, reduzindo as possibilidades dos povos indígenas viverem de acordo com seus hábitos. Inseridos nesse ambiente, estavam os índios Guerens, os quais usando a tutela de um capitão-mor conseguiram livrarem-se da opressão e tornarem-se súditos do rei de Portugal, permitindo-lhes sobreviv
New combination for Uncinia flaccida in Carex (Cyperaceae)
Authors: Wilson Karen L.
Published: January 2021

A new combination in Carex is made for Uncinia flaccida S.T.Blake since the earlier name Carex flaccida Sw. ex Wahlenb. is a nomen nudum.
Fetal Autopsy Showing Two Ventral Body Wall Defects: An Unusual Presentation
Authors: Kaur Anupriya , Prasad Arun , Pushpaja Jessy Jayaraman , Kapoora Kanchan
Published: January 2021

Thoracoschisis and gastroschisis are types of ventral body wall defects. Usually thoracoabdominoschisis presents as a continuous defect. Here the authors present the case of autopsy of 18 weeks old fetus with two well-separated ventral body wall defects. Thoracoschisis was a right lateral thoracic wall defect while gastroschisis, a midline infraumblical abdominal wall defect. Through the right lateral thoracic wall parts of two organs appeared to be protruding. On dissection, 8th and 9th ribs with the liver and the lower lobe of the right lung were herniating outside the body. The right lung was haemorrhagic. Various embryological theories on ventral body wall defects have been discussed in view of the present case.
Prevalence of Non-autoimmune Hypothyroidism in Steroid Resistant Nephrotic Syndrome in Paediatric Age Group
Authors: Sinha Seema Rani , Kumari Rekha , Kumar Rakesh , Shekhar Ravi , Prakash Pritam , Prakash Prem
Published: January 2021

Introduction: It was observed that approximately 10% of children with Nephrotic Syndrome (NS) are found as Steroid Resistant NS (SRNS). The data on the prevalence of non-autoimmune hypothyroidism among the SRNS in India is limited. Aim: To assess the prevalence of non-autoimmune hypothyroidism in the case of SRNS. Materials and Methods: A case control cross-sectional study was conducted in which 52 cases of SRNS and 52 healthy controls were enrolled. Thyroid profile like serum Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (T3), Free Thyroxine (T4) done in the all cases and controls but anti-Thyroid Peroxidase (TPO), and anti-thyroglobulin antibody test was done in the case and control group with deranged thyroid function test. Low Free T4 (normal: 0.7-2 ng/mL) and elevated serum TSH above the upper limit of the reference range (>4.5 mIU/L) was defined as overt hypothyroidism, whereas elevation in serum TSH with a normal serum FT4 concentration was defined as sub clinical hypothyroidism. MedCalc statistical software Version 19.2.6 was used to do statistical analysis. Results: Prevalence of Non-autoimmune hypothyroidism was 38.46% (20 out of 52), 16 (30.76%) had subclinical and 4 (7.69%) had overt hypothyroidism in case of SRNS in comparison to 1.96% (1 out of 52) in control group. Out of 16 subclinical hypothyroid patients, two cases with grade 1, 12 cases with grade 2, and two cases with grade 3 found. Patients with SRNS had a mean (SD) TSH value of 4.5±4.7 mlU/L which was significantly higher than control (1.8±1.1 mlU/L). Serum levels of FT4 were within normal range. Anti-TPO and anti-thyroglobulin titre were in normal range in children with hypothyroidism. Conclusion: The prevalence of non-autoimmune hypothyroidism was high in cases of idiopathic SRNS. So, on the basis of this study estimation of thyroid profile in children with SRNS seems to be the rational approach which will lead to early diagnosis and timely management of hypothyroidism in SRNS.
ESTIMATING THE UNDERESTIMATION PROFILE OF HEALTH SERVICE NEEDS THROUGH TELEPHONE COUNSELING CENTERS
Authors: Guimarães Junior Djalma Silva , Melo Fagner José Coutinho de , Sant’anna Carlos Henrique Michels de , Soares Eduardo José Oenning , Ferraz Júnior Gileno , Medeiros Denise Dumke de
Published: January 2021

The public and private health systems around the world face an expansion of services in parallel with the demand for improved quality and cost savings. Quality and efficiency of such systems are affected by the underestimation of the needs for patient care, compromising the clinical condition of the patient and system costs. The objective of this study is to identify the factors that determine the underestimation of the need for health services in Brazil. The survey used data collected from medical advice call center reports, totaling 19.690 observations; 2.166 of these have involved underestimation of needs, wherein the complexity of the intention of the patient is smaller than the recommendation proposed by the physician, which is divided into very or less critical. Through a logistic regression model, it was possible to estimate the critical factors in determining the underestimation in very and less critical needs for health services in Brazil. The closeness to the weekend increases the probability of a very critical underestimation. Daytime hours feature a very critical underestimation tendency. In terms of age groups, we can see a probability of very critical underestimation in younger individuals. This study showed that the user profile that was most likely to have very critical underestimation of the demand for health care was that of the underage individual who calls on weekends and in the early hours of the day.
Structural snapshots of the kinesin‐2 OSM‐3 along its nucleotide cycle: implications for the ATP hydrolysis mechanism
Authors: Varela Paloma F. , Chenon Mélanie , Velours Christophe , Verhey Kristen J. , Ménétrey Julie , Gigant Benoît
Published: January 2021

Motile kinesins are motor proteins that translocate along microtubules as they hydrolyze ATP. They share a conserved motor domain which harbors both ATPase and microtubule‐binding activities. An ATP hydrolysis mechanism involving two water molecules has been proposed based on the structure of the kinesin‐5 Eg5 bound to an ATP analog. Whether this mechanism is general in the kinesin superfamily remains uncertain. Here, we present structural snapshots of the motor domain of OSM‐3 along its nucleotide cycle. OSM‐3 belongs to the homodimeric kinesin‐2 subfamily and is the Caenorhabditis elegans homologue of human KIF17. OSM‐3 bound to ADP or devoid of a nucleotide shows features of ADP‐kinesins with a docked neck linker. When bound to an ATP analog, OSM‐3 adopts a conformation similar to those of several ATP‐like kinesins, either isolated or bound to tubulin. Moreover, the OSM‐3 nucleotide‐binding site is virtually identical to that of ATP‐like Eg5, demonstrating a shared ATPase mechanism. Therefore, our data extend to kinesin‐2 the two‐water ATP hydrolysis mechanism and further suggest that it is universal within the kinesin superfamily.

Protein Database entries

7A3Z, 7A40, 7A5E.
Typological study of Oya stone buildings and townscapes: A case study of Nishine District, Tokujirou Town, Utsunomiya City
Authors: Yasumori Akio
Published: January 2021

The Japanese style of architecture has traditionally been centered on wood; however, stone from the surrounding regions has also been used as a construction material in some instances. In a volcanically active country like Japan, tuff originating from solidified volcanic ash, is quite common. The tuff, thanks to its low specific gravity and softness, is easier to process. Oya stone, a kind of tuff predominantly found in Utsunomiya City (Tochigi Prefecture, approximately 100 km north of Tokyo), has been utilized as a building material. In this study, the typology of stone buildings and townscapes in the Nishine District of Tokujirou Town is elucidated. Tokujira stone, which is similar to Oya stone, was quarried here earlier. First, 62 stone buildings at 22 sites in the district were identified, which were subsequently classified into eight types according to the construction method (such as piling stones, cladding stones, and foundation stones), as well as the use of the buildings (such as storehouses and residences). Second, the site composition was analyzed according to the building layout and its relationship with the primary highway. For this purpose, three characteristic townscape types were identified, which reflect the local architectural culture, materials, and technique.
Polyarteritis Nodosa: A Systematic Review of Test Accuracy and Benefits and Harms of Common Treatments
Authors: Lin Yih Chang , Kalot Mohamad A. , Husainat Nedaa M. , Byram Kevin , Dua Anisha B. , James Karen E. , Springer Jason M. , Turgunbaev Marat , Villa‐Forte Alexandra , Abril Andy , Langford Carol , Maz Mehrdad , Chung Sharon A. , Mustafa Reem A.
Published: January 2021

Objective

The object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with primary systemic polyarteritis nodosa (PAN).

Methods

A systematic search of published English‐language literature was performed in Ovid Medline, PubMed, Embase, and the Cochrane Library from the inception of each database through August 2019. Articles were screened for suitability in addressing patient, intervention, comparison, and outcome questions, with studies presenting the highest level of evidence given preference.

Results

Of 137 articles selected for data abstraction, we analyzed 21 observational studies and seven randomized controlled trials (RCTs). The results showed indirect evidence that a deep skin biopsy provides good diagnostic accuracy. A combined nerve and muscle biopsy should be obtained for patients with PAN with peripheral neuropathy. Cyclophosphamide with high‐dose glucocorticoids (GCs) is effective as an induction treatment for newly diagnosed active and severe PAN. GC monotherapy is adequate in the majority of patients with nonsevere PAN, although it has a high relapse rate with GC taper. There was insufficient data in determining the optimal duration of non‐GC and GC maintenance therapy. Tumor necrosis factor inhibitors are effective treatment for patients with deficiency of adenosine deaminase 2 (DADA2) with stroke and vasculitis manifestations.

Conclusion

This comprehensive systematic review synthesizes and evaluates the harms and benefits of different treatment options and the accuracy of commonly used tests for the diagnosis of systemic PAN. Data for diagnosis and management of PAN and DADA2 are mostly limited to observational studies. More high‐quality RCTs are needed.
Manipulating the Crystallization Kinetics by Additive Engineering toward High‐Efficient Photovoltaic Performance
Authors: Song Jingnan , Hu Qin , Zhang Quanzeng , Xiong Shaobing , Zhao Zhe , Ali Jazib , Zou Yecheng , Feng Wei , Yang Zhibin , Bao Qinye , Zhang Yongming , Russell Thomas P. , Liu Feng
Published: January 2021

Additive processing is proven to be an effective method to improve the efficiency and stability of perovskite solar cells; however, its intrinsic role in directing the crystallization pathway and thus morphology formation remains unknown. In situ grazing‐incidence wide‐angle x‐ray scattering (GIWAXS) is applied to study the function of a 1,8‐diiodooctane (DIO) additive in manipulating the crystallization behavior of perovskite thin films. It is seen that the DIO additive could induce multi‐stage intermediate crystallization phases and increases the activation energy for nucleation and growth, which postpones the perovskite phase transformation time and broadens the transition zone. The elongated crystallization process affords improved perovskite thin film crystallinity and reduces defect density, which enables a longer carrier diffusion length. As a result, improved device efficiency, moisture, and thermal stability can be achieved. The current study provides a new prospective in understanding the additive function in perovskite thin film morphology control from fundamental parameters, indicating the importance of minor processing conditions in global property management toward high device performance.
Cell‐Laden Gradient Hydrogel Scaffolds for Neovascularization of Engineered Tissues
Authors: He Yusheng J. , Santana Martin F. , Staneviciute Austeja , Pimentel Marja B. , Yang Feipeng , Goes Jacob , Kawaji Keigo , Vaicik Marcella K. , Abdulhadi Rayan , Hibino Narutoshi , Papavasiliou Georgia
Published: January 2021

Gradients in mechanical properties, physical architecture and biochemical composition exist in a variety of complex tissues, yet 3D in vitro models that enable investigation of these cues on cellular processes, especially those contributing to vascularization of engineered tissues are limited. Here, a photopolymerization approach to create cell‐laden hydrogel biomaterials with decoupled and combined gradients in modulus, immobilized cell adhesive peptide (RGD) concentration, and proteolytic degradation enabling spatial encapsulation of vascular spheroids is reported to elucidate their impact on vascular sprouting in 3D culture. Vascular spheroids encapsulated in these gradient scaffolds exhibit spatial variations in total sprout length. Scaffolds presenting an immobilized RGD gradient promote biased vascular sprouting toward increasing RGD concentration. Importantly, biased sprouting is found to be dependent on immobilized RGD gradient characteristics, including magnitude and slope, with increases in these factors contributing to significant enhancements in biased sprouting responses. Conversely, reduction in biased sprouting responses is observed in combined gradient scaffolds possessing opposing gradients in RGD and modulus. The presented work is the first to demonstrate the use of a cell‐laden biomaterial platform to systematically investigate the role of multiple scaffold gradients as well as gradient slope, magnitude and orientation on vascular sprouting responses in 3D culture.
2D Nanomaterials for Tissue Engineering and Regenerative Nanomedicines: Recent Advances and Future Challenges
Authors: Zheng Yuanyuan , Hong Xiangqian , Wang Jiantao , Feng Longbao , Fan Taojian , Guo Rui , Zhang Han
Published: January 2021

Regenerative medicine has become one of the hottest research topics in medical science that provides a promising way for repairing tissue defects in the human body. Due to their excellent physicochemical properties, the application of 2D nanomaterials in regenerative medicine has gradually developed and has been attracting a wide range of research interests in recent years. In particular, graphene and its derivatives, black phosphorus, and transition metal dichalcogenides are applied in all the aspects of tissue engineering to replace or restore tissues. This review focuses on the latest advances in the application of 2D‐nanomaterial‐based hydrogels, nanosheets, or scaffolds that are engineered to repair skin, bone, and cartilage tissues. Reviews on other applications, including cardiac muscle regeneration, skeletal muscle repair, nerve regeneration, brain disease treatment, and spinal cord healing are also provided. The challenges and prospects of applications of 2D nanomaterials in regenerative medicine are discussed.
Photocrosslinked, Tunable Protein Vesicles for Drug Delivery Applications
Authors: Li Yirui , Champion Julie A.
Published: January 2021

Recombinant proteins have emerged as promising building blocks for vesicle self‐assembly because of their versatility through genetic manipulation and biocompatibility. Vesicles composed of thermally responsive elastin‐like polypeptide (ELP) fusion proteins encapsulate cargo during assembly. However, vesicle stability in physiological environments remains a significant challenge for biofunctional applications. Here, incorporation of an unnatural amino acid, para‐azido phenylalanine, into the ELP domain is reported to enable photocrosslinking of protein vesicles and tuning of vesicle size and swelling. The size of the vesicles can be tuned by changing ELP hydrophobicity and ionic strength. Protein vesicles are assessed for their ability to encapsulate doxorubicin and dually deliver doxorubicin and fluorescent protein in vitro as a proof of concept. The resulting photocrosslinkable vesicles made from full‐sized, functional proteins show high potential in drug delivery applications, especially for small molecule/protein combination therapies or targeted therapies.
Realizing an All‐Round Hydrogel Electrolyte toward Environmentally Adaptive Dendrite‐Free Aqueous Zn–MnO2 Batteries
Authors: Chen Minfeng , Chen Jizhang , Zhou Weijun , Han Xiang , Yao Yagang , Wong Ching‐Ping
Published: January 2021

Flexible energy storage devices are at the forefront of next‐generation power supplies, one of the most important components of which is the gel electrolyte. However, shortcomings exist, more or less, for all the currently developed hydrogel electrolytes. Herein, a facile and cost‐effective method is developed to construct an all‐round hydrogel electrolyte by using cotton as the raw material, tetraethyl orthosilicate as the crosslinker, and glycerol as the antifreezing agent. The obtained hydrogel electrolyte has high ionic conductivity, excellent mechanical properties (e.g., high tensile strength and elasticity), ultralow freezing point, good self‐healing ability, high adhesion, and good heat‐resistance ability. Remarkably, this hydrogel electrolyte can provide a record‐breaking high ionic conductivity of 19.4 mS cm−1 at −40 °C compared with previously reported aqueous electrolytes for zinc‐ion batteries. In addition, this hydrogel electrolyte can significantly inhibit zinc dendritic growth and parasitic side reactions from −40 to 60 °C. With this hydrogel electrolyte, a flexible quasi‐solid‐state Zn–MnO2 battery is assembled, which shows remarkable energy densities from −40 to 60 °C. The battery also exhibits outstanding cycling durability and has high endurance under various harsh conditions. This work opens new opportunities for the development of hydrogel electrolytes.
Increasing the Possibilities of TEMPO‐Mediated Oxidation in the Production of Cellulose Nanofibers by Reducing the Reaction Time and Reusing the Reaction Medium
Authors: Sanchez‐Salvador Jose Luis , Campano Cristina , Negro Carlos , Monte M. Concepcion , Blanco Angeles
Published: January 2021

2,2,6,6‐Tetramethylpiperidine‐1‐oxyl (TEMPO)‐mediated oxidation of cellulose is the most effective pretreatment to obtain highly fibrillated cellulose nanofibers (CNFs). However, the associated environmental impact and the high operational costs have limited its implementation at large scale. This study aims to improve the effectiveness of this pretreatment by reducing the oxidation time and reusing the reaction medium, with the ultimate objective of upscaling a more viable sustainable process. The results show the possibility of reducing the reaction time by 85% and 60% in the case of cotton and eucalyptus pulps, respectively, without altering the properties of the obtained CNFs (carboxyl groups, nanofibrillation yield, cationic demand, and morphology). The reuse of 75% of the reaction medium for ten cycles, do not alter the properties of the CNFs either. With this approach, the consumption of TEMPO and NaBr is reduced by 67%, while that of NaClO is decreased by 42% and 22% in the oxidation of cotton and eucalyptus cellulose, respectively. At the same time, the environmental concerns derived from the disposal of the catalysts are considerably reduced.
Generation of Nanodroplet Reactors and Their Applications in In Situ Controllable Synthesis and Transportation of Ag Nanoparticles
Authors: Lin Guanhua , Wang Haifei , Lu Wensheng
Published: January 2021

Nanodroplets have been paid great attention as they are crucial for a wide range of physical, chemical, and biological applications. In this paper, monodispersed nanodroplets are prepared and their directed motions are realized through conducting the formation of nonuniform structures via altering the ionic distribution within; all these dynamics have been observed by using in situ transmission electron microscopy liquid cell technology. It has been found that their transformation from random motion to directed motion is reversible. Moreover, combining multiple directed motions enables long‐distance travel with directed motion taking up 95% of the total time. The results here also prove that aqueous nanodroplets can slide directionally on the hydrophilic surface like droplets sliding on hydrophobic surface. Furthermore, the authors successfully achieve the unidirectional transportation of in situ prepared Ag nanoparticles by using the nanodroplets as nanoreactor, carrier, and transporter. The size and number of as‐prepared Ag nanoparticles can be quantitatively controlled. In summary, this research provides a new strategy for real‐time generation and precise manipulation of aqueous nanodroplets. Together with the quantitatively controllable in situ synthesis of Ag nanoparticles within the nanodroplets, this work can prove their promising applications in many fields.
PADI2‐Catalyzed MEK1 Citrullination Activates ERK1/2 and Promotes IGF2BP1‐Mediated SOX2 mRNA Stability in Endometrial Cancer
Authors: Xue Teng , Liu Xiaoqiu , Zhang Mei , E Qiukai , Liu Shuting , Zou Maosheng , Li Ying , Ma Zhinan , Han Yun , Thompson Paul , Zhang Xuesen
Published: January 2021

Peptidylarginine deiminase II (PADI2) converts positively charged arginine residues to neutrally charged citrulline, and this activity has been associated with the onset and progression of multiple cancers. However, a role for PADI2 in endometrial cancer (EC) has not been previously explored. This study demonstrates that PADI2 is positively associated with EC proregression. Mechanistically, PADI2 interacting and catalyzing MEK1 citrullination at arginine 113/189 facilitates MEK1 on extracellular signal‐regulated protein kinases 1/2 (ERK1/2) phosphorylation, which activates insulin‐like growth factor‐II binding protein 1 (IGF2BP1) expression. Furthermore, RNA immunoprecipitation (RIP) and RNA stability analyses reveal that IGF2BP1 binds to the m6A sites in SOX2‐3′UTR to prevent SOX2 mRNA degradation. Dysregulation of IGF2BP1 by PADI2/MEK1/ERK signaling results in abnormal accumulation of oncogenic SOX2 expression, therefore supporting the malignant state of EC. Finally, PADI2 gene silencing, inhibiting MEK1 citrullination by PADI2 inhibitor, or mutation of MEK1 R113/189 equally inhibits EC progression. These data demonstrate that PADI2‐catalyzed MEK1 R113/189 citrullination is a critical diver for EC malignancies and suggest that targeting PADI2/MEK1 can be a potential therapeutic approach in patients with EC.
Promoting the Reversible Oxygen Redox Reaction of Li‐Excess Layered Cathode Materials with Surface Vanadium Cation Doping
Authors: Lee Yongju , Shin Jaewook , Kang Hyeonmuk , Lee Daehee , Kim Tae‐Hee , Kwon Young‐Kyun , Cho EunAe
Published: January 2021

Li‐excess layered cathode (LLC) materials have a high theoretical specific capacity of 250 mAh g−1 induced by transition metal (cationic) and oxygen (anionic) redox activity. Especially, the oxygen redox reaction related to the activation of the Li2MnO3 domain plays the crucial role of providing a high specific capacity. However, it also induces an irreversible oxygen release and accelerates the layered‐to‐spinel phase transformation and capacity fading. Here, it is shown that surface doping of vanadium (V5+) cations into LLC material suppresses both the irreversible oxygen release and undesirable phase transformation, resulting in the improvement of capacity retention. The V‐doped LLC shows a high discharge capacity of 244.3 ± 0.8 mAh g−1 with 92% retention after 100 cycles, whereas LLC delivers 233.6 ± 1.1 mAh g−1 with 74% retention. Furthermore, the average discharge voltage of V‐doped LLC drops by only 0.33 V after 100 cycles, while LLC exhibits 0.43 V of average discharge voltage drop. Experimental and theoretical investigations indicate that doped V‐doping increase the transition metal–oxygen (TMO) covalency and affect the oxidation state of peroxo‐like (O2)n− species during the delithiation process. The role of V‐doping to make the oxygen redox reversible in LLC materials for high‐energy density Li‐ion batteries is illustrated here.
Precision Surface Microtopography Regulates Cell Fate via Changes to Actomyosin Contractility and Nuclear Architecture
Authors: Carthew James , Abdelmaksoud Hazem H. , Hodgson‐Garms Margeaux , Aslanoglou Stella , Ghavamian Sara , Elnathan Roey , Spatz Joachim P. , Brugger Juergen , Thissen Helmut , Voelcker Nicolas H. , Cadarso Victor J. , Frith Jessica E.
Published: January 2021

Cells are able to perceive complex mechanical cues from their microenvironment, which in turn influences their development. Although the understanding of these intricate mechanotransductive signals is evolving, the precise roles of substrate microtopography in directing cell fate is still poorly understood. Here, UV nanoimprint lithography is used to generate micropillar arrays ranging from 1 to 10 µm in height, width, and spacing to investigate the impact of microtopography on mechanotransduction. Using mesenchymal stem cells (MSCs) as a model, stark pattern‐specific changes in nuclear architecture, lamin A/C accumulation, chromatin positioning, and DNA methyltransferase expression, are demonstrated. MSC osteogenesis is also enhanced specifically on micropillars with 5 µm width/spacing and 5 µm height. Intriguingly, the highest degree of osteogenesis correlates with patterns that stimulated maximal nuclear deformation which is shown to be dependent on myosin‐II‐generated tension. The outcomes determine new insights into nuclear mechanotransduction by demonstrating that force transmission across the nuclear envelope can be modulated by substrate topography, and that this can alter chromatin organisation and impact upon cell fate. These findings have potential to inform the development of microstructured cell culture substrates that can direct cell mechanotransduction and fate for therapeutic applications in both research and clinical sectors.
Cytosolic Delivery of Thiolated Neoantigen Nano‐Vaccine Combined with Immune Checkpoint Blockade to Boost Anti‐Cancer T Cell Immunity
Authors: Zhang Da , Lin Ziguo , Wu Ming , Cai Zhixiong , Zheng Youshi , He Lei , Li Zhenli , Zhou Jie , Sun Liqin , Chen Geng , Zeng Yongyi , Li Juan , Liu Jingfeng , Yang Huanghao , Liu Xiaolong
Published: January 2021

Although tumor‐specific neoantigen‐based cancer vaccines hold tremendous potential, it still faces low cross‐presentation associated with severe degradation via endocytosis pathway. Herein, a thiolated nano‐vaccine allowing direct cytosolic delivery of neoantigen and Toll like receptor 9 agonist CpG‐ODN is developed. This approach is capable of bypassing the endo‐/lysosome degradation, increasing uptake and local concentration of neoantigen and CpG‐ODN to activate antigen‐presenting cells, significantly strengthening the anti‐cancer T‐cell immunity. In vivo immunization with thiolated nano‐vaccine enhanced the lymph organ homing and promoted the antigen presentation on dendritic cells, effectively inhibited tumor growth, and significantly prolonged the survival of H22‐bearing mice. Strikingly, further combination of the thiolated nano‐vaccine with anti‐programmed cell death protein‐1 antibody (αPD‐1) could efficiently reverse immunosuppression and enhance response rate of tumors, which led to enhanced tumor elimination, complete prevention of tumor re‐challenge, and long‐term survival above 150 d. Collectively, a versatile methodology to design cancer vaccines for strengthening anti‐cancer T‐cell immunity in solid tumors is presented, which could be further remarkably enhanced by combining with immune checkpoint inhibitors.
Recent Advances in GaN‐Based Power HEMT Devices
Authors: He Jiaqi , Cheng Wei‐Chih , Wang Qing , Cheng Kai , Yu Hongyu , Chai Yang
Published: January 2021

The ever‐increasing power density and operation frequency in electrical power conversion systems require the development of power devices that can outperform conventional Si‐based devices. Gallium nitride (GaN) has been regarded as the candidate for next‐generation power devices to improve the conversion efficiency in high‐power electric systems. GaN‐based high electron mobility transistors (HEMTs) with normally‐off operation is an important device structure for different application scenarios. In this review, an overview of a series of effective approaches to improve the performance of GaN‐based power HEMT devices is given. Modified epistructures are presented to suppress defects and current leakage, and low‐damage recess‐free processes are discussed in fabricating normally‐off HEMTs. Possible effects of dielectrics on a metal–insulator–semiconductor (MIS) structure are also intensively introduced. Metal/semiconductor contact engineering is investigated, and fabrication of Au‐free ohmic contact and graphene insertion layer to enhance the device performance is emphasized. Finally, the effects of field plates are studied through the use of simulated and fabricated devices.
Metal‐Free Organic Halide Perovskite: A New Class for Next Optoelectronic Generation Devices
Authors: Song Xin , Hodes Gary , Zhao Kui , Liu Shengzhong (Frank)
Published: January 2021

Even though the metal‐halide perovskites are attracting ever‐increasing interest for their breakthrough efficiencies in photovoltaics, light‐emitting diodes (LED), X‐ray imaging, and general optoelectronics, it was not until very recently that metal‐free halide perovskites become recognized, not only for their good optoelectronic performance, but also for their wide chemical diversity, tunability, lightweight, mechanical flexibility, and eco‐friendly processability. The community is turning their attention to these lightweight semiconductors, and promising results have been achieved in the initial evaluation of crystal structure and a range of properties including ferroelectric and optoelectronic properties. In this review, the crystal structure and synthesis of these materials are discussed together with the various properties that have been studied for these materials. Future prospects are further discussed for chemical diversity, structure tunability, synthetic process, potential properties, optoelectronic, and energy‐related applications.
Historical trends of residential water use in California: Effects of droughts and conservation policies
Authors: Lee Juhee , Nemati Mehdi , Dinar Ariel
Published: January 2021

Conservation efforts to reduce residential water use have a long history in California. This article examines residential water use changes, measured by gallons per capita per day (GPCD), using a comprehensive monthly panel dataset of California's public water agencies during 1994–2019. We find that, on average, GPCD was reduced by 34% in 2019 when compared to 1994 levels. Controlling for the region, water source, and water agency characteristics suggest significant differences in policy performance. The differential effectiveness of conservation policies indicates a need to consider policy differentiation based on the agencies' objective and subjective conditions.
Single‐Molecule Counting Coupled to Rapid Amplification Enables Detection of α‐Synuclein Aggregates in Cerebrospinal Fluid of Parkinson's Disease Patients
Authors: Bhumkar Akshay , Magnan Chloe , Lau Derrick , Jun Eugene Soh Wei , Dzamko Nicolas , Gambin Yann , Sierecki Emma
Published: January 2021

α‐Synuclein aggregation is a hallmark of Parkinson's disease and a promising biomarker for early detection and assessment of disease progression. The prospect of a molecular test for Parkinson's disease is materializing with the recent developments of detection methods based on amplification of synuclein seeds (e.g. RT‐QuIC or PMCA). Here we adapted single‐molecule counting methods for the detection of α‐synuclein aggregates in cerebrospinal fluid (CSF), using a simple 3D printed microscope. Single‐molecule methods enable to probe the early events in the amplification process used in RT‐QuIC and a precise counting of ThT‐positive aggregates. Importantly, the use of single‐molecule counting also allows a refined characterization of the samples and fingerprinting of the protein aggregates present in CSF of patients. The fingerprinting of size and reactivity of individual aggregate shows a unique signature for each PD patients compared to controls and may provide new insights on synucleinopathies in the future.
Metal Sub‐nanoclusters Confined within Hierarchical Porous Carbons with High Oxidation Activity
Authors: Zhao Xin , Kong Xiangpeng , Wang Fengliang , Fang Ruiqi , Li Yingwei
Published: January 2021

Metal sub‐nanoclusters (SNCs) have shown great promise for a variety of catalytic reactions. However, the fabrication of stable metal SNCs simultaneously with high dispersion and high metal contents remains a challenge. Herein, we report a novel and versatile strategy for the synthesis of various bimetal SNCs stabilized within hierarchical porous carbons (HPC). This facile synthesis only involves the self‐assembly of a metal‐organic framework (MOF) as the precursor, a molten salt assisted pyrolysis process and the final metal replacement. The metal SNCs (mostly less than 0.8 nm) derived from the metal nodes of the MOF are exclusively confined and homogeneously dispersed throughout the organic ligands derived HPC at high loadings (up to 11.2 wt %). The obtained Cu‐Pd@HPC composite exhibits superior catalytic activity and recycling durability in the selective transformation of furfural to maleic acid, achieving 97.8 % yield of maleic acid with a TOF value as high as 20.1 h−1 under mild conditions. DFT calculations reveal that the introduction of Pd shifts the partial density of states of Cu toward the Fermi level, leading to stronger chemisorption of furfural to enhance the catalytic activity.
Stepped Channels Integrated Lithium–Sulfur Separator via Photoinduced Multidimensional Fabrication of Metal–Organic Frameworks
Authors: Gao Guang‐Kuo , Wang Yi‐Rong , Wang Si‐Bo , Yang Ru‐Xin , Chen Yifa , Zhang Yu , Jiang Cheng , Wei Mei‐Jie , Ma Huiyuan , Lan Ya‐Qian
Published: January 2021

Multidimensional fabrication of metal–organic frameworks (MOFs) into multilevel channel integrated devices are in high demanded for Li‐S separators. Such separators have advantages in pore‐engineering that might fulfill requirements such as intercepting the diffusing polysulfides and improving the Li+/electrolyte transfer in Li‐S batteries. However, most reported works focus on the roles of MOFs as ionic sieves for polysulfides while offering limited investigation on the tuning of Li+ transfer across the separators. A photoinduced heat‐assisted processing strategy is proposed to fabricate MOFs into multidimensional devices (e.g., hollow/Janus fibers, double‐or triple‐layer membranes). For the first time, a triple‐layer separator with stepped‐channels has been designed and demonstrated as a powerful separator with outstanding specific capacity (1365.0 mAh g−1) and cycling performance (0.03 % fading per cycle from 100th to 700th cycle), which is superior to single/double‐layer and commercial separators. The findings may expedite the development of MOF‐based membranes and extend the scope of MOFs in energy‐storage technologies.
A TADF Emitter Featuring Linearly Arranged Spiro‐Donor and Spiro‐Acceptor Groups: Efficient Nondoped and Doped Deep‐Blue OLEDs with CIEy<0.1
Authors: Xia Guoqi , Qu Cheng , Zhu Yunlong , Ye Jianjiang , Ye Kaiqi , Zhang Zuolun , Wang Yue
Published: January 2021

Reported herein is a molecular design strategy of deep‐blue emitters for resolving the lack of highly efficient deep‐blue organic light‐emitting diodes (OLEDs) featuring CIEy(Commission Internationale de l'Eclairage) color coordinates matching the display requirements (<0.1). The strategy is to combine weak spiro‐donor and spiro‐acceptor groups into a linear donor‐π‐acceptor type of thermally‐activated delayed fluorescence molecule through a sterically bulky π‐spacer. The strategy endows an emitter with deep‐blue emission, a narrower emission bandwidth (51 nm in toluene), a high photoluminescence quantum yield (0.95 in toluene), weak concentration quenching, and efficient triplet‐exciton utilization, which are all attractive characteristics for emitters of deep‐blue OLEDs with lower CIEycoordinates. Owing to the rational design, the emitter has realized not only highly efficient doped deep‐blue OLEDs with external quantum efficiencies (EQEs) up to 25.4 % and CIEyless than 0.1 but also so far the most efficient nondoped deep‐blue OLED (EQE up to 22.5 %) with CIEyless than 0.1.
Deciphering the Supramolecular Organization of Multiple Guests Inside a Microporous MOF to Understand their Release Profile
Authors: Balestri Davide , Mazzeo Paolo P. , Perrone Roberto , Fornari Fabio , Bianchi Federica , Careri Maria , Bacchi Alessia , Pelagatti Paolo
Published: January 2021

Metal‐organic frameworks (MOFs) give the opportunity of confining guest molecules into their pores even by a post‐synthetic protocol. PUM168 is a Zn‐based MOF characterized by microporous cavities that allows the encapsulation of a significant number of guest molecules. The pores engineered with different binding sites show a remarkable guest affinity towards a series of natural essential oils components, such as eugenol, thymol and carvacrol, relevant for environmental applications. Exploiting single crystal X‐ray diffraction, it was possible to step‐wisely monitor the rather complex three‐components guest exchange process involving dimethylformamide (DMF, the pristine solvent) and binary mixtures of the flavoring agents. A picture of the structural evolution of the DMF‐to‐guest replacement occurring inside the MOF crystal was reached by a detailed single‐crystal‐to‐single‐crystal monitoring. The relation of the supramolecular arrangement in the pores with selective guests release was then investigated as a function of time and temperature by static headspace GC‐MS analysis.
Genomic and transcriptomic resources for candidate gene discovery in the Ranunculids
Authors: Arias Tatiana , Riaño‐Pachón Diego Mauricio , Di Stilio Verónica S.
Published: January 2021

Premise

Multiple transitions from insect to wind pollination are associated with polyploidy and unisexual flowers in Thalictrum (Ranunculaceae), yet the underlying genetics remains unknown. We generated a draft genome of Thalictrum thalictroides, a representative of a clade with ancestral floral traits (diploid, hermaphrodite, and insect pollinated) and a model for functional studies. Floral transcriptomes of T. thalictroides and of wind‐pollinated, andromonoecious T. hernandezii are presented as a resource to facilitate candidate gene discovery in flowers with different sexual and pollination systems.

Methods

A draft genome of T. thalictroides and two floral transcriptomes of T. thalictroides and T. hernandezii were obtained from HiSeq 2000 Illumina sequencing and de novo assembly.

Results

The T. thalictroides de novo draft genome assembly consisted of 44,860 contigs (N50 = 12,761 bp, 243 Mbp total length) and contained 84.5% conserved embryophyte single‐copy genes. Floral transcriptomes contained representatives of most eukaryotic core genes, and most of their genes formed orthogroups.

Discussion

To validate the utility of these resources, potential candidate genes were identified for the different floral morphologies using stepwise data set comparisons. Single‐copy gene analysis and simple sequence repeat markers were also generated as a resource for population‐level and phylogenetic studies.
Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer's disease
Authors: Shukur Karar T. , Ercetin Tugba , Luise Chiara , Sippl Wolfgang , Sirkecioglu Okan , Ulgen Mert , Coskun Goknil P. , Yarim Mine , Gazi Mustafa , Gulcan Hayrettin O.
Published: January 2021

A series of urolithin amide (i.e., URO‐4–URO‐10 and THU‐4–THU‐10) derivatives was designed and synthesized, and their chemical structures were confirmed with spectroscopic techniques and elemental analysis. The title compounds and synthesis intermediates (THU‐1–THU‐10 and URO‐1–URO‐10) were evaluated for their potential to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO‐B). Compounds THU‐4 and THU‐8 were found to be the most potent inhibitors for the cholinesterases and MAO‐B, respectively. The docking studies were also employed to evaluate the binding modes of the most active compounds with AChE, BuChE, and MAO‐B. Furthermore, the moderate‐to‐strong activities of the compounds were also displayed in amyloid‐beta inhibition and antioxidant assay systems. The results pointed out that the urolithin scaffold can be employed in drug design studies for the development of multitarget ligands acting on various cascades shown to be important within the pathophysiology of Alzheimer's disease.
The objects in observations of Perseus cluster region
Authors: Sinitsyna Vera G. , Sinitsyna Vera Yu.
Published: January 2021

The results of 20‐year observations of the Perseus cluster centering on the NGC 1275 including IC 310 radio galaxy and extragalactic supernova SN 2006gy at energies 800 GeV to 45 TeV by the SHALON telescope are presented. Also, the emission from the galactic source of non‐thermal radio and X‐ray emission GK Per (Nova 1901) of classical nova type was found as it accompanied to the observations. For NGC 1275, it was found that the TeV γ‐ray emission at energies >800 GeV has an extended structure with a distinct core centered at the NGC 1275 nucleus and well correlates with the photon emission regions viewed in X‐rays by Chandra and anti‐correlates with radio‐structures. Also, the variations of TeV γ‐ray flux both at year‐ and day scales were found. The obtained data indicate that the part of TeV γ‐ray emission is generated by relativistic jets in the nucleus of NGC 1275. Whereas the presence of an extended structure around NGC 1275 and the slow rise of the γ‐ray flux is the evidence of the interaction of cosmic rays and magnetic fields generated in the jets at the galactic center with the gas of the Perseus cluster.
Comparing outcomes of general anesthesia and monitored anesthesia care during transcatheter aortic valve replacement: The Cleveland Clinic Foundation experience
Authors: Sammour Yasser , Kerrigan Jimmy , Banerjee Kinjal , Gajulapalli Rama Dilip , Lak Hassan , Chawla Sanchit , Andress Krystof , Gupta Neha , Unai Shinya , Svensson Lars G. , Yun James , Reed Grant W , Alfirevic Andrej , Sale Shiva , Mehta Anand , Krishnaswamy Amar , Skubas Nikolaos , Kapadia Samir
Published: January 2021

Background

Monitored anesthesia care (MAC) has become more widely used during transcatheter aortic valve replacement (TAVR) to avoid the complications of general anesthesia (GA).

Methods

We included consecutive patients who underwent transfemoral‐TAVR at our institution between January 2012 and April 2017. We compared outcomes with GA versus MAC.

Results

Of 998 patients, MAC was used in 43.9%. MAC was associated with shorter procedural time (96.9 ± 30.9 vs. 135 ± 64.6 mins; p < .001), fluoroscopy time (20.4 ± 8.9 vs. 29 ± 18.7 mins; p < .001), lower contrast volume (45.5 ± 27 vs. 60.4 ± 43 cc; p < .001), and decreased radiation exposure (12,869 ± 8,099 vs. 20,630 ± 16,276 cGy‐cm2; p < .001). Patients who underwent MAC had a briefer median (IQR) intensive care unit stay [23.3 (21–24) vs. 23.4 (20.8–26) hrs; p < .001], and hospital stay [2 (2, 3) vs. 3 (2–6) days; p < .001], and were more frequently discharged to home (93.4% vs. 82.9%; p < .001). MAC was associated with lower mortality at 30 days (0.5% vs. 2.9%; log‐rank p = .012; adjHR 0.22, 95% CI 0.06–0.82; p = .024), but not at 1 year (11.7% vs. 14.6%; log‐rank p = .157) or 3 years (36.8% vs. 38.4%; log‐rank p = 0.433). There were no differences in major adverse cardiac and cerebrovascular events (MACCE) at either 30 days (4.6% vs. 9.3%; log‐rank p = .14) or 1 year (21.1% vs. 21.5%; log‐rank p = .653). Similar findings were seen among patients who received newer‐generation SAPIEN‐3 valves.

Conclusion

Utilizing MAC and omitting intraprocedural transesophageal echocardiography during TAVR seems to be more efficient without compromising safety. Better TAVR outcomes can be achieved with newer generation valves without needing GA.
Huge carbuncle leading to necrotizing fasciitis in the COVID‐19 pandemic era
Authors: Gheisari Mehdi , Baghani Moein , Ganji Raziyeh , Forouzanfar Mohammad‐Mehdi
Published: January 2021

Although Necrotizing fasciitis can evolve from a trivial lesion, whenever it develops it requires a prompt surgical intervention and broad‐spectrum antibiotic therapy.
Titanium Complexes with Functional Alkoxido Ligands for Selective Ethylene Dimerization – A High Throughput Experimentation Approach
Authors: Grasset Fabien L. , Welter Richard , Braunstein Pierre , Olivier‐Bourbigou Hélène , Magna Lionel
Published: January 2021

New titanium complexes of general formula [Ti(OR)2(OiPr)2], containing functionalized alkoxido ligands, were developed for the selective catalytic dimerization of ethylene to 1‐butene using a combined High Throughput Screening (HTS) / Design of Experiment (DoE) approach. First, a library of 19 ligands was elaborated and a primary screening spotted the phosphorus‐functionalized alkoxido ligands as most promising. A second, more focused library containing 8 alkoxidophosphane ligands was then developed. A longer linear spacer between the alkoxido and the phosphorus functions, as in [Ti(19)2(OiPr)2], was found beneficial for this catalytic reaction. After identification of the best co‐catalyst (AlEt3) and co‐ligand (OnBu), final optimization of the reaction conditions was performed using a design of experiments (DoE) approach. The complex [Ti(19)2(OnBu)2] was shown to selectively dimerize ethylene in 1‐butene (C4(α)=93 % (99+%)) at 30 bar C2H4 and 55 °C with AlEt3 as co‐catalyst, resulting in very high activity and selectivity for a molecular titanium catalyst (13000 g gTi−1 h−1, 93 % 1‐butene).