bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium
Authors: Zhang Yong , Chen Jiayao , Fu Haijun , Kuang Shuhong , He Feng , Zhang Min , Shen Zongshan , Qin Wei , Lin Zhengmei , Huang Shuheng
Published: December 2021

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Age-related accumulation of advanced oxidation protein products promotes osteoclastogenesis through disruption of redox homeostasis
Authors: Zhuang Jingshen , Chen Xuebing , Cai Guixing , Wu Dizheng , Tu Chen , Zhu Siyuan , Huang Yusheng , Xu Ping , Zhong Zhaoming
Published: December 2021

Enhanced osteoclastogenesis is one of the major causes of age-related bone loss. Aging is accompanied by accumulation of advanced oxidation protein products (AOPPs). However, whether AOPPs accumulation contributing to the osteoclastogenesis with aging remains unclear. Here, we showed that AOPPs accumulation was associated with the enhanced osteoclastogenesis and deterioration of bone microstructure in aged mice. In vitro, AOPPs directly induced osteoclastogenesis by interaction with receptor activator of nuclear factor κ B (RANK) and the receptor for advanced glycation end products (RAGE) in the primary bone marrow monocytes. Bindings of AOPPs to RANK and RAGE were able to activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, trigger generation of reactive oxygen species, then induce phosphorylation of mitogen-activated protein kinases and c-fos, upregulation of the nuclear factor of activated T cell c1, eventually induce bone marrow monocytes to differentiate into mature osteoclasts. Chronic exposure to AOPPs enhanced osteoclastogenesis and bone loss in mice, which could be alleviated by NADPH oxidase inhibitor apocynin. Local injection of AOPPs into subperiosteal area induced bone resorption at the site of administration, which was similar to the effect of RANK ligand. Together, these results suggested that AOPPs could serve as a novel regulator of osteoclastogenesis and AOPPs accumulation might play an important role in the development of age-related bone loss.
TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia
Authors: Zhang Yahui , Hou Baohua , Liang Peiyu , Lu Xin , Wu Yifan , Zhang Xinyi , Fan Yuanteng , Liu Yumin , Chen Taoxiang , Liu Wanhong , Peng Biwen , Yin Jun , Han Song , He Xiaohua
Published: December 2021

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood. Here we identified that the TRPV1 (transient receptor potential vanilloid type 1) channel in microglia, as a Ca2+ influx-regulating channel, played an important role in NLRP3 inflammasome activation. Deletion or pharmacological blockade of TRPV1 inhibited NLRP3 inflammasome activation in microglia in vitro. Further research revealed that TRPV1 channel regulated ATP-induced NLRP3 inflammasome activation through mediating Ca2+ influx and phosphorylation of phosphatase PP2A in microglia. In addition, TRPV1 deletion could alleviate mice experimental autoimmune encephalomyelitis (EAE) and reduce neuroinflammation by inhibiting NLRP3 inflammasome activation. These data suggested that the TRPV1 channel in microglia can regulate NLRP3 inflammasome activation and consequently mediate neuroinflammation. Meanwhile, our study indicated that TRPV1–Ca2+–PP2A pathway may be a novel regulator of NLRP3 inflammasome activation, pointing to TRPV1 as a potential target for CNS inflammatory diseases.
Aldehyde dehydrogenase 3B2 promotes the proliferation and invasion of cholangiocarcinoma by increasing Integrin Beta 1 expression
Authors: Wang Yue , Li Kangshuai , Zhao Wei , Liu Zengli , Liu Jialiang , Shi Anda , Chen Tianli , Mu Wentao , Xu Yunfei , Pan Chang , Zhang Zongli
Published: December 2021

Aldehyde dehydrogenases (ALDHs) play an essential role in regulating malignant tumor progression; however, their role in cholangiocarcinoma (CCA) has not been elucidated. We analyzed the expression of ALDHs in 8 paired tumor and peritumor perihilar cholangiocarcinoma (pCCA) tissues and found that ALDH3B1 and ALDH3B2 were upregulated in tumor tissues. Further survival analysis in intrahepatic cholangiocarcinoma (iCCA, n = 27), pCCA (n = 87) and distal cholangiocarcinoma (dCCA, n = 80) cohorts have revealed that ALDH3B2 was a prognostic factor of CCA and was an independent prognostic factor of iCCA and pCCA. ALDH3B2 expression was associated with serum CEA in iCCA and dCCA, associated with tumor T stage, M stage, neural invasion and serum CA19-9 in pCCA. In two cholangiocarcinoma cell lines, overexpression of ALDH3B2 promoted cell proliferation and clone formation by promoting the G1/S phase transition. Knockdown of ALDH3B2 inhibited cell migration, invasion, and EMT in vitro, and restrained tumor metastasis in vivo. Patients with high expression of ALDH3B2 also have high expression of ITGB1 in iCCA, pCCA, and dCCA at both mRNA and protein levels. Knockdown of ALDH3B2 downregulated the expression of ITGB1 and inhibited the phosphorylation level of c-Jun, p38, and ERK. Meanwhile, knockdown of ITGB1 inhibited the promoting effect of ALDH3B2 overexpression on cell proliferation, migration, and invasion. ITGB1 is also a prognostic factor of iCCA, pCCA, and dCCA and double-positive expression of ITGB1 and ALDH3B2 exhibits better performance in predicting patient prognosis. In conclusion, ALDH3B2 promotes tumor proliferation and metastasis in CCA by regulating the expression of ITGB1 and upregulating its downstream signaling pathway. The double-positive expression of ITGB1 and ALDH3B2 serves as a better prognostic biomarker of CCA.
SYT8 promotes pancreatic cancer progression via the TNNI2/ERRα/SIRT1 signaling pathway
Authors: Fu Zhiping , Liang Xing , Shi Ligang , Tang Liang , Chen Danlei , Liu Anan , Shao Chenghao
Published: December 2021

Pancreatic cancer is a highly lethal malignancy due to failures of early detection and high metastasis in patients. While certain genetic mutations in tumors are associated with severity, the molecular mechanisms responsible for cancer progression are still poorly understood. Synaptotagmin-8 (SYT8) is a membrane protein that regulates hormone secretion and neurotransmission, and its expression is positively regulated by the promoter of the insulin gene in pancreatic islet cells. In this study, we identified a previously unknown role of SYT8 in altering tumor characteristics in pancreatic cancer. SYT8 levels were upregulated in patient tumors and contributed towards increased cell proliferation, migration, and invasion in vitro and in vivo. Increased SYT8 expression also promoted tumor metastasis in an in vivo tumor metastasis model. Furthermore, we showed that SYT8-mediated increase in tumorigenicity was regulated by SIRT1, a protein deacetylase previously known to alter cell metabolism in pancreatic lesions. SIRT1 expression was altered by orphan nuclear receptor ERRα and troponin-1 (TNNI2), resulting in cell proliferation and migration in an SYT8-dependent manner. Together, we identified SYT8 to be a central regulator of tumor progression involving signaling via the SIRT1, ERRα, and TNNI2 axis. This knowledge may provide the basis for the development of therapeutic strategies to restrict tumor metastasis in pancreatic cancer.
LncRNA LINC00667 aggravates the progression of hepatocellular carcinoma by regulating androgen receptor expression as a miRNA-130a-3p sponge
Authors: Qin Zhixiang , Liu Xiaohong , Li Zijing , Wang Ganggang , Feng Zhe , Liu Ye , Yang Hai , Tan Chengpeng , Zhang Zidong , Li Kun
Published: December 2021

Emerging studies have found long noncoding RNAs, widely expressed in eukaryotes, crucial regulators in the progression of human cancers, including hepatocellular carcinoma (HCC). Although the long intergenic noncoding RNA 667 (LINC00667) can promote the progression of a variety of cancer types, the expression pattern, the role in cancer progression, and the molecular mechanism involved in HCC remain unclear. This study aims to investigate the function and mechanism of LINC00667 in HCC progression. The effects of LINC00667 silencing in cell proliferation, cell migration, and cell invasion, and androgen receptor (AR) expression were determined with loss-of-function phenotypic analysis in Huh-7 and HCCLM3 cells, and subsequently testified in vivo in tumor growth. We found that the expression of LINC00667 was upregulated in HCC tissues and cell lines. Upregulation of LINC00667 was significantly associated with the unfavorable prognosis of HCC in our study patients. On the other hand, low expression of LINC00667 significantly inhibited the cell proliferation, cell migration and cell invasion of HCC in vitro and tumor growth in vivo. This inhibitory effect could be counteracted by miR-130a-3p inhibitor. LINC00667 reduced the inhibition of AR expression by miR-130a-3p, which correlated with the progression of HCC. Our finding suggests LINC00667 is a molecular sponge in the miR-130s-3p/AR signal pathway in the progression of HCC, in which it relieves the repressive function of miR-130a-3p on the AR expression. This indicates LINC00667 functions as a tumor promotor in promoting HCC progression through targeting miR-130a-3p/AR axis, making a novel biomarker and potential therapeutic target for HCC.
Simultaneous estimation of bi-directional causal effects and heritable confounding from GWAS summary statistics
Authors: Darrous Liza , Mounier Ninon , Kutalik Zoltán
Published: December 2021

Mendelian Randomisation (MR) is an increasingly popular approach that estimates the causal effect of risk factors on complex human traits. While it has seen several extensions that relax its basic assumptions, most suffer from two major limitations; their under-exploitation of genome-wide markers, and sensitivity to the presence of a heritable confounder of the exposure-outcome relationship. To overcome these limitations, we propose a Latent Heritable Confounder MR (LHC-MR) method applicable to association summary statistics, which estimates bi-directional causal effects, direct heritabilities, and confounder effects while accounting for sample overlap. We demonstrate that LHC-MR outperforms several existing MR methods in a wide range of simulation settings and apply it to summary statistics of 13 complex traits. Besides several concordant results with other MR methods, LHC-MR unravels new mechanisms (how disease diagnosis might lead to improved lifestyle) and reveals new causal effects (e.g. HDL cholesterol being protective against high systolic blood pressure), hidden from standard MR methods due to a heritable confounder of opposite effect direction.
A low-cost and shielding-free ultra-low-field brain MRI scanner
Authors: Liu Yilong , Leong Alex T. L. , Zhao Yujiao , Xiao Linfang , Mak Henry K. F. , Tsang Anderson Chun On , Lau Gary K. K. , Leung Gilberto K. K. , Wu Ed X.
Published: December 2021

Magnetic resonance imaging is a key diagnostic tool in modern healthcare, yet it can be cost-prohibitive given the high installation, maintenance and operation costs of the machinery. There are approximately seven scanners per million inhabitants and over 90% are concentrated in high-income countries. We describe an ultra-low-field brain MRI scanner that operates using a standard AC power outlet and is low cost to build. Using a permanent 0.055 Tesla Samarium-cobalt magnet and deep learning for cancellation of electromagnetic interference, it requires neither magnetic nor radiofrequency shielding cages. The scanner is compact, mobile, and acoustically quiet during scanning. We implement four standard clinical neuroimaging protocols (T1- and T2-weighted, fluid-attenuated inversion recovery like, and diffusion-weighted imaging) on this system, and demonstrate preliminary feasibility in diagnosing brain tumor and stroke. Such technology has the potential to meet clinical needs at point of care or in low and middle income countries.
Social stratification without genetic differentiation at the site of Kulubnarti in Christian Period Nubia
Authors: Sirak Kendra A. , Fernandes Daniel M. , Lipson Mark , Mallick Swapan , Mah Matthew , Olalde Iñigo , Ringbauer Harald , Rohland Nadin , Hadden Carla S. , Harney Éadaoin , Adamski Nicole , Bernardos Rebecca , Broomandkhoshbacht Nasreen , Callan Kimberly , Ferry Matthew , Lawson Ann Marie , Michel Megan , Oppenheimer Jonas , Stewardson Kristin , Zalzala Fatma , Patterson Nick , Pinhasi Ron , Thompson Jessica C. , Van Gerven Dennis , Reich David
Published: December 2021

Relatively little is known about Nubia’s genetic landscape prior to the influence of the Islamic migrations that began in the late 1st millennium CE. Here, we increase the number of ancient individuals with genome-level data from the Nile Valley from three to 69, reporting data for 66 individuals from two cemeteries at the Christian Period (~650–1000 CE) site of Kulubnarti, where multiple lines of evidence suggest social stratification. The Kulubnarti Nubians had ~43% Nilotic-related ancestry (individual variation between ~36–54%) with the remaining ancestry consistent with being  introduced through Egypt and ultimately deriving from an ancestry pool like that found in the Bronze and Iron Age Levant. The Kulubnarti gene pool – shaped over a millennium – harbors disproportionately female-associated West Eurasian-related ancestry. Genetic similarity among individuals from the two cemeteries supports a hypothesis of social division without genetic distinction. Seven pairs of inter-cemetery relatives suggest fluidity between cemetery groups. Present-day Nubians are not directly descended from the Kulubnarti Nubians, attesting to additional genetic input since the Christian Period.
Estimating the strength of selection for new SARS-CoV-2 variants
Authors: Dorp Christiaan H. van , Goldberg Emma E. , Hengartner Nick , Ke Ruian , Romero-Severson Ethan O.
Published: December 2021

Controlling the SARS-CoV-2 pandemic becomes increasingly challenging as the virus adapts to human hosts through the continual emergence of more transmissible variants. Simply observing that a variant is increasing in frequency is relatively straightforward, but more sophisticated methodology is needed to determine whether a new variant is a global threat and the magnitude of its selective advantage. We present two models for quantifying the strength of selection for new and emerging variants of SARS-CoV-2 relative to the background of contemporaneous variants. These methods range from a detailed model of dynamics within one country to a broad analysis across all countries, and they include alternative explanations such as migration and drift. We find evidence for strong selection favoring the D614G spike mutation and B.1.1.7 (Alpha), weaker selection favoring B.1.351 (Beta), and no advantage of R.1 after it spreads beyond Japan. Cutting back data to earlier time horizons reveals that uncertainty is large very soon after emergence, but that estimates of selection stabilize after several weeks. Our results also show substantial heterogeneity among countries, demonstrating the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.
Long decay length of magnon-polarons in BiFeO3/La0.67Sr0.33MnO3 heterostructures
Authors: Zhang Jianyu , Chen Mingfeng , Chen Jilei , Yamamoto Kei , Wang Hanchen , Hamdi Mohammad , Sun Yuanwei , Wagner Kai , He Wenqing , Zhang Yu , Ma Ji , Gao Peng , Han Xiufeng , Yu Dapeng , Maletinsky Patrick , Ansermet Jean-Philippe , Maekawa Sadamichi , Grundler Dirk , Nan Ce-Wen , Yu Haiming
Published: December 2021

Magnons can transfer information in metals and insulators without Joule heating, and therefore are promising for low-power computation. The on-chip magnonics however suffers from high losses due to limited magnon decay length. In metallic thin films, it is typically on the tens of micrometre length scale. Here, we demonstrate an ultra-long magnon decay length of up to one millimetre in multiferroic/ferromagnetic BiFeO3(BFO)/La0.67Sr0.33MnO3(LSMO) heterostructures at room temperature. This decay length is attributed to a magnon-phonon hybridization and is more than two orders of magnitude longer than that of bare metallic LSMO. The long-distance modes have high group velocities of 2.5 km s−1 as detected by time-resolved Brillouin light scattering. Numerical simulations suggest that magnetoelastic coupling via the BFO/LSMO interface hybridizes phonons in BFO with magnons in LSMO to form magnon-polarons. Our results provide a solution to the long-standing issue on magnon decay lengths in metallic magnets and advance the bourgeoning field of hybrid magnonics.
Biomimetic nanoparticles deliver mRNAs encoding costimulatory receptors and enhance T cell mediated cancer immunotherapy
Authors: Li Wenqing , Zhang Xinfu , Zhang Chengxiang , Yan Jingyue , Hou Xucheng , Du Shi , Zeng Chunxi , Zhao Weiyu , Deng Binbin , McComb David W. , Zhang Yuebao , Kang Diana D. , Li Junan , Carson William E. , Dong Yizhou
Published: December 2021

Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy.
SpookyNet: Learning force fields with electronic degrees of freedom and nonlocal effects
Authors: Unke Oliver T. , Chmiela Stefan , Gastegger Michael , Schütt Kristof T. , Sauceda Huziel E. , Müller Klaus-Robert
Published: December 2021

Machine-learned force fields combine the accuracy of ab initio methods with the efficiency of conventional force fields. However, current machine-learned force fields typically ignore electronic degrees of freedom, such as the total charge or spin state, and assume chemical locality, which is problematic when molecules have inconsistent electronic states, or when nonlocal effects play a significant role. This work introduces SpookyNet, a deep neural network for constructing machine-learned force fields with explicit treatment of electronic degrees of freedom and nonlocality, modeled via self-attention in a transformer architecture. Chemically meaningful inductive biases and analytical corrections built into the network architecture allow it to properly model physical limits. SpookyNet improves upon the current state-of-the-art (or achieves similar performance) on popular quantum chemistry data sets. Notably, it is able to generalize across chemical and conformational space and can leverage the learned chemical insights, e.g. by predicting unknown spin states, thus helping to close a further important remaining gap for today’s machine learning models in quantum chemistry.
Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects
Authors: Ying Lei , Wang Luyao , Guo Kaiwen , Hou Yushu , Li Na , Wang Shuyi , Liu Xingfeng , Zhao Qijin , Zhou Jie , Zhao Longwei , Niu Jianlou , Chen Chuchu , Song Lintao , Hou Shaocong , Kong Lijuan , Li Xiaokun , Ren Jun , Li Pingping , Mohammadi Moosa , Huang Zhifeng
Published: December 2021

Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks β-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.
Nanoparticles and photochemistry for native-like transmembrane protein footprinting
Authors: Sun Jie , Liu Xiaoran Roger , Li Shuang , He Peng , Li Weikai , Gross Michael L.
Published: December 2021

Mass spectrometry-based footprinting can probe higher order structure of soluble proteins in their native states and serve as a complement to high-resolution approaches. Traditional footprinting approaches, however, are hampered for integral membrane proteins because their transmembrane regions are not accessible to solvent, and they contain hydrophobic residues that are generally unreactive with most chemical reagents. To address this limitation, we bond photocatalytic titanium dioxide (TiO2) nanoparticles to a lipid bilayer. Upon laser irradiation, the nanoparticles produce local concentrations of radicals that penetrate the lipid layer, which is made permeable by a simultaneous laser-initiated Paternò–Büchi reaction. This approach achieves footprinting for integral membrane proteins in liposomes, helps locate both ligand-binding residues in a transporter and ligand-induced conformational changes, and reveals structural aspects of proteins at the flexible unbound state. Overall, this approach proves effective in intramembrane footprinting and forges a connection between material science and biology.
Rapid increase in dichloromethane emissions from China inferred through atmospheric observations
Authors: An Minde , Western Luke M. , Say Daniel , Chen Liqu , Claxton Tom , Ganesan Anita L. , Hossaini Ryan , Krummel Paul B. , Manning Alistair J. , Mühle Jens , O’Doherty Simon , Prinn Ronald G. , Weiss Ray F. , Young Dickon , Hu Jianxin , Yao Bo , Rigby Matthew
Published: December 2021

With the successful implementation of the Montreal Protocol on Substances that Deplete the Ozone Layer, the atmospheric abundance of ozone-depleting substances continues to decrease slowly and the Antarctic ozone hole is showing signs of recovery. However, growing emissions of unregulated short-lived anthropogenic chlorocarbons are offsetting some of these gains. Here, we report an increase in emissions from China of the industrially produced chlorocarbon, dichloromethane (CH2Cl2). The emissions grew from 231 (213–245) Gg yr−1 in 2011 to 628 (599–658) Gg yr−1 in 2019, with an average annual increase of 13 (12–15) %, primarily from eastern China. The overall increase in CH2Cl2 emissions from China has the same magnitude as the global emission rise of 354 (281−427) Gg yr−1 over the same period. If global CH2Cl2 emissions remain at 2019 levels, they could lead to a delay in Antarctic ozone recovery of around 5 years compared to a scenario with no CH2Cl2 emissions.
Application of green synthesized WO3-poly glutamic acid nanobiocomposite for early stage biosensing of breast cancer using electrochemical approach
Authors: Nasrollahpour Hassan , Naseri Abdolhossein , Rashidi Mohammad-Reza , Khalilzadeh Balal
Published: December 2021

Biopolymer films have drawn growing demand for their application in the point of care domain owing to their biocompatibility, eco-friendly, and eligibility for in vivo analyses. However, their poor conductivity restricts their sensitivity in diagnostics. For high-quality electrochemical biosensor monitoring, two vital factors to be greatly paid attention are the effective merge of amplification modifiers with transducing surface and the superior linking across the recognition interface. Here, we introduce an enzyme-free electrochemical biosensor based on electrosynthesized biocompatible WO3/poly glutamic acid nano-biocomposites to address the hardships specific to the analysis of circulating proteins clinical samples. In addition to its green synthesis route, the poor tendency of both components of the prepared nano-biocomposite to amine groups makes it excellent working in untreated biological samples with high contents of proteins. Several electrochemical and morphological investigations (SEM, EDX, and dot mapping) were fulfilled to gain a reliable and trustful standpoint of the framework. By using this nanobiosensor, the concentration of HER-2 was detectable as low as 1 fg mL−1 with a wide linear response between 1 ng mL−1 and 1 fg mL−1. Meanwhile, the protocol depicted ideal specificity, stability, and reproducibility for the detection of HER-2 protein in untreated serum samples of breast cancer patients.
Emergency activations for chest pain and ventricular arrhythmias related to regional COVID-19 across the US
Authors: Aung Sidney , Vittinghoff Eric , Nah Gregory , Lin Anthony , Joyce Sean , Mann N. Clay , Marcus Gregory M.
Published: December 2021

Evidence that patients may avoid healthcare facilities for fear of COVID-19 infection has heightened the concern that true rates of myocardial infarctions have been under-ascertained and left untreated. We analyzed data from the National Emergency Medical Services Information System (NEMSIS) and incident COVID-19 infections across the United States (US) between January 1, 2020 and April 30, 2020. Grouping events by US Census Division, multivariable adjusted negative binomial regression models were utilized to estimate the relationship between COVID-19 and EMS cardiovascular activations. After multivariable adjustment, increasing COVID-19 rates were associated with less activations for chest pain and non-ST-elevation myocardial infarctions. Simultaneously, increasing COVID-19 rates were associated with more activations for cardiac arrests, ventricular fibrillation, and ventricular tachycardia. Although direct effects of COVID-19 infections may explain these discordant observations, these findings may also arise from patients delaying or avoiding care for myocardial infarction, leading to potentially lethal consequences.
Fever is associated with earlier antibiotic onset and reduced mortality in patients with sepsis admitted to the ICU
Authors: Dias Aileen , Gomez Vitoria Campanha , Viola Luciana Rosa , Rodrigues Anna Carolina Pedrazani , Weber Stefanie Piber , Tartaro Luiza , da Silva Marques Leonardo , Boniatti Márcio Manozzo
Published: December 2021

To evaluate the association of body temperature with mortality in septic patients admitted to the ICU from the ward. In addition, we intend to investigate whether the timing of antibiotic administration was different between febrile and afebrile patients and whether this difference contributed to mortality. This is a retrospective cohort study that included sepsis patients admitted to the ICU from the ward between July 2017 and July 2019. Antibiotic administration was defined as the initiation of antimicrobial treatment or the expansion of the antimicrobial spectrum within 48 h prior to admission to the ICU. Regarding vital signs, the most altered vital sign in the 48 h prior to admission to the ICU was considered. Two hundred and eight patients were included in the final analysis. Antibiotic administration occurred earlier in patients with fever than in patients without fever. Antibiotic administration occurred before admission to the ICU in 27 (90.0%) patients with fever and in 101 (64.7%) patients without fever (p = 0.006). The mortality rate in the ICU was 88 in 176 (50.0%; 95% CI 42.5–57.5%) patients without fever and 7 in 32 (21.9%; 95% CI 6.7–37.0%) patients with fever (p = 0.004). In the multivariate analysis, absence of fever significantly increased the risk of ICU mortality (OR 3.462; 95% CI 1.293–9.272). We found an inverse association between body temperature and mortality in patients with sepsis admitted to the ICU from the ward. Although antibiotic administration was earlier in patients with fever and precocity was associated with reduced mortality, the time of antibiotic administration did not fully explain the lower mortality in these patients.
Speech token detection and discrimination in individual infants using functional near-infrared spectroscopy
Authors: Mao Darren , Wunderlich Julia , Savkovic Borislav , Jeffreys Emily , Nicholls Namita , Lee Onn Wah , Eager Michael , McKay Colette M.
Published: December 2021

Speech detection and discrimination ability are important measures of hearing ability that may inform crucial audiological intervention decisions for individuals with a hearing impairment. However, behavioral assessment of speech discrimination can be difficult and inaccurate in infants, prompting the need for an objective measure of speech detection and discrimination ability. In this study, the authors used functional near-infrared spectroscopy (fNIRS) as the objective measure. Twenty-three infants, 2 to 10 months of age participated, all of whom had passed newborn hearing screening or diagnostic audiology testing. They were presented with speech tokens at a comfortable listening level in a natural sleep state using a habituation/dishabituation paradigm. The authors hypothesized that fNIRS responses to speech token detection as well as speech token contrast discrimination could be measured in individual infants. The authors found significant fNIRS responses to speech detection in 87% of tested infants (false positive rate 0%), as well as to speech discrimination in 35% of tested infants (false positive rate 9%). The results show initial promise for the use of fNIRS as an objective clinical tool for measuring infant speech detection and discrimination ability; the authors highlight the further optimizations of test procedures and analysis techniques that would be required to improve accuracy and reliability to levels needed for clinical decision-making.
A convergence research perspective on graduate education for sustainable urban systems science
Authors: Lobo José , Alberti Marina , Allen-Dumas Melissa , Bettencourt Luís M. A. , Beukes Anni , Bojórquez Tapia Luis A. , Chen Wei-Qiang , Dodge Anne , Neal Zachary , Perreira Anna , Pfeiffer Deirdre , Revi Aromar , Roberts Debra , Rozenblat Céline , Shutters Shade , Smith Michel E. , Stokes Eleanor , Strumsky Deborah , Wu Jianguo
Published: December 2021

Sustainable urban systems (SUS) science is a new science integrating work across established and emerging disciplines, using diverse methods, and addressing issues at local, regional, national, and global scales. Advancing SUS requires the next generation of scholars and practitioners to excel at synthesis across disciplines and possess the skills to innovate in the realms of research, policy, and stakeholder engagement. We outline key tenets of graduate education in SUS, informed by historical and global perspectives. The sketch is an invitation to discuss how graduates in SUS should be trained to engage with the challenges and opportunities presented by continuing urbanization.
Heterobimetallic uranyl(vi) alkoxides of lanthanoids: formation through simple ligand exchange
Authors: Grödler Dennis , Weidemann Martin L. , Lichtenberg Andreas , Greven Tobias , Nickstadt Robin , Haydo Malek , Wickleder Mathias , Klein Axel , Johrendt Dirk , Mathur Sanjay , Zegke Markus , Raauf Aida
Published: December 2021

Uranyl bends and stretches as lanthanoids coordinate.
Reaction–diffusion phenomena in antagonistic bipolar diffusion fields
Authors: Dúzs Brigitta , Szalai István
Published: December 2021

The bipolar antagonistic diffusion field spatially localizes the intermediates of a reaction. This bipolar spatial control results in localized wave phenomena in a nonlinear activatory–inhibitory reaction.
Thiazetidin-2-ylidenes as four membered N-heterocyclic carbenes: theoretical studies and the generation of complexes with N+ center
Authors: Dubey Gurudutt , Mahawar Nutan , Singh Tejender , Saha Nirjhar , Sahoo Subash C. , Bharatam Prasad V.
Published: December 2021

Thiazetin-2-ylidene as a quantum chemically designed four-membered N-heterocyclic carbene possesses high singlet stability and nucleophilicity and forms NHC→N+←(thiazetidin-2-ylidene) systems.
Polymerisation of styrene using pincer type amine functionalized azo aromatic complexes of Co(ii) as catalysts
Authors: Goswami Bappaditya , Khatua Manas , Samanta Subhas
Published: December 2021

Azo-aromatic complexes of Co(ii), 1–3 have shown efficient polymerization of styrene upon activation of MMAO. The isolated polystyrenes have high Mw (32.9 to 144.0 kg mol−1) in a narrow range of Đ values (1.1–1.8) and good plastic/soft behavior.
Diruthenium aryl compounds – tuning of electrochemical responses and solubility
Authors: Miller-Clark Lyndsy A. , Christ Peter E. , Ren Tong
Published: December 2021

The variation of the substituents (X = 3,5-(OMe)2; 3-iPrO) on the bridging ligand results in improved solubility of Ru2-aryl compounds, while the aryl substitution significantly influences the potentials of the Ru2-based redox couples.
Avoiding water reservoir effects in ALD of functional complex alkali oxides by using O3 as the oxygen source
Authors: Sønsteby Henrik H. , Killi Veronica A.-L. K. , Rykkje Linn M. , Bickford Justin R. , Martin Eric G. , Hoffman Robert C. , Nilsen Ola
Published: December 2021

A new ozone-based route for excellent control of complex alkali oxides by ALD.
Correction: Tuning the selectivity of electrochemical levulinic acid reduction to 4-hydroxyvaleric acid: a monomer for biocompatible and biodegradable plastics
Authors: Lucas Francisco W. S. , Fishler Yuval , Holewinski Adam
Published: December 2021

Correction for ‘Tuning the selectivity of electrochemical levulinic acid reduction to 4-hydroxyvaleric acid: a monomer for biocompatible and biodegradable plastics’ by Francisco W. S. Lucas et al., Green Chem., 2021, 23, 9154–9164, DOI: 10.1039/D1GC02826J.
Hybrid skin chips for toxicological evaluation of chemical drugs and cosmetic compounds
Authors: Lee Jong Seung , Kim Jin , Cui Baofang , Kim Su Kyeom , Cho Sun-A , An Susun , Cho Seung-Woo
Published: December 2021

Hybrid skin models for safety tests of drugs and cosmetics for topical application.
Discovery of a highly selective and ultra-sensitive colorimetric fluorescent probe for malononitrile and its applications in living cells and zebrafish
Authors: Wang Xin , Cheng Siyu , Liu Caiyun , Zhang Yan , Su Meijun , Rong Xiaodi , Zhu Hanchuang , Yu Miaohui , Sheng Wenlong , Zhu Baocun
Published: December 2021

A selective and ultra-sensitive colorimetric fluorescent probe was discovered to detect malononitrile in living cells and zebrafish.
Diverse “roof shaped” chiral diamidophosphites: palladium coordination and catalytic applications
Authors: Gavrilov Konstantin N. , Chuchelkin Ilya V. , Gavrilov Vladislav K. , Zheglov Sergey V. , Firsin Ilya D. , Trunina Valeria M. , Zamilatskov Ilya A. , Tyurin Vladimir S. , Tafeenko Victor A. , Chernyshev Vladimir V. , Zimarev Vladislav S. , Goulioukina Nataliya S.
Published: December 2021

“Roof shaped” chiral diamidophosphites of various structures and denticities were obtained and tested in Pd-catalyzed asymmetric allylic substitution.
In situ detection of fluid media based on a three-dimensional dendritic silver surface-enhanced Raman scattering substrate
Authors: Li Sha , Wang Zezhou , Shao Yunpeng , Zhang Kai , Mei Linyu , Wang Junyuan
Published: December 2021

A simple substitution reaction was used to grow 3D dendritic silver structures in microfluidic channels, and a highly active SERS detection platform was formed. The system can realize in situ detection of 10−10 mol L−1 R6G solution.
Transition-metal nitride halide dielectrics for transition-metal dichalcogenide transistors
Authors: Rostami Osanloo Mehrdad , Saadat Ali , Van de Put Maarten L. , Laturia Akash , Vandenberghe William G.
Published: December 2021

Using first-principles calculations, we investigate six transition-metal nitride halides as potential vdW dielectrics for transition metal dichalcogenide channel transistors. We identify the best combinations for the p-MOS transistor technology.
Carrier dynamics at trench defects in InGaN/GaN quantum wells revealed by time-resolved cathodoluminescence
Authors: Kusch Gunnar , Comish Ella J. , Loeto Kagiso , Hammersley Simon , Kappers Menno J. , Dawson Phil , Oliver Rachel A. , Massabuau Fabien C.-P.
Published: December 2021

Time-resolved cathodoluminescence is an emerging tool to investigate carrier recombination mechanisms at defects in semiconductors – here applied to trench defects in InGaN quantum wells.
Fast and versatile thermo-osmotic flows with a pinch of salt
Authors: Herrero Cecilia , De San Féliciano Michael , Merabia Samy , Joly Laurent
Published: December 2021

Fast and versatile thermally induced flows can be obtained on slipping charged surfaces with applications for waste heat harvesting.
Visible-light-mediated regioselective synthesis of novel thiazolo[3,2-b][1,2,4]triazoles: advantageous synthetic application of aqueous conditions
Authors: Aggarwal Ranjana , Hooda Mona , Kumar Prince , Torralba Mari Carmen
Published: December 2021

A regioselective synthesis of novel thiazolo[3,2-b][1,2,4]triazoles has been establishedviaa visible-light-facilitated reaction of unsymmetrical α-bromodiketones with 3-mercapto[1,2,4]triazoles under aqueous conditions.
The synthesis of aryl-heteroaryl derivatives via the RhIII-catalyzed heteroarylation of arenes and heteroaromatic boronates
Authors: Wang Huai-Wei , Wu Jia-Xue , Li Da-Cheng , Qiao Yu-Han , Yao Qing-Xia , Sun Wen-Can , Dou Jian-Min
Published: December 2021

An efficient RhIII-catalyzed strategy to synthesize ortho-heteroarylated ketoxime structural scaffolds via directed C–H activation/heteroarylation involving arenes and heteroaryl organoboron reagents has been developed.
Palladium oxidative addition complex-enabled synthesis of amino-substituted indolyl-4(3H)-quinazolinones and their antitumor activity evaluation
Authors: Jiang Zhi , Zhao Dan-Dan , Hu Yu-Tao , Rao Yong , Guo Shi-Yao , Xu Yao-Hao , Li Qingjiang , Huang Zhi-Shu
Published: December 2021

Palladium-based oxidative addition complex (OAC)-enabled C–N cross-couplings of aryl halides with amines toward the synthesis of amino-substituted indolyl-4(3H)-quinazolinones and their antitumor activity evaluation have been studied.
Cationic ring-opening polymerization of a five membered cyclic dithiocarbonate having a tertiary amine moiety
Authors: Krishnamurthy Suvratha , Yoshida Yoshiaki , Endo Takeshi
Published: December 2021

A dibenzylamine derived cyclic dithiocarbonate (1) undergoes ring-opening polymerization due to the greater reactivity of exocyclic sulfur compared to the tertiary amine with methyl triflate.
Luminescence property switching in 1D supramolecular polymerization of organic donor–π-acceptor chromophores
Authors: Ali Sk. Mursed , Santra Subrata , Mondal Arun , Kolay Soumya , Roy Lisa , Molla Mijanur Rahaman
Published: December 2021

The naphthalene monoimide building block endows with amide functionality undergoes supramolecular polymerization in a J type fashion in a particular co-solvent composition. This leads to luminescent property switching as a result of PET effect.
Three birds with one stone: a single AIEgen for dual-organelle imaging, cell viability evaluation and photodynamic cancer cell ablation
Authors: Zhang Yuewei , Wang Shuohang , Zhang Ning , Wang Xiaodong , Zan Qi , Fan Li , Yu Xue , Shuang Shaomin , Dong Chuan
Published: December 2021

We report the first single AIEgen that has great potential for dual-imaging of mitochondria/LDs, detection of cell viability and simultaneously photodynamic ablation of cancer cells.
Drug-likeness scoring based on unsupervised learning
Authors: Lee Kyunghoon , Jang Jinho , Seo Seonghwan , Lim Jaechang , Kim Woo Youn
Published: December 2021

A new quantification method of drug-likeness based on unsupervised learning. The method only uses drug molecules as training set without any non-drug-like molecules.
Porous boron nitride nanofibers as effective nanofillers for poly(vinyl alcohol) composite hydrogels with excellent self-healing performances
Authors: Gao Xiangqian , Deng Tiantian , Huang Xindi , Yu Mengmeng , Li Danyang , Lin Jing , Yu Chao , Tang Chengchun , Huang Yang
Published: December 2021

New composite hydrogels with excellent self-healing properties were prepared by combining poly(vinyl alcohol) (PVA) and boron nitride nanofibers (BNNFs) via a facile one-pot assembly method.
A high-voltage solar rechargeable device based on a CoPi/BiVO4 faradaic junction
Authors: Zhang Junzhe , Jiang Dongjian , Wang Pin , Zhong Jun , Sun Gengzhi , Yao Yingfang , Luo Wenjun , Zou Zhigang
Published: December 2021

CoPi is used as an energy storage material in a two-electrode solar rechargeable device for the first time, which exhibits the highest working voltage among all previously reported devices.
Simultaneous dual pyrolysis synthesis of heterostructured FeCo/C porous hollow microspheres for highly efficient microwave absorption
Authors: Liu Ran , Du Gaiping , Liao Bin , Xiao Weixin , An Zhenguo , Zhang Jingjie
Published: December 2021

Benefiting from the unique hollow structure, synergistic effects between dielectric and magnetic phases, excellent impedance matching and high attenuation ability, FeCo/C porous hollow microspheres show superior microwave absorption performance.
Enhancing organic photovoltaic performance with 3D-transport dual nonfullerene acceptors
Authors: Dai Shuixing , Li Mengyang , Xin Jingming , Lu Guanyu , Xue Peiyao , Zhao Yong , Liu Yang , Sun Mingliang , Yu Liangmin , Tang Zheng , Lu Guanghao , Ma Wei , Zhan Xiaowei
Published: December 2021

Dual nonfullerene acceptors Y6:FINIC with 3D charge transport features are used to fabricate sequential-process heterojunction (SHJ) and bulk heterojunction (BHJ) organic solar cells, and the SHJ outperforms the BHJ.
An A-site management and oxygen-deficient regulation strategy with a perovskite oxide electrocatalyst for the oxygen evolution reaction
Authors: Liu Changhai , Ji Dingwei , Shi Hong , Wu Zhenyu , Huang Hui , Kang Zhenhui , Chen Zhidong
Published: December 2021

LaNiO3 samples with different levels of Sn-cation substitution at the A-site were fabricated and they exhibited observably electrocatalytic activity toward the OER, which was attributing to the enhanced Ni 3d–O 2p covalency and oxygen vacancies .
Uniform lithium nucleation/deposition regulated by N/S co-doped carbon nanospheres towards ultra-stable lithium metal anodes
Authors: Zhang Fei , Liu Ping , Tian Yue , Wu Jinfeng , Wang Xuewei , Li Huili , Liu Xiaoyan
Published: December 2021

N and S co-doped mesoporous carbon nanospheres show strong affinity towards lithium ions, which dramatically reduce the lithium nucleation barrier and improve the stability of SEI layer, boosting a dendrite-free lithium metal anode.
π⋯π interaction directed 2D FeNi-LDH nanosheets from 2D Hofmann-MOFs for the oxygen evolution reaction
Authors: Huo Jia-Min , Wang Ying , Meng Jie , Zhao Xin-Yi , Zhai Quan-Guo , Jiang Yu-Cheng , Hu Man-Cheng , Li Shu-Ni , Chen Yu
Published: December 2021

A two-dimensional (2D) MOFs transformation strategy was introduced to synthesize FeNi layered double hydroxides (FeNi LDHs) in NaBH4 solution, which show excellent OER catalytic activity in alkaline media.
Regucalcin ameliorates doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria
Authors: Mohammed Noor A. , Hakeem Israa J. , Hodges Nikolas , Michelangeli Francesco
Published: December 2021

Doxorubicin (DOX) is a potent anticancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 h over a range of concentrations, and the LC50 was determined to be 7 µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 h, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically induced cell stress.