bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of the sonic hedgehog pathway activates TGF-β-activated kinase (TAK1) to induce autophagy and suppress apoptosis in thyroid tumor cells
Authors: Li Sumei , Wang Jingxiang , Lu Yurong , Zhao Yuqing , Prinz Richard A. , Xu Xiulong
Published: May 2021

The sonic hedgehog (Shh) pathway is highly activated in a variety of malignancies and plays important roles in tumorigenesis, tumor growth, drug resistance, and metastasis. Our recent study showed that the inhibitors of the Shh pathway such as cyclopamine (CP), a Smothened (SMO) inhibitor, and GANT61, a Gli1 inhibitor, have modest inhibitory effects on thyroid tumor cell proliferation and tumor growth. The objective of this study was to determine whether autophagy was induced by inhibition of the Shh pathway and could negatively regulate GANT61-induced apoptosis. Here we report that inhibition of the Shh pathway by Gli1 siRNA or by cyclopamine and GANT61 induced autophagy in SW1736 and KAT-18 cells, two anaplastic thyroid cancer cell lines; whereas Gli1 overexpression suppressed autophagy. Mechanistic investigation revealed that inhibition of the Shh pathway activated TAK1 and its two downstream kinases, the c-Jun-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). GANT61-induced autophagy was blocked by TAK1 siRNA and the inhibitors of TAK1 (5Z-7-oxozeaenol, 5Z), JNK (SP600125), and AMPK (Compound C, CC). Inhibition of autophagy by chloroquine and 5Z and by TAK1 and Beclin-1 siRNA enhanced GANT61-induced apoptosis and its antiproliferative activity. Our study has shown that inhibition of the Shh pathway induces autophagy by activating TAK1, whereas autophagy in turn suppresses GANT61-induced apoptosis. We have uncovered a previously unrecognized role of TAK1 in Shh pathway inhibition-induced autophagy and apoptosis.
DNAJB9 suppresses the metastasis of triple-negative breast cancer by promoting FBXO45-mediated degradation of ZEB1
Authors: Kim Hye-Youn , Kim Young-Mi , Hong Suntaek
Published: May 2021

DNAJB9, a member of the heat shock protein 40 family, acts as a multifunctional player involved in the maintenance of their client proteins and cellular homeostasis. However, the mechanistic action of DNAJB9 in human malignancies is yet to be fully understood. In this study, we found that ectopic restoration of DNAJB9 inhibits the migration, invasion, in vivo metastasis, and lung colonization of triple-negative breast cancer (TNBC) cells. Mechanistically, DNAJB9 stabilizes FBXO45 protein by suppressing self-ubiquitination and reduces the abundance of ZEB1 by Lys48-linked polyubiquitination to inhibit the epithelial–mesenchymal transition (EMT) and metastasis. Clinically, the reduction of DNAJB9 expression, concomitant with decreased FBXO45 abundance in breast cancer tissues, correlates with poorer clinical outcomes of patients with breast cancer. Taken together, our results provide a novel insight into the metastasis of TNBC and define a promising therapeutic strategy for cancers with overactive ZEB1 by regulating the DNAJB9–FBXO45 signaling axis.
Silencing TAK1 reduces MAPKs-MMP2/9 expression to reduce inflammation-driven neurohistological disruption post spinal cord injury
Authors: Jiang Shuai , Wu Yandan , Wu Shunjie , Ye Suhui , Kong Renyi , Chang Jie , Xia Mingjie , Bao Junping , Peng Xin , Hong Xin , Qian Zhanyang , Li Haijun
Published: May 2021

Microglia activation post traumatic spinal cord injury (SCI) provokes accumulation of inflammatory metabolites, leading to increasing neurological disruption. Our previous studies demonstrated that blocking MAPKs pathway mitigated microglia inflammatory activation and prevented cords from neuroinflammation-induced secondary injury. Transforming growth factor-β-activated kinase 1 (TAK1) is an upstream gate regulating activation of MAPKs signaling. To validate the therapeutic effect of TAK1 inhibition in neuroinflammation post SCI, in the current study, cultures of microglia BV2 line was undergone lipopolysaccharide (LPS) stimulation in the presence of TAK1 inhibitor 5Z-7-Oxozeaenol (ZO), LPS, or control. LPS triggered inflammatory level, cell migration, and matrix metalloproteinase (MMP) 2/9 production, which was reduced in ZO-treated cultures. TAK1 inhibition by ZO also decreased activation of MAPKs pathway, indicating that ZO-mediated alleviation of neuroinflammation is likely modulated via TAK1/MAPKs axis. In vivo, neuroinflammatory level and tissue destruction were assessed in adult male mice that were undergone SCI by mechanical trauma, and treated with ZO by intraperitoneal injection. Compared with SCI mice, ZO-treated mice exhibited less microglia pro-inflammatory activation and accumulation adjacent to injured core linked to reduced MMP2/9 expression, leading to minor tissue damage and better locomotor recovery. To sum up, the obtained data proved that in the early phase post SCI, TAK1 inhibition impedes microglia biological activities including activation, enzymatic synthesis, and migration via downregulation of MAPKs pathway, and the effects may be accurately characterized as potent anti-inflammation.
Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week
Authors: Hu Yawei , Sui Xizhao , Song Fan , Li Yaqian , Li Kaiyi , Chen Zhongyao , Yang Fan , Chen Xiuyuan , Zhang Yaohua , Wang Xianning , Liu Qiang , Li Cong , Zou Binbin , Chen Xiaofang , Wang Jun , Liu Peng
Published: May 2021

While the potential of patient-derived organoids (PDOs) to predict patients’ responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.
Odd Willis coupling induced by broken time-reversal symmetry
Authors: Quan Li , Yves Simon , Peng Yugui , Esfahlani Hussein , Alù Andrea
Published: May 2021

When sound interacts with geometrically asymmetric structures, it experiences coupling between pressure and particle velocity, known as Willis coupling. While in most instances this phenomenon is perturbative in nature, tailored asymmetries combined with resonances can largely enhance it, enabling exotic acoustic phenomena. In these systems, Willis coupling obeys reciprocity, imposing an even symmetry of the Willis coefficients with respect to time reversal and the impinging wave vector, which translates into stringent constraints on the overall scattering response. In this work, we introduce and experimentally observe a dual form of acoustic Willis coupling, arising in geometrically symmetric structures when time-reversal symmetry is broken, for which the pressure-velocity coupling is purely odd-symmetric. We derive the conditions to maximize this effect, we experimentally verify it in a symmetric subwavelength scatterer biased by angular momentum, and we demonstrate the opportunities for sound scattering enabled by odd Willis coupling. Our study opens directions for acoustic metamaterials, with direct implications for sound control, non-reciprocal scattering, wavefront shaping and signal routing, of broad interest also for nano-optics, photonics, elasto-dynamics, and mechanics.
Deep learning-based predictive identification of neural stem cell differentiation
Authors: Zhu Yanjing , Huang Ruiqi , Wu Zhourui , Song Simin , Cheng Liming , Zhu Rongrong
Published: May 2021

The differentiation of neural stem cells (NSCs) into neurons is proposed to be critical in devising potential cell-based therapeutic strategies for central nervous system (CNS) diseases, however, the determination and prediction of differentiation is complex and not yet clearly established, especially at the early stage. We hypothesize that deep learning could extract minutiae from large-scale datasets, and present a deep neural network model for predictable reliable identification of NSCs fate. Remarkably, using only bright field images without artificial labelling, our model is surprisingly effective at identifying the differentiated cell types, even as early as 1 day of culture. Moreover, our approach showcases superior precision and robustness in designed independent test scenarios involving various inducers, including neurotrophins, hormones, small molecule compounds and even nanoparticles, suggesting excellent generalizability and applicability. We anticipate that our accurate and robust deep learning-based platform for NSCs differentiation identification will accelerate the progress of NSCs applications.
Inner hair cell stereocilia are embedded in the tectorial membrane
Authors: Hakizimana Pierre , Fridberger Anders
Published: May 2021

Mammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.
Author Correction: Strongly confined localized surface plasmon resonance (LSPR) bands of Pt, AgPt, AgAuPt nanoparticles
Authors: Sui Mao , Kunwar Sundar , Pandey Puran , Lee Jihoon
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Allopurinol ameliorates high fructose diet induced hepatic steatosis in diabetic rats through modulation of lipid metabolism, inflammation, and ER stress pathway
Authors: Cho In-Jin , Oh Da-Hee , Yoo Jin , Hwang You-Cheol , Ahn Kyu Jeung , Chung Ho-Yeon , Jeong Soung Won , Moon Ju-Young , Lee Sang-Ho , Lim Sung-Jig , Jeong In-Kyung
Published: May 2021

Excess fructose consumption contributes to development obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). Uric acid (UA), a metabolite of fructose metabolism, may have a direct role in development of NAFLD, with unclear mechanism. This study aimed to evaluate role of fructose and UA in NAFLD and explore mechanisms of allopurinol (Allo, a UA lowering medication) on NAFLD in Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed a high fructose diet (HFrD), with Long-Evans Tokushima Otsuka (LETO) rats used as a control. There were six groups: LETO, LETO-Allo, OLETF, OLETF-Allo, OLETF-HFrD, and OLETF-HFrD-Allo. HFrD significantly increased body weight, epididymal fat weight, and serum concentrations of UA, cholesterol, triglyceride, HbA1c, hepatic enzymes, HOMA-IR, fasting insulin, and two hour-glucose after intraperitoneal glucose tolerance tests, as well as NAFLD activity score of liver, compared to the OLETF group. Allopurinol treatment significantly reduced hepatic steatosis, epididymal fat, serum UA, HOMA-IR, hepatic enzyme levels, and cholesterol in the OLETF-HFrD-Allo group. Additionally, allopurinol significantly downregulated expression of lipogenic genes, upregulated lipid oxidation genes, downregulated hepatic pro-inflammatory cytokine genes, and decreased ER-stress induced protein expression, in comparison with the OLETF-HFrD group. In conclusion, allopurinol ameliorates HFrD-induced hepatic steatosis through modulation of hepatic lipid metabolism, inflammation, and ER stress pathway. UA may have a direct role in development of fructose-induced hepatic steatosis, and allopurinol could be a candidate for prevention or treatment of NAFLD.
Figla promotes secondary follicle growth in mature mice
Authors: Okunomiya Asuka , Horie Akihito , Tani Hirohiko , Sato Yukiyasu , Takamatsu Shiro , Brown J. B. , Sugimoto Miki , Hamanishi Junzo , Kondoh Eiji , Matsumura Noriomi , Mandai Masaki
Published: May 2021

The in vitro growth (IVG) of human follicles is a potential fertility option for women for whom cryopreserved ovarian tissues cannot be transplanted due to the risk of cancer cell reintroduction; however, there is currently no established method. Furthermore, optimal IVG conditions may differ between the follicles of adult and pre-pubertal females due to molecular differences suggested by basic research. To systematically identify differences between the secondary follicles of adult and pre-pubertal females, a comparative transcriptomic study using mice was conducted herein. Among differentially expressed genes (DEGs), Figla was up-regulated in mature mice. We successfully down-regulated Figla expression in secondary follicle oocytes by a Figla siRNA microinjection, and the subsequent IVG of follicles showed that the diameter of these follicles was smaller than those of controls in mature mice, whereas no significant difference was observed in premature mice. The canonical pathways of DEGs between control and Figla-reduced secondary follicles suggest that Figla up-regulates VDR/RXR activation and down-regulates stem cell pluripotency as well as estrogen signaling. We demonstrated for the first time that folliculogenesis of the secondary follicles of premature and mature mice may be regulated by different factors, such as Figla with its possible target genes, providing insights into optimal IVG conditions for adult and pre-pubertal females, respectively.
Effect of citric-acid dialysate on the QTC-interval
Authors: ter Meulen Karlien J. , Hermans Ben J. M. , van der Sande Frank M. , Canaud Bernard , Konings Constantijn J. A. M. , Kooman Jeroen P. , Delhaas Tammo
Published: May 2021

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p < 0.001), but not with A1.5 (from 439 to 443 ms; p = 0.13). In conclusion, we found that the use of C1.5 or A1.25 is associated with a significant prolongation of QTc which was however relatively limited.
Prevalence of STIs, sexual practices and substance use among 2083 sexually active unmarried women in Lebanon
Authors: Zaki Sara Abu , Naous Jihane , Ghanem Antoine , Abou Abbas Diana , Tomb Roland , Ghosn Jade , Assi Ayman
Published: May 2021

Access to sexual and reproductive health in conservative communities and in the MENA region are particularly limited and, as such, increase women’s vulnerability to unwanted pregnancies, unsafe abortions, and sexually transmitted infections (STIs). The aim was to assess the prevalence of STIs, sexual practices, recreational drug-use and their possible associations among cisgender unmarried women residing in Lebanon. Data on demographics, sexual practices and substance-use were collected from 2083 unmarried cisgender women who voluntarily attended a sexual health clinic in Lebanon between 2015 and 2019. They tested for HIV, Hepatitis B, Hepatitis C and Syphilis through rapid testing. Other infections (genital warts, Neisseria gonorrhea/Chlamydia trachomatis) were screened for. Regression models were computed between variables. There were two cases of HIV, one of Hepatitis B and syphilis, and no cases of Hepatitis C. Genital warts were present in 15% and symptoms indicative of Neisseria gonorrhea/Chlamydia trachomatis in 14%. Inconsistent condom-use (81%) was significantly associated with number of partners (adj. OR: 0.4). Inconsistent condom-use discussion with partners (33%) was significantly associated with unemployment (adj OR: 1.7), recreational drug-use (adj. OR: 1.4), and number of partners (adj. ORs 3.7–4.4). Unwanted pregnancies (11%) were significantly associated with age (adj. ORs 0.1–0.37), recreational drug-use (adj. OR: 2), using intrauterine device (adj. OR:2.9) and natural birth control methods (adj. OR: 2.4). Recreational drug-use (33%) was significantly associated with age (adj ORs 1.9–2.2), and smoking status (adj. OR: 0.6). The results indicate an urgent need for: (1) Accessible, non-stigmatizing, and inclusive sexual health services dedicated to women’s sexual health; (2) Comprehensive and non-stigmatizing sexual health education for all, but especially women, in order to promote safer sexual practices and effective decision making with regards to contraception and condom-use.
Psychosis risk individuals show poor fitness and discrepancies with objective and subjective measures
Authors: Damme Katherine S. F. , Sloan Richard P. , Bartels Matthew N. , Ozsan Alara , Ospina Luz H. , Kimhy David , Mittal Vijay A.
Published: May 2021

Exercise is a promising intervention for individuals at clinical high-risk for psychosis (CHR). However, these youth may not be reliable reporters on fitness. There have been no investigations that utilized objective fitness assessment in this population. The present study objectively characterizes the level of fitness in CHR youth, compares the accuracy of self-report measures to objective fitness indices, and explores clinical factors that may influence the accuracy of self-reported measures of fitness. Forty CHR individuals completed an exercise survey and objective indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed objective indices of fitness and a structured clinical interview ruling out the presence of psychiatric illness. CHR youth showed greater BMI and lowered VO2max compared to healthy volunteers. In the CHR group, self-report items (perceived fitness) did not reflect objective indices of fitness, whereas specific exercise behaviors (intensity of exercise) showed stronger correlations with objective fitness measurements. Exploratory analyses suggested that symptoms (grandiosity and avolition) related to errors in self-perception. Results indicate that CHR individuals are less fit than controls as indexed by objective measures of fitness and that it is important to consider unique population clinical characteristics when employing self-report data.
Development of a Loop-mediated isothermal amplification (LAMP) technique for specific and early detection of Mycobacterium leprae in clinical samples
Authors: Garg Nupur , Sahu Upasana , Kar Sudeshna , Ahmad Farhan J.
Published: May 2021

Leprosy, a progressive, mutilating and highly stigmatized disease caused by Mycobacterium leprae (ML), continues to prevail in the developing world. This is due to the absence of rapid, specific and sensitive diagnostic tools for its early detection since the disease gets notified only with the advent of physical scarring in patients. This study reports the development of a Loop-mediated isothermal amplification (LAMP) technique for fast, sensitive and specific amplification of 16S rRNA gene of ML DNA for early detection of leprosy in resource-limited areas. Various parameters were optimized to obtain robust and reliable amplification of ML DNA. Blind clinical validation studies were performed which showed that this technique had complete concurrence with conventional techniques. Total absence of amplification of negative control DNA confirmed the specificity of this test. Various visual detection methods viz. colorimetric, turbidity differentiation and bridge flocculation were standardized to establish easy-to-read and rapid diagnosis. This technique eliminates the lack of accuracy and sensitivity in skin smear tests in patients and the requirement for expensive lab equipments and trained technicians. The technique holds promise for further expansion and has the potential to cater to the unmet needs of society for a cheap, highly-sensitive and robust rapid diagnosis of ML.
Bilayer and three dimensional conductive network composed by SnCl2 reduced rGO with CNTs and GO applied in transparent conductive films
Authors: Tian Ying , Guo Ning , Wang Wen-Yi , Geng Wenming , Jing Li-Chao , Wang Tao , Yuan Xiao-Tong , Zhu Zeru , Ma Yicheng , Geng Hong-Zhang
Published: May 2021

Graphene oxide (GO), reduced graphene oxide (rGO) and carbon nanotubes (CNTs) have their own advantages in electrical, optical, thermal and mechanical properties. An effective combination of these materials is ideal for preparing transparent conductive films to replace the traditional indium tin oxide films. At present, the preparation conditions of rGO are usually harsh and some of them have toxic effects. In this paper, an SnCl2/ethanol solution was selected as the reductant because it requires mild reaction conditions and no harmful products are produced. The whole process of rGO preparation was convenient, fast and environmentally friendly. Then, SEM, XPS, Raman, and XRD were used to verify the high reduction efficiency. CNTs were introduced to improve the film conductive property. The transmittance and sheet resistance were the criteria used to choose the reduction time and the content ratios of GO/CNT. Thanks to the post-treatment of nitric acid, not only the by-product (SnO2) and dispersant in the film are removed, but also the doping effect occurs, which are all conducive to reducing the sheet resistances of films. Ultimately, by combining rGO, GO and CNTs, transparent conductive films with a bilayer and three-dimensional structure were prepared, and they exhibited high transmittance and low sheet resistance (58.8 Ω/sq. at 83.45 T%, 47.5 Ω/sq. at 79.07 T%), with corresponding $${{\sigma_{dc} } \mathord{\left/ {\vphantom {{\sigma_{dc} } {\sigma_{opt} }}} \right. \kern-\nulldelimiterspace} {\sigma_{opt} }}$$

σ

dc

/

σ

opt

values of 33.8 and 31.8, respectively. In addition, GO and rGO can modify the surface and reduce the film surface roughness. The transparent conductive films are expected to be used in photoelectric devices.
Multi-level characteristics of TiOx transparent non-volatile resistive switching device by embedding SiO2 nanoparticles
Authors: Kwon Sera , Kim Min-Jung , Chung Kwun-Bum
Published: May 2021

TiOx-based resistive switching devices have recently attracted attention as a promising candidate for next-generation non-volatile memory devices. A number of studies have attempted to increase the structural density of resistive switching devices. The fabrication of a multi-level switching device is a feasible method for increasing the density of the memory cell. Herein, we attempt to obtain a non-volatile multi-level switching memory device that is highly transparent by embedding SiO2 nanoparticles (NPs) into the TiOx matrix (TiOx@SiO2 NPs). The fully transparent resistive switching device is fabricated with an ITO/TiOx@SiO2 NPs/ITO structure on glass substrate, and it shows transmittance over 95% in the visible range. The TiOx@SiO2 NPs device shows outstanding switching characteristics, such as a high on/off ratio, long retention time, good endurance, and distinguishable multi-level switching. To understand multi-level switching characteristics by adjusting the set voltages, we analyze the switching mechanism in each resistive state. This method represents a promising approach for high-performance non-volatile multi-level memory applications.
Role of robotic natural orifice specimen extraction surgery in colorectal neoplasms
Authors: Yao Hongliang , Li Tiegang , Chen Weidong , Lei Sanlin , Liu Kuijie , Liu Bo , Zhou Jiangjiao
Published: May 2021

Natural orifice specimen extraction surgery (NOSES) is especially suitable for colorectal surgery. Until now, most of the reports published were about laparoscopic NOSES, the reports about robotic NOSES are extremely rare. This study aims to explore the safety and feasibility of robotic NOSES for colorectal neoplasms. All patients underwent robotic NOSES from March 2016 to October 2019 in our hospital were enrolled for retrospective analysis. Clinicopathological data including patient characteristics, perioperative information and pathological information were collected and analyzed. According to the distance between tumor and anus or whether neoadjuvant chemoradiotherapy (nRCT) is performed, we grouped the cases and studied its influence on robotic NOSES. Also, we compared the previous reports on laparoscopic NOSES with our study and revealed advantages of robotic NOSES in terms of safety and feasibility. A total of 180 patients were enrolled. The average distance from the lower edge of the tumor to the anus was (8.64 ± 3.64) cm and maximum circumferential diameter (CDmax) of specimen was (3.5 ± 1.6) cm. In terms of safety, the average operation time, intraoperative blood loss, and postoperative hospital stay were (187.5 ± 78.3) min, (47.4 ± 34) mL, and (11.3 ± 7.5) days, respectively. In terms of feasibility, the average number of lymph node harvested was (14.8 ± 5). Robotic NOSES shows advantages in terms of safety and feasibility compared with laparoscopic NOSES. This procedure could not only be a safe procedure but also could achieve good oncological outcomes.
Rapid hybrid perovskite film crystallization from solution
Authors: Sánchez Sandy , Pfeifer Lukas , Vlachopoulos Nikolaos , Hagfeldt Anders
Published: May 2021

This review provides an overview of the hybrid-perovskite crystallization process for solar cells, unveiling the phenomena of thin film formation.
The use of metabolomics to reveal differences in functional substances of milk whey of dairy buffaloes raised at different altitudes
Authors: Pu Jinhui , Vinitchaikul Paramintra , Gu Zhaobing , Mao Huaming , Zhang Fulan
Published: May 2021

Buffalo milk from low-altitude region contains high levels of amino acids, vitamin B6, and carbohydrates, while buffalo milk from high-altitude region contains high free fatty acid content.
The modulatory effect and implication of gut microbiota on osteoporosis: from the perspective of “brain–gut–bone” axis
Authors: Zhang Yuan-Wei , Li Ying-Juan , Lu Pan-Pan , Dai Guang-Chun , Chen Xiang-Xu , Rui Yun-Feng
Published: May 2021

The “brain–gut–bone” axis is related to osteoporosis and can be a potential target for the prevention and treatment of it. The “brain–bone”, “gut–bone” and “brain–gut” connections are all closely relevant between the gut microbiota and osteoporosis.
Studies on the structure and chirality of A-motif in adenosine monophosphate nucleotide metal coordination complexes
Authors: Iqbal Muhammad Javed , Li Zhongkui , Khan Maroof Ahmad , Zhu Yanhong , Hussain Wajid , Su Hao , Qiu Qi-Ming , Shoukat Rizwan , Li Hui
Published: May 2021

Structure and chirality of A-motif.
A combined experimental and theoretical study of miconazole salts and cocrystals: crystal structures, DFT computations, formation thermodynamics and solubility improvement
Authors: Drozd K. V. , Manin A. N. , Voronin A. P. , Boycov D. E. , Churakov A. V. , Perlovich G. L.
Published: May 2021

Experimental and theoretical screening of multi-component crystal forms of miconazole (MCL), an antifungal drug, with ten aliphatic dicarboxylic acids was performed.
Reverse water-gas shift reaction over Pt/MoOx/TiO2: reverse Mars–van Krevelen mechanism via redox of supported MoOx
Authors: Mine Shinya , Yamaguchi Taichi , Ting Kah Wei , Maeno Zen , Siddiki S. M. A. Hakim , Oshima Kazumasa , Satokawa Shigeo , Shimizu Ken-ichi , Toyao Takashi
Published: May 2021

Pt/MoOx/TiO2 shows excellent catalytic performance for the reverse water-gas shift reaction at 250 °C via reverse Mars–van Krevelen mechanism.
Metal–organic-framework derived hollow manganese nickel selenide spheres confined with nanosheets on nickel foam for hybrid supercapacitors
Authors: Ameri Bahareh , Mohammadi Zardkhoshoui Akbar , Hosseiny Davarani Saied Saeed
Published: May 2021

An effective strategy is developed to fabricated hollow manganese nickel selenide spheres confined with nanosheets on nickel foam for hybrid supercapacitors.
Retraction: Ginsenoside Rf alleviates dysmenorrhea and inflammation through the BDNF-TrkB-CREB pathway in a rat model of endometriosis
Authors: Ross Philippa
Published: May 2021

Retraction of ‘Ginsenoside Rf alleviates dysmenorrhea and inflammation through the BDNF-TrkB-CREB pathway in a rat model of endometriosis’ by Xuying Qin et al., Food Funct., 2019, 10, 244–249, DOI: 10.1039/C8FO01839A.
Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4
Authors: Ouzon-Shubeita Hala , Schmaltz Lillian F. , Lee Seongmin
Published: May 2021

G:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guanine is stabilized by Arg468 of MBD4. To gain further insights into the mismatch discrimination mechanism of MBD4, we assessed the glycosylase activity of MBD4 toward various base pairs. In addition, we determined a crystal structure of MBD4 bound to T:O6-methylguanine-containing DNA, which suggests the O6 and N2 of purine and the O4 of pyrimidine are required to be a substrate for MBD4. To understand the role of the Arg468 finger in catalysis, we evaluated the glycosylase activity of MBD4 mutants, which revealed the guanidinium moiety of Arg468 may play an important role in catalysis. D560N/R468K MBD4 bound to T:G mismatched DNA shows that the side chain amine moiety of the Lys stabilizes the flipped-out thymine by a water-mediated phosphate pinching, while the backbone carbonyl oxygen of the Lys engages in hydrogen bonds with N2 of the estranged guanine. Comparison of various DNA glycosylase structures implies the guanidinium and amine moieties of Arg and Lys, respectively, may involve in discriminating between substrate mismatches and nonsubstrate base pairs.
Histone H3 N-terminal mimicry drives a novel network of methyl-effector interactions
Authors: Chen Jianji , Horton John , Sagum Cari , Zhou Jujun , Cheng Xiaodong , Bedford Mark T.
Published: May 2021

The reader ability of PHD fingers is largely limited to the recognition of the histone H3 N-terminal tail. Distinct subsets of PHDs bind either H3K4me3 (a transcriptional activator mark) or H3K4me0 (a transcriptional repressor state). Structural studies have identified common features among the different H3K4me3 effector PHDs, including (1) removal of the initiator methionine residue of H3 to prevent steric interference, (2) a groove where arginine-2 binds, and (3) an aromatic cage that engages methylated lysine-4. We hypothesize that some PHDs might have the ability to engage with non-histone ligands, as long as they adhere to these three rules. A search of the human proteome revealed an enrichment of chromatin-binding proteins that met these criteria, which we termed H3 N-terminal mimicry proteins (H3TMs). Seven H3TMs were selected, and used to screen a protein domain microarray for potential effector domains, and they all had the ability to bind H3K4me3-interacting effector domains. Furthermore, the binding affinity between the VRK1 peptide and the PHD domain of PHF2 is ∼3-fold stronger than that of PHF2 and H3K4me3 interaction. The crystal structure of PHF2 PHD finger bound with VRK1 K4me3 peptide provides a molecular basis for stronger binding of VRK1 peptide. In addition, a number of the H3TMs peptides, in their unmethylated form, interact with NuRD transcriptional repressor complex. Our findings provide in vitro evidence that methylation of H3TMs can promote interactions with PHD and Tudor domain-containing proteins and potentially block interactions with the NuRD complex. We propose that these interactions can occur in vivo as well.
Characterization of the structural determinants of the ubiquitin-dependent proteasomal degradation of human hepatic tryptophan 2,3-dioxygenase
Authors: Liu Yi , Kim Sung-Mi , Wang YongQiang , Karkashon Shay , Lewis-Ballester Ariel , Yeh Syun-Ru , Correia Maria Almira
Published: May 2021

Human hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ∼2.3 h, relative to an average t1/2 of ∼2–3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation pathway. Additionally, we identified 15 ubiquitination K-sites and demonstrated that Trp-binding to an exosite impeded its proteolytic degradation. Here, we further established autophagic-lysosomal degradation as an alternative back-up pathway for cellular hTDO degradation. In addition, with protein kinases A and C, we identified 13 phosphorylated Ser/Thr (pS/pT) sites. Mapping these pS/pT sites on the hTDO surface revealed their propinquity to acidic Asp/Glu (D/E) residues engendering negatively charged DEpSpT clusters vicinal to the ubiquitination K-sites over the entire protein surface. Through site-directed mutagenesis of positively charged patches of gp78, previously documented to interact with the DEpSpT clusters in other target proteins, we uncovered the likely role of the DEpSpT clusters in the molecular recognition of hTDO by gp78 and plausibly other E3 Ub-ligases. Furthermore, cycloheximide-chase analyses revealed the critical structural relevance of the disordered N- and C-termini not only in the Ub-ligase recognition, but also in the proteasome engagement. Together, the surface DEpSpT clusters and the N- and C-termini constitute an intrinsic bipartite degron for hTDO physiological turnover.
Glycogen synthase kinase 3β promotes osteosarcoma invasion and migration via regulating PTEN and phosphorylation of focal adhesion kinase
Authors: Mai Wei , Kong Lingyu , Yu Hongwei , Bao Junjie , Song Chunyu , Qu Guofan
Published: May 2021

Aim: Typical features of human osteosarcoma are highly invasive and migratory capacities. Our study aimed to investigate the roles of glycogen synthase kinase 3β (GSK3β) in human osteosarcoma metastasis.

Methods: GSK3β expressions in clinical osteosarcoma tissues with or without metastasis were examined by immunohistochemical staining. The expressions of GSK3β, p-GSK3βSer9, and p-GSK3βTyr216 in human osteoblast cells (hFOB1.19) and human osteosarcoma cells (MG63, SaOS-2, and U2-OS) were detected by Western blotting. The GSK3β activity was measured by non-radio isotopic in vitro kinase assay. Migration and invasion abilities of MG-63 cells treated with small-molecular GSK3β inhibitors were respectively examined by monolayer-based wound-healing assay and transwell assay. The mRNA expressions of GSK3β, matrix metalloproteinase-2 (MMP-2), MMP-9, phosphatase with tensin homology (PTEN), and focal adhesion kinase (FAK) were detected after siRNA transfection for 72 h. Meanwhile, protein expressions of GSK3β, FAK, p-FAKY397, PTEN, MMP-2, and MMP-9 were measured by Western blotting.

Results: Clinical osteosarcoma tissues with metastasis showed higher GSK3β expressions. MG63 and U2-OS cells that were easy to occur metastasis showed significantly higher expressions and activities of GSK3β than SaOS-2 cells. Inhibition of GSK3β with small-molecular GSK3β inhibitors in MG63 cells significantly attenuated cell migration and invasion. These effects were associated with reduced expressions of MMP-2 and MMP-9. Moreover, increased PTEN and decreased p-FAKY397 expressions were observed following GSK3β knockdown by siRNA transfection. Conclusion: GSK3β might promote osteosarcoma invasion and migration via pathways associated with PTEN and phosphorylation of FAK.
LncRNA UCA1 elevates the resistance of human leukemia cells to daunorubicin by the PI3K/AKT pathway via sponging miR-613
Authors: Yao Qiying , Zhang Li , Wang Yuchuan , Liu Junli , Yang Liu , Wang Yingjie
Published: May 2021

Acute leukemia is a hematological malignant tumor. Long non-coding RNA urothelial cancer-associated 1 (UCA1) is involved in the chemo-resistance of diverse cancers, but it is unclear whether UCA1 is associated with the sensitivity of acute leukemia cells to daunorubicin (DNR). DNR (100 nM) was selected for functional analysis. The viability, cell cycle progression, apoptosis, and invasion of treated acute leukemia cells (HL-60 and U-937) were evaluated by cell counting kit-8 (CCK-8) assay, flow cytometry assay, or transwell assay. Protein levels were detected with Western blot analysis. Expression patterns of UCA1 and miR-613 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between UCA1 and microRNA-613 (miR-613) was verified by dual-luciferase reporter assay. We observed that UCA1 expression was elevated in HL-60 and U-937cells. DNR constrained viability, cell cycle progression, invasion, and facilitated apoptosis of HL-60 and U-937 cells in a dose-dependent manner, but these impacts mediated by DNR were reverted after UCA1 overexpression. MiR-613 was down-regulated in HL-60 and U-937 cells, and UCA1 was verified as a miR-613 sponge. MiR-613 inhibitor reversed DNR treatment-mediated effects on viability, cell cycle progression, apoptosis, and invasion of HL-60 and U-937 cells, but these impacts mediated by miR-613 inhibitor were counteracted after UCA1 inhibition. Notably, the inactivation of the PI3K/AKT pathway caused by DNR treatment was reversed after miR-613 inhibitor introduction, but this influence mediated by miR-613 inhibitor was offset after UCA1 knockdown. In conclusion, UCA1 up-regulation facilitated the resistance of acute leukemia cells to DNR via the PI3K/AKT pathway by sponging miR-613.
Reduction of TMAO level enhances the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis
Authors: Shi Weihao , Huang Yijun , Yang Zhou , Zhu Liang , Yu Bo
Published: May 2021

It has been demonstrated that trimethylamine N-oxide (TMAO) serves as a driver of atherosclerosis, suggesting that reduction of TMAO level might be a potent method to prevent the progression of atherosclerosis. Herein, we explored the role of TMAO in the stability of carotid atherosclerotic plaques and disclosed the underlying mechanisms. The unstable carotid artery plaque models were established in C57/BL6 mice. L-carnitine (LCA) and methimazole (MMI) administration were applied to increase and reduce TMAO levels. Hematoxylin and eosin (H&E) staining, Sirius red, Perl’s staining, Masson trichrome staining and immunohistochemical staining with CD68 staining were used for histopathology analysis of the carotid artery plaque. M1 and M2 macrophagocyte markers were assessed by RT-PCR to determine the polarization of RAW264.7 cells. MMI administration for 2 weeks significantly decreased the plaque area, increased the thickness of the fibrous cap and reduced the size of the necrotic lipid cores, whereas 5-week of administration of MMI induced intraplate hemorrhage. LCA treatment further deteriorated the carotid atherosclerotic plaque but with no significant difference. In mechanism, we found that TMAO treatment impaired the M2 polarization and efferocytosis of RAW264.7 cells with no obvious effect on the M1 polarization. In conclusion, the present study demonstrated that TMAO reduction enhanced the stability of carotid atherosclerotic plaque through promoting macrophage M2 polarization and efferocytosis.
Validation of the functions and prognostic values of synapse-associated proteins in lower-grade glioma
Authors: Lin Han , Yang Yong , Hou Chongxian , Huang Yuqing , Zhou Liting , Zheng Jiantao , Lv Guangzhao , Mao Rui , Chen Shanwei , Xu Peihong , Zhou Yujun , Wang Peng , Zhou Dong
Published: May 2021

Synapse and synapse-associated proteins (SAPs) play critical roles in various neurodegeneration diseases and brain tumors. However, in lower-grade gliomas (LGG), SAPs have not been explored systematically. Herein, we are going to explore SAPs expression profile and its clinicopathological significance in LGG which can offer new insights to glioma therapy. In the present study, we integrate a list of SAPs that covered 231 proteins with synaptogenesis activity and post synapse formation. The LGG RNA-seq data were downloaded from GEO, TCGA and CGGA database. The prognosis associated SAPs in key modules of PPI (protein–protein interaction networks) was regarded as hub SAPs. Western blot, quantitative reverse transcription PCR (qRT-PCR) and immunochemistry results from HPA database were used to verify the expression of hub SAPs. There were 68 up-regulated SAPs and 44 down-regulated SAPs in LGG tissue compared with normal brain tissue. Data from function enrichment analysis revealed functions of differentially expressed SAPs in synapse organization and glutamatergic receptor pathway in LGGs. Survival analysis revealed that four SAPs, GRIK2, GABRD, GRID2 and ARC were correlate with the prognosis of LGG patients. Interestingly, we found that GABRD were up-regulated in LGG patients with seizures, indicating that SAPs may link to the pathogenesis of seizures in glioma patients. The four-SAPs signature was revealed as an independent prognostic factor in gliomas. Our study presented a novel strategy to assess the prognostic risks of LGGs, based on the expression of SAPs.
Head and Neck Cancer in a Rural U.S. Population: Quality of Life, Coping, Health Care Literacy, and Access to Services
Authors: Lowe Shawn M. , Nobriga Christina V.
Published: May 2021

Purpose

The aim of this study was to explore the beliefs, access, and motivations of individuals with head and neck cancer (HNC) living in a rural community in the United States, regarding their speech and swallowing deficits.

Method

A convenience sample of nine patient participants with HNC and nine caregiver participants completed in-depth, semistructured interviews regarding their experiences with HNC diagnosis and treatment. The researchers utilized a thematic networks approach to analyze the qualitative data obtained.

Results

Primary results of the study were a set of common themes emerging from 735 units for analysis, arranged into 34 basic themes, nine organizing themes, and four global themes. The resulting networks centered around quality of life impact, coping, health literacy, and access. Direct quotes from the participants are utilized to illustrate response categories.

Conclusions

Individuals with HNC and their caregivers living in rural communities in the United States appear to represent a unique subset of the HNC population. While they present similarly in most areas, they display unique tendencies in the areas of psychological coping, health literacy, and access. Provision of practical, pertinent information that can be accessed by patients and caregivers alike outside the hospital is suggested to better serve this community.
Moving Toward Accurate Assessment of Working Memory in Adults With Neurogenically Based Communication Disorders
Authors: Mohapatra Bijoyaa , Laures-Gore Jacqueline
Published: May 2021

Purpose

This article presents a viewpoint highlighting concerns regarding currently available assessments of working memory in adults with neurogenic communication disorders. Additionally, we provide recommendations for improving working memory assessment in this population.

Method

This viewpoint includes a critique of clinical and experimental working memory tests relevant to speech-language pathologists. We consider the terminology used to describe memory, as well as discuss language demands and test construction.

Results

Clinical and experimental testing of working memory in adults with neurogenic communication disorders is challenged due to theoretical, methodological, and practical limitations. The major limitations are characterized as linguistic and task demands, presentation and response modality effects, test administration, and scoring parameters. Taking these limitations into consideration, several modifications to working memory testing and their relevance to neurogenic populations are discussed.

Conclusions

The recommendations provided in this article can better guide clinicians and researchers to advocate for improved tests of working memory in adults with neurogenic communication disorders. Future research should continue to address these concerns and consider our recommendations.
Reliability of Outcome Measures to Assess Consonant Proficiency Following Cleft Palate Speech Intervention: The Percentage of Consonants Correct Metric and the Probe Scoring System
Authors: Alighieri Cassandra , Bettens Kim , Bruneel Laura , D'haeseleer Evelien , Van Gaever Ellen , Van Lierde Kristiane
Published: May 2021

Purpose

This study compared the inter- and intrarater reliability of the percentage of consonants correct (PCC) metrics and the probe scoring system between an experienced and a less experienced rater and between two experienced raters. In addition, these outcome measures' ability to reflect changes following speech intervention was measured.

Method

During Phase 1, two raters (Rater 1 with 5 years of experience in cleft-related speech disorders and Rater 2 with limited experience in cleft-related speech disorders) independently assessed 134 speech samples at the word and sentence levels, which were collected on different data points before, during, and following a cleft palate speech intervention. During Phase 2, a third rater (with 8 years of experience) analyzed 34 speech samples. The percentage of consonants correct–revised, the percentage of correct places and manners, and probe scores at the word and sentence levels were measured.

Results

Poor-to-moderate interreliability between Raters 1 and 2 was found due to differences in error classification. Interrater reliability between Raters 1 and 3 was very good for both the PCC metrics and the probe scores. The interrater reliability for the amount of targets elicited was lower compared to the interrater reliability for the amount of targets correct. The probe scoring system demonstrated a greater ability to detect changes toward the correct production of the target consonant compared to the PCC metrics.

Conclusions

Having an experience with the assessment of cleft-related speech disorders is a crucial factor to gain reliable results. The interrater reliability for the PCC metrics and the probe scoring system between two experienced raters did not differ, suggesting that both outcome measures can be used in cleft palate speech intervention studies. Despite the ability of the probe scoring system to detect changes, further research should provide insight in the benefits of this system both for research and clinical purposes.