bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational adjustment to interfacial interaction with carbonized polymer dots enabling efficient large-area perovskite light-emitting diodes
Authors: Yang Fan , Zeng Qingsen , Dong Wei , Kang Chunyuan , Qu Zexing , Zhao Yue , Wei Haotong , Zheng Weitao , Zhang Xiaoyu , Yang Bai
Published: May 2023

Film uniformity of solution-processed layers is the cornerstone of large-area perovskite light-emitting diodes, which is often determined by the ‘coffee-ring effect’. Here we demonstrate a second factor that cannot be ignored is the solid-liquid interface interaction between substrate and precursor and can be optimized to eliminate rings. A perovskite film with rings can be formed when cations dominate the solid-liquid interface interaction; whereas smooth and homogeneous perovskite emitting layers are generated when anions and anion groups dominate the interaction. This is due to the fact that the type of ions anchored to the substrate can determine how the subsequent film grows. This interfacial interaction is adjusted using carbonized polymer dots, who also orient the perovskite crystals and passivate their buried traps, enabling a 225 mm2 large-area perovskite light-emitting diode with a high efficiency of 20.2%.
Suppressing fear in the presence of a safety cue requires infralimbic cortical signaling to central amygdala
Authors: Ng Ka , Pollock Michael , Escobedo Abraham , Bachman Brent , Miyazaki Nanami , Bartlett Edward L. , Sangha Susan
Published: May 2023

Stressful events can have lasting and impactful effects on behavior, especially by disrupting normal regulation of fear and reward processing. Accurate discrimination among environmental cues predicting threat, safety or reward adaptively guides behavior. Post-traumatic stress disorder (PTSD) represents a condition in which maladaptive fear persists in response to explicit safety-predictive cues that coincide with previously learned threat cues, but without threat being present. Since both the infralimbic cortex (IL) and amygdala have each been shown to be important for fear regulation to safety cues, we tested the necessity of specific IL projections to the basolateral amygdala (BLA) or central amygdala (CeA) during safety recall. Male Long Evans rats were used since prior work showed female Long Evans rats did not acquire the safety discrimination task used in this study. Here, we show the infralimbic projection to the central amygdala was necessary for suppressing fear cue-induced freezing in the presence of a learned safety cue, and the projection to the basolateral amygdala was not. The loss of discriminative fear regulation seen specifically during IL->CeA inhibition is similar to the behavioral disruption seen in PTSD individuals that fail to regulate fear in the presence of a safety cue.
Dual role of ANGPTL8 in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis
Authors: Gao Yujiu , Yuan Yue , Wen Shu , Chen Yanghui , Zhang Zongli , Feng Ying , Jiang Bin , Ma Shinan , Hu Rong , Fang Chen , Ruan Xuzhi , Yuan Yahong , Fang Xinggang , Luo Chao , Meng Zhongji , Wang Xiaoli , Guo Xingrong
Published: May 2023

The interplay between hepatocellular carcinoma (HCC) cells and the tumor microenvironment is essential for hepatocarcinogenesis, but their contributions to HCC development are incompletely understood. We assessed the role of ANGPTL8, a protein secreted by HCC cells, in hepatocarcinogenesis and the mechanisms through which ANGPTL8 mediates crosstalk between HCC cells and tumor-associated macrophages. Immunohistochemical, Western blotting, RNA-Seq, and flow cytometry analyses of ANGPTL8 were performed. A series of in vitro and in vivo experiments were conducted to reveal the role of ANGPTL8 in the progression of HCC. ANGPTL8 expression was positively correlated with tumor malignancy in HCC, and high ANGPTL8 expression was associated with poor overall survival (OS) and disease-free survival (DFS). ANGPTL8 promoted HCC cell proliferation in vitro and in vivo, and ANGPTL8 KO inhibited the development of HCC in both DEN-induced and DEN-plus-CCL4-induced mouse HCC tumors. Mechanistically, the ANGPTL8–LILRB2/PIRB interaction promoted polarization of macrophages to the immunosuppressive M2 phenotype in macrophages and recruited immunosuppressive T cells. In hepatocytes, ANGPTL8-mediated stimulation of LILRB2/PIRB regulated the ROS/ERK pathway and upregulated autophagy, leading to the proliferation of HCC cells. Our data support the notion that ANGPTL8 has a dual role in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis.
SYK-mediated epithelial cell state is associated with response to c-Met inhibitors in c-Met-overexpressing lung cancer
Authors: Zhou Ji , Zhang Xu-Chao , Xue Shan , Dai Mengdi , Wang Yueliang , Peng Xia , Chen Jianjiao , Wang Xinyi , Shen Yanyan , Qin Hui , Chen Bi , Zheng Yu , Gao Xiwen , Xie Zuoquan , Ding Jian , Jiang Handong , Wu Yi-Long , Geng Meiyu , Ai Jing
Published: May 2023

Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer (NSCLC) patients according to the predicted response to c-Met inhibitors (c-Metis), yet the overall clinical benefit of this strategy is quite limited. Notably, c-Met protein overexpression, which occurs in approximately 20–25% of NSCLC patients, has not yet been clearly defined as a clinically useful biomarker. An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking. Herein, we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status. Furthermore, TGF-β1 treatment resulted in SYK transcriptional downregulation, increased Sp1-mediated transcription of FRA1, and restored the mesenchymal state, which conferred resistance to c-Metis. Clinically, a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3% and longer progression-free survival with c-Meti treatment than other patients. SYK negativity coupled with TGF-β1 positivity conferred de novo and acquired resistance. In summary, SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state. Furthermore, our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy.
Hypoxia-mediated promotion of glucose metabolism in non-small cell lung cancer correlates with activation of the EZH2/FBXL7/PFKFB4 axis
Authors: Zhou Jing , Lin Yang , Kang Xiuhua , Liu Zhicheng , Zou Juntao , Xu Fei
Published: May 2023

F-box/LRR-repeat protein 7 (FBXL7) was predicted as a differentially expressed E3 ubiquitin ligase in non-small cell lung cancer (NSCLC), which has been suggested to influence cancer growth and metastasis. In this study, we aimed to decipher the function of FBXL7 in NSCLC and delineate the upstream and downstream mechanisms. FBXL7 expression was verified in NSCLC cell lines and GEPIA-based tissue samples, after which the upstream transcription factor of FBXL7 was bioinformatically identified. The substrate PFKFB4 of the FBXL7 was screened out by tandem affinity purification coupled with mass-spectrometry (TAP/MS). FBXL7 was downregulated in NSCLC cell lines and tissue samples. FBXL7 ubiquitinated and degraded PFKFB4, thus suppressing glucose metabolism and malignant phenotypes of NSCLC cells. Hypoxia-induced HIF-1α upregulation elevated EZH2 and inhibited FBXL7 transcription and reduced its expression, thus promoting PFKFB4 protein stability. By this mechanism, glucose metabolism and the malignant phenotype were enhanced. In addition, knockdown of EZH2 impeded tumor growth through the FBXL7/PFKFB4 axis. In conclusion, our work reveals that the EZH2/FBXL7/PFKFB4 axis plays a regulatory role in glucose metabolism and tumor growth of NSCLC, which is expected to be potential biomarkers for NSCLC.
IGF2BP3 promotes adult myocardial regeneration by stabilizing MMP3 mRNA through interaction with m6A modification
Authors: Li Simeng , Shen Siman , Xu Hao , Cai Shuyun , Yuan Xiaodong , Wang Changsen , Zhang Xiaojun , Chen Suyun , Chen Jianning , Shi De-Li , Zhang Liangqing
Published: May 2023

Myocardial infarction that causes damage to heart muscle can lead to heart failure. The identification of molecular mechanisms promoting myocardial regeneration represents a promising strategy to improve cardiac function. Here we show that IGF2BP3 plays an important role in regulating adult cardiomyocyte proliferation and regeneration in a mouse model of myocardial infarction. IGF2BP3 expression progressively decreases during postnatal development and becomes undetectable in the adult heart. However, it becomes upregulated after cardiac injury. Both gain- and loss-of-function analyses indicate that IGF2BP3 regulates cardiomyocyte proliferation in vitro and in vivo. In particular, IGF2BP3 promotes cardiac regeneration and improves cardiac function after myocardial infarction. Mechanistically, we demonstrate that IGF2BP3 binds to and stabilizes MMP3 mRNA through interaction with N6-methyladenosine modification. The expression of MMP3 protein is also progressively downregulated during postnatal development. Functional analyses indicate that MMP3 acts downstream of IGF2BP3 to regulate cardiomyocyte proliferation. These results suggest that IGF2BP3-mediated post-transcriptional regulation of extracellular matrix and tissue remodeling contributes to cardiomyocyte regeneration. They should help to define therapeutic strategy for ameliorating myocardial infarction by inducing cell proliferation and heart repair.
Prioritization of potential causative genes for schizophrenia in placenta
Authors: Ursini Gianluca , Di Carlo Pasquale , Mukherjee Sreya , Chen Qiang , Han Shizhong , Kim Jiyoung , Deyssenroth Maya , Marsit Carmen J. , Chen Jia , Hao Ke , Punzi Giovanna , Weinberger Daniel R.
Published: May 2023

Our earlier work has shown that genomic risk for schizophrenia converges with early life complications in affecting risk for the disorder and sex-biased neurodevelopmental trajectories. Here, we identify specific genes and potential mechanisms that, in placenta, may mediate such outcomes. We performed TWAS in healthy term placentae (N = 147) to derive candidate placental causal genes that we confirmed with SMR; to search for placenta and schizophrenia-specific associations, we performed an analogous analysis in fetal brain (N = 166) and additional placenta TWAS for other disorders/traits. The analyses in the whole sample and stratifying by sex ultimately highlight 139 placenta and schizophrenia-specific risk genes, many being sex-biased; the candidate molecular mechanisms converge on the nutrient-sensing capabilities of placenta and trophoblast invasiveness. These genes also implicate the Coronavirus-pathogenesis pathway and showed increased expression in placentae from a small sample of SARS-CoV-2-positive pregnancies. Investigating placental risk genes for schizophrenia and candidate mechanisms may lead to opportunities for prevention that would not be suggested by study of the brain alone.
Flattened 1D fragments of fullerene C60 that exhibit robustness toward multi-electron reduction
Authors: Hayakawa Masahiro , Sunayama Naoyuki , Takagi Shu I. , Matsuo Yu , Tamaki Asuka , Yamaguchi Shigehiro , Seki Shu , Fukazawa Aiko
Published: May 2023

Fullerenes are compelling molecular materials owing to their exceptional robustness toward multi-electron reduction. Although scientists have attempted to address this feature by synthesizing various fragment molecules, the origin of this electron affinity remains unclear. Several structural factors have been suggested, including high symmetry, pyramidalized carbon atoms, and five-membered ring substructures. To elucidate the role of the five-membered ring substructures without the influence of high symmetry and pyramidalized carbon atoms, we herein report the synthesis and electron-accepting properties of oligo(biindenylidene)s, a flattened one-dimensional fragment of fullerene C60. Electrochemical studies corroborated that oligo(biindenylidene)s can accept electrons up to equal to the number of five-membered rings in their main chains. Moreover, ultraviolet/visible/near-infrared absorption spectroscopy revealed that oligo(biindenylidene)s exhibit enhanced absorption covering the entire visible region relative to C60. These results highlight the significance of the pentagonal substructure for attaining stability toward multi-electron reduction and provide a strategy for the molecular design of electron-accepting π-conjugated hydrocarbons even without electron-withdrawing groups.
Parasitic capacitance modeling and measurements of conductive yarns for e-textile devices
Authors: Qu Ziqi , Zhu Zhechen , Liu Yulong , Yu Mengxia , Ye Terry Tao
Published: May 2023

Conductive yarns have emerged as a viable alternative to metallic wires in e-Textile devices, such as antennas, inductors, interconnects, and more, which are integral components of smart clothing applications. But the parasitic capacitance induced by their micro-structure has not been fully understood. This capacitance greatly affects device performance in high-frequency applications. We propose a lump-sum and turn-to-turn model of an air-core helical inductor constructed from conductive yarns, and systematically analyze and quantify the parasitic elements of conductive yarns. Using three commercial conductive yarns as examples, we compare the frequency response of copper-based and yarn-based inductors with identical structures to extract the parasitic capacitance. Our measurements show that the unit-length parasitic capacitance of commercial conductive yarns ranges from 1 fF/cm to 3 fF/cm, depending on the yarn’s microstructure. These measurements offer significant quantitative estimation of conductive yarn parasitic elements and provide valuable design and characterization guidelines for e-Textile devices.
RagD auto-activating mutations impair MiT/TFE activity in kidney tubulopathy and cardiomyopathy syndrome
Authors: Sambri Irene , Ferniani Marco , Campostrini Giulia , Testa Marialuisa , Meraviglia Viviana , de Araujo Mariana E. G. , Dokládal Ladislav , Vilardo Claudia , Monfregola Jlenia , Zampelli Nicolina , Vecchio Blanco Francesca Del , Torella Annalaura , Ruosi Carolina , Fecarotta Simona , Parenti Giancarlo , Staiano Leopoldo , Bellin Milena , Huber Lukas A. , De Virgilio Claudio , Trepiccione Francesco , Nigro Vincenzo , Ballabio Andrea
Published: May 2023

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are “auto- activating”, even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation of “canonical” mTORC1 substrates, such as S6K. By using HeLa and HK-2 cell lines, human induced pluripotent stem cell-derived cardiomyocytes and patient-derived primary fibroblasts, we show thatRRAGDauto-activating mutations lead to inhibition of TFEB and TFE3 nuclear translocation and transcriptional activity, which impairs the response to lysosomal and mitochondrial injury. These data suggest that inhibition of MiT/TFE factors plays a key role in kidney tubulopathy and cardiomyopathy syndrome.
Structural insights into cardiolipin replacement by phosphatidylglycerol in a cardiolipin-lacking yeast respiratory supercomplex
Authors: Hryc Corey F. , Mallampalli Venkata K. P. S. , Bovshik Evgeniy I. , Azinas Stavros , Fan Guizhen , Serysheva Irina I. , Sparagna Genevieve C. , Baker Matthew L. , Mileykovskaya Eugenia , Dowhan William
Published: May 2023

Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV1III2IV1) and a supercomplex (III2IV1) isolated from a cardiolipin-lacking Saccharomyces cerevisiae mutant at 3.2-Å and 3.3-Å resolution, respectively, and demonstrate that phosphatidylglycerol in III2IV1 occupies similar positions as cardiolipin in IV1III2IV1. Lipid-protein interactions within these complexes differ, which conceivably underlies the reduced level of IV1III2IV1 and high levels of III2IV1 and free III2 and IV in mutant mitochondria. Here we show that anionic phospholipids interact with positive amino acids and appear to nucleate a phospholipid domain at the interface between the individual complexes, which dampen charge repulsion and further stabilize interaction, respectively, between individual complexes.
Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies
Authors: Zhang Fengwen , Jenkins Jesse , de Carvalho Renan V. H. , Nakandakari-Higa Sandra , Chen Teresia , Abernathy Morgan E. , Baharani Viren A. , Nyakatura Elisabeth K. , Andrew David , Lebedeva Irina V. , Lorenz Ivo C. , Hoffmann H.-Heinrich , Rice Charles M. , Victora Gabriel D. , Barnes Christopher O. , Hatziioannou Theodora , Bieniasz Paul D.
Published: May 2023

Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolete by the emergence of mAb-resistant virus variants. Here we report the generation of a set of six human mAbs that bind the human angiotensin-converting enzyme-2 (hACE2) receptor, rather than the SARS-CoV-2 spike protein. We show that these antibodies block infection by all hACE2 binding sarbecoviruses tested, including SARS-CoV-2 ancestral, Delta and Omicron variants at concentrations of ~7–100 ng ml−1. These antibodies target an hACE2 epitope that binds to the SARS-CoV-2 spike, but they do not inhibit hACE2 enzymatic activity nor do they induce cell-surface depletion of hACE2. They have favourable pharmacology, protect hACE2 knock-in mice against SARS-CoV-2 infection and should present a high genetic barrier to the acquisition of resistance. These antibodies should be useful prophylactic and treatment agents against any current or future SARS-CoV-2 variants and might be useful to treat infection with any hACE2-binding sarbecoviruses that emerge in the future.
Photon-trapping-enhanced avalanche photodiodes for mid-infrared applications
Authors: Chen Dekang , March Stephen D. , Jones Andrew H. , Shen Yang , Dadey Adam A. , Sun Keye , McArthur J. Andrew , Skipper Alec M. , Xue Xingjun , Guo Bingtian , Bai Junwu , Bank Seth R. , Campbell Joe C.
Published: May 2023

The fast development of mid-wave infrared photonics has increased the demand for high-performance photodetectors that operate in this spectral range. However, the signal-to-noise ratio, regarded as a primary figure of merit for mid-wave infrared detection, is strongly limited by the high dark current in narrow-bandgap materials. Therefore, conventional mid-wave infrared photodetectors such as HgCdTe require cryogenic temperatures to avoid excessively high dark current. To address this challenge, we report an avalanche photodiode design using photon-trapping structures to enhance the quantum efficiency and minimize the absorber thickness to suppress the dark current. The device exhibits high quantum efficiency and dark current density that is nearly three orders of magnitude lower than that of the state-of-the-art HgCdTe avalanche photodiodes and nearly two orders lower than that of previously reported AlInAsSb avalanche photodiodes that operate at 2 µm. Additionally, the bandwidth of these avalanche photodiodes reaches ~7 GHz, and the gain–bandwidth product is over 200 GHz; both are more than four times those of previously reported 2 µm avalanche photodiodes.
Single-cell multi-omics in the medicinal plant Catharanthus roseus
Authors: Li Chenxin , Wood Joshua C. , Vu Anh Hai , Hamilton John P. , Rodriguez Lopez Carlos Eduardo , Payne Richard M. E. , Serna Guerrero Delia Ayled , Gase Klaus , Yamamoto Kotaro , Vaillancourt Brieanne , Caputi Lorenzo , O’Connor Sarah E. , Robin Buell C.
Published: May 2023

Advances in omics technologies now permit the generation of highly contiguous genome assemblies, detection of transcripts and metabolites at the level of single cells and high-resolution determination of gene regulatory features. Here, using a complementary, multi-omics approach, we interrogated the monoterpene indole alkaloid (MIA) biosynthetic pathway in Catharanthus roseus, a source of leading anticancer drugs. We identified clusters of genes involved in MIA biosynthesis on the eight C. roseus chromosomes and extensive gene duplication of MIA pathway genes. Clustering was not limited to the linear genome, and through chromatin interaction data, MIA pathway genes were present within the same topologically associated domain, permitting the identification of a secologanin transporter. Single-cell RNA-sequencing revealed sequential cell-type-specific partitioning of the leaf MIA biosynthetic pathway that, when coupled with a single-cell metabolomics approach, permitted the identification of a reductase that yields the bis-indole alkaloid anhydrovinblastine. We also revealed cell-type-specific expression in the root MIA pathway.
Targeted dream incubation at sleep onset increases post-sleep creative performance
Authors: Horowitz Adam Haar , Esfahany Kathleen , Gálvez Tomás Vega , Maes Pattie , Stickgold Robert
Published: May 2023

The link between dreams and creativity has been a topic of intense speculation. Recent scientific findings suggest that sleep onset (known as N1) may be an ideal brain state for creative ideation. However, the specific link between N1 dream content and creativity has remained unclear. To investigate the contribution of N1 dream content to creative performance, we administered targeted dream incubation (a protocol that presents auditory cues at sleep onset to introduce specific themes into dreams) and collected dream reports to measure incorporation of the selected theme into dream content. We then assessed creative performance using a set of three theme-related creativity tasks. Our findings show enhanced creative performance and greater semantic distance in task responses following a period of N1 sleep as compared to wake, corroborating recent work identifying N1 as a creative sweet spot and offering novel evidence for N1 enabling a cognitive state with greater associative divergence. We further demonstrate that successful N1 dream incubation enhances creative performance more than N1 sleep alone. To our knowledge, this is the first controlled experiment investigating a direct role of incubating dream content in the enhancement of creative performance.
Socio-cultural practices on the use of beetle grubs as food and feed in western Kenya
Authors: Wanjala Martin N. , Orinda Mary , Nyongesah John M. , Tanga Chrysantus M. , Subramanian Sevgan , Kassie Menale , Egonyu James P.
Published: May 2023

We examined the socio-cultural practices on the use of beetle grubs as food and feed in western Kenya by interviewing 211 randomly selected households and conducting seven focus group discussions in Bungoma, Kakamega, Busia, and Trans Nzoia counties. The grubs were used as food and feed in ~ 39% and 78% of the households, respectively. The perceived benefits of the grubs for human consumption were nutritiousness and no linkage to allergies. The grubs were perceived to enhance animal weight gain and increase poultry egg laying. They were also perceived to recycle nutrients from organic waste, and clean the environment. Toasting and roasting were the dominant methods of preparing the grubs. Lack of knowledge on the grub nutritional benefits and stigma were key deterrents to their consumption. About 66% of the respondents expressed willingness to farm the grubs if the market and rearing protocols are available. Almost 98% of the respondents lacked knowledge of the beetle biology, indicating limited capacity to conserve them. The practices on the use of beetle grubs as food and feed differed across counties and by gender, age, marital status and education level. Strategies for sustainable use of the grubs as food and feed have been proposed and new research directions highlighted.
A novel mucopolysaccharidosis type II mouse model with an iduronate-2-sulfatase-P88L mutation
Authors: Mashima Ryuichi , Ohira Mari , Okuyama Torayuki , Onodera Masafumi , Takada Shuji
Published: May 2023

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder characterized by an accumulation of glycosaminoglycans (GAGs), including heparan sulfate, in the body. Major manifestations involve the central nerve system (CNS), skeletal deformation, and visceral manifestations. About 30% of MPS II is linked with an attenuated type of disease subtype with visceral involvement. In contrast, 70% of MPS II is associated with a severe type of disease subtype with CNS manifestations that are caused by the human iduronate-2-sulfatase (IDS)-Pro86Leu (P86L) mutation, a common missense mutation in MPS II. In this study, we reported a novel Ids-P88L MPS II mouse model, an analogous mutation to human IDS-P86L. In this mouse model, a significant impairment of IDS enzyme activity in the blood with a short lifespan was observed. Consistently, the IDS enzyme activity of the body, as assessed in the liver, kidney, spleen, lung, and heart, was significantly impaired. Conversely, the level of GAG was elevated in the body. A putative biomarker with unestablished nature termed UA-HNAc(1S) (late retention time), one of two UA-HNAc(1S) species with late retention time on reversed-phase separation,is a recently reported MPS II-specific biomarker derived from heparan sulfate with uncharacterized mechanism. Thus, we asked whether this biomarker might be elevated in our mouse model. We found a significant accumulation of this biomarker in the liver, suggesting that hepatic formation could be predominant. Finally, to examine whether gene therapy could enhance IDS enzyme activity in this model, the efficacy of the nuclease-mediated genome correction system was tested. We found a marginal elevation of IDS enzyme activity in the treated group, raising the possibility that the effect of gene correction could be assessed in this mouse model. In conclusion, we established a novel Ids-P88L MPS II mouse model that consistently recapitulates the previously reported phenotype in several mouse models.
Direct visualization of carbon black aggregates in nitrile butadiene rubber by THz near-field microscope
Authors: Moon Youngil , Lee Haneol , Jung Jaekap , Han Haewook
Published: May 2023

The use of filling agents for rubber reinforcement is beneficial in various industrial applications, and several experimental methods have been used to study the effect of fillers on rubber. However, due to the lack of a suitable imaging technique, filler dispersion and distribution in rubber cannot be easily displayed. Thus, we utilize the THz near-field microscope (THz-NFM) to directly visualize the distribution of carbon black (CB) aggregates in nitrile butadiene rubber (NBR). The THz time-domain spectroscopy (THz-TDS) was used to evaluate the optical properties of the NBR specimens. Results revealed significant indices contrast between CB and NBR at the THz regime, which was attributed to the variation in electrical conductivities. The micrographs of NBR in the THz-NFM revealed the distribution of CB aggregates. The area fraction (AF) of the CB aggregates was calculated using a binary thresholding algorithm to compare with the transmission electron microscope method. Both methods yielded comparable AF values, suggesting, for the first time, that CB can be detected in the NBR without preprocessing the specimens.
An observational study on factors associated with ICU mortality in Covid-19 patients and critical review of the literature
Authors: Lavrentieva Athina , Kaimakamis Evangelos , Voutsas Vassileios , Bitzani Militsa
Published: May 2023

The novel pandemic caused by SARS-CoV-2 has been associated with increased burden on healthcare system. Recognizing the variables that independently predict death in COVID-19 is of great importance. The study was carried out prospectively in a single ICU in northern Greece. It was based on the collection of data during clinical practice in 375 adult patients who were tested positive for SARS-CoV-2 between April 2020 and February 2022. All patients were intubated due to acute respiratory insufficiency and received Invasive Mechanical Ventilation. The primary outcome was ICU mortality. Secondary outcomes were 28-day mortality and independent predictors of mortality at 28 days and during ICU hospitalization. For continuous variables with normal distribution, t-test was used for means comparison between two groups and one-way ANOVA for multiple comparisons. When the distribution was not normal, comparisons were performed using the Mann–Whitney test. Comparisons between discrete variables were made using the x2 test, whereas the binary logistic regression was employed for the definition of factors affecting survival inside the ICU and after 28 days. Of the total number of patients intubated due to COVID-19 during the study period, 239 (63.7%) were male. Overall, the ICU survival was 49.6%, whereas the 28-day survival reached 46.9%. The survival rates inside the ICU for the four main viral variants were 54.9%, 50.3%, 39.7% and 50% for the Alpha, Beta, Delta and Omicron variants, respectively. Logistic regressions for outcome revealed that the following parameters were independently associated with ICU survival: wave, SOFA @day1, Remdesivir use, AKI, Sepsis, Enteral Insufficiency, Duration of ICU stay and WBC. Similarly, the parameters affecting the 28-days survival were: duration of stay in ICU, SOFA @day1, WBC, Wave, AKI and Enteral Insufficiency. In this observational cohort study of critically ill COVID-19 patients we report an association between mortality and the wave sequence, SOFA score on admission, the use of Remdesivir, presence of AKI, presence of gastrointestinal failure, sepsis and WBC levels. Strengths of this study are the large number of critically ill COVID-19 patients included, and the comparison of the adjusted mortality rates between pandemic waves within a two year-study period.
Association between stress and eating behaviour among Malaysian adolescents prior to examination
Authors: Shah Nurfazlinda Md , Aghamohammadi Nasrin , Thangiah Nithiah , Ng Ai Kah , Majid Hazreen Abdul
Published: May 2023

Studies have shown the prevalence of mental health and obesity among adolescents is at increasing trend due to urbanisation and changes in lifestyle. This study is to investigate the level of stress and its impact on eating behaviour among Malaysian adolescents. A total of 797 multi-ethnic Malaysian secondary school student participated in this cross-sectional study. Data was collected two weeks prior to final year examination. A validated Cohen Perceived Stress Scale questionnaire was used to assess the stress level with subsample analysis of 261 participants’ saliva cortisol level. A validated Child Eating Behaviour questionnaire was used to explore eating behaviours. There were 29.1% adolescents having high stress with the mean saliva cortisol 3.8 nmol/L. A positive correlation was observed between perceived stress and emotional overeating; stronger among urban (r = 0.32), female (r = 0.31), underweight (r = 0.34) and moderately stressed adolescents (r = 0.24). In addition, a positive correlation was found between perceived stress and food responsiveness; strongest among Malay (r = 0.23), male (r = 0.24), underweight (r = 0.30) and adolescents with high perceived stress (r = 0.24). The perceived stress level prior to exam period affects the emotional eating and external eating patterns of adolescents.
Comparative study of ternary hybrid nanofluids with role of thermal radiation and Cattaneo-Christov heat flux between double rotating disks
Authors: Noreen Sobia , Farooq Umar , Waqas Hassan , Fatima Nahid , Alqurashi M. S. , Imran Muhammad , Akgül Ali , Bariq Abdul
Published: May 2023

Heat and mass transfer are crucial to numerous technical and commercial operations, including air conditioning, machinery power collectors, crop damage, processing food, heat transfer mechanisms, and cooling, among numerous others. The fundamental purpose of this research is to use the Cattaneo-Christov heat flux model to disclose an MHD flow of ternary hybrid nanofluid through double discs. The results of a heat source and a magnetic field are therefore included in a system of PDEs that model the occurrences. These are transformed into an ODE system using similarity replacements. The first-order differential equations that emerge are then handled using the computational technique Bvp4c shooting scheme. The Bvp4c function in MATLAB is used to numerically solve the governing equations. The influence of the key important factors on velocity, temperature, nanoparticles concentration, and is illustrated visually. Furthermore, increasing the volume fraction of nanoparticles improves thermal conduction, increasing the heat transfer rate at the top disc. The graph indicates that a slight increase in melting parameter rapidly declines the velocity distribution profile of nanofluid. The temperature profile was boosted due to the growing outcomes of the Prandtl number. The increasing variations of the thermal relaxation parameter decline the thermal distribution profile. Furthermore, for some exceptional instances, the obtained numerical answers were compared to previously disclosed data, yielding a satisfactory compromise. We believe that this discovery will have far-reaching ramifications in engineering, medicine, and the field of biomedical technology. Additionally, this model can be used to examine biological mechanisms, surgical techniques, nano-pharmacological drug delivery systems, and the therapy of diseases like cholesterol using nanotechnology.
Food Taboo and associated factors among pregnant women attending antenatal clinics at Bahir Dar City, North West Ethiopia, 2021: cross-sectional study
Authors: Abere Meseret , Azene Abebaw Gedef
Published: May 2023

Food taboo is any unacceptable food items in the society that arise mainly based on religious, cultural, historical and social principles. Developing countries faced the triple burden of malnutrition of under nutrition, micronutrient deficiencies and overeating. Food taboos have great effect on pregnant women through prohibited essential food and/or drinks. There is a paucity of study conducted in food taboo practice among pregnant women in Ethiopia. This study aimed to assess the prevalence of food taboo practice and associated factors among pregnant women attending antenatal care (ANC) at Bahir Dar city, 2020. Institutional based cross-sectional study design was conducted among 421 pregnant women attending antenatal care clinics. Stratified sampling technique was used to approach the study participants, and interviewer administered questionnaire was used for data collection. Binary logistic regression analysis was conducted to identify predictors. The prevalence of food taboo practices among pregnant women was 27.5% (95% CI 23.2–31.8%) at the Bahir Dar city. Most food items avoided during pregnancy were meat, honey, milk, fruit and cereals. Reasons for avoidance of these food items were plastered on the fetal head, and making fatty baby which is difficult for deliver. Maternal age 20–30 years (AOR = 8.39, 95% CI 3.49–20.14), more than 30 years [AOR = 10.56, 95% CI (2.00, 51.74)], more than 2 parity [AOR = 9.83 95% CI (2.79, 34.70)], no previous experience of the ANC visit [AOR = 2.68, 95% CI (1.26, 5.73)], and no information about nutrition [AOR = 4.55, 95% CI (1.77, 11.70)] were significantly associated with practice of food taboo. This study revealed that prevalence of food taboo is high during pregnancy. The implications of this study that needs strengthening nutrition counseling components of ANC follow-up and health professionals needs to design and implement strategic health communication intended to reorient misconceptions and myths for the pregnant women regarding the food taboo.
Origin variations and brachial plexus relationship of the dorsal scapular artery
Authors: Lai Kuen-Cherng , Ho Han-Chen
Published: May 2023

The dorsal scapular artery can either be a direct branch of the subclavian artery or a branch of the transverse cervical artery. Origin variation is related to its relationship with the brachial plexus. Anatomical dissection was performed on 79 sides of 41 formalin-embalmed cadavers in Taiwan. The origin of the dorsal scapular artery and the variations of its brachial plexus relationship were scrutinized and analyzed. Results showed that the dorsal scapular artery originated most frequently from the transverse cervical artery (48%), followed by the direct branch from the third part (25%) and the second part (22%) of the subclavian artery and from the axillary artery (5%). Only 3% of the dorsal scapular artery passed through the brachial plexus if its origin was the transverse cervical artery. However, 100% and 75% of the dorsal scapular artery passed through the brachial plexus when they were direct branches of the second and the third part of the subclavian artery, respectively. Suprascapular arteries were also found to pass through the brachial plexus when they were direct branches from the subclavian artery, but all passed over or under the brachial plexus if they originated from the thyrocervical trunk or transverse cervical artery. Variations in the origin and course of arteries around the brachial plexus are of immense value not only to the basic anatomical knowledge but also to clinical practices such as supraclavicular brachial plexus block and head and neck reconstruction with pedicled or free flaps.
Association of Molnupiravir and Nirmatrelvir-Ritonavir with reduced mortality and sepsis in hospitalized omicron patients: a territory-wide study
Authors: Wai Abraham Ka-chung , Lee Teddy Tai-loy , Chan Sunny Ching-long , Chan Crystal Ying , Yip Edmond Tsz-fung , Luk Luke Yik-fung , Ho Joshua Wing-kei , So Kevin Wang-leong , Tsui Omar Wai-kiu , Lam Man-lok , Lee Shi-yeow , Yamamoto Tafu , Tong Chak-kwan , Wong Man-sing , Wong Eliza Lai-yi , Rainer Timothy Hudson
Published: May 2023

This study evaluates the association between antivirals (Molnupiravir and Nirmatrelvir-Ritonavir) and all-cause and respiratory mortality and organ dysfunction among high-risk COVID-19 patients during an Omicron outbreak. Two cohorts, Nirmatrelvir-Ritonavir versus control and Molnupiravir versus control, were constructed with inverse probability treatment weighting to balance baseline characteristics. Cox proportional hazards models evaluated the association of their use with all-cause mortality, respiratory mortality, and all-cause sepsis (a composite of circulatory shock, respiratory failure, acute liver injury, coagulopathy, and acute liver impairment). Patients recruited were hospitalized and diagnosed with the COVID-19 Omicron variant between February 22, 2022 and April 15, 2022, and followed up until May 15, 2022. The study included 17,704 patients. There were 4.67 and 22.7 total mortalities per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio, − 18.1 [95% CI − 23.0 to − 13.2]; hazard ratio, 0.18 [95% CI, 0.11–0.29]). There were 6.64 and 25.9 total mortalities per 1000 person-days in the Molnupiravir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, − 19.3 [95% CI − 22.6 to − 15.9]; hazard ratio, 0.23 [95% CI 0.18–0.30]). In all-cause sepsis, there were 13.7 and 35.4 organ dysfunction events per 1000 person-days in the Nirmatrelvir-Ritonavir and control groups respectively before adjustment (weighted incidence rate ratio per 1000 person-days, − 21.7 [95% CI − 26.3 to − 17.1]; hazard ratio, 0.44 [95% CI 0.38–0.52]). There were 23.7 and 40.8 organ dysfunction events in the Molnupiravir and control groups respectively before adjustment (weighted incidence ratio per 1000 person-days, − 17.1 [95% CI, − 20.6 to − 13.6]; hazard ratio, 0.63 [95% CI 0.58–0.69]). Among COVID-19 hospitalized patients, use of either Nirmatrelvir-Ritonavir or Molnupiravir compared with no antiviral use was associated with a significantly lower incidence of 28-days all-cause and respiratory mortality and sepsis.
Use of machine learning to improve the estimation of conductivity and permittivity based on longitudinal relaxation time T1 in magnetic resonance at 7 T
Authors: Hernandez Daniel , Kim Kyoung-Nam
Published: May 2023

Electrical property tomography (EPT) is a noninvasive method that uses magnetic resonance imaging (MRI) to estimate the conductivity and permittivity of tissues, and hence, can be used as a biomarker. One branch of EPT is based on the correlation of water and relaxation time T1 with the conductivity and permittivity of tissues. This correlation was applied to a curve-fitting function to estimate electrical properties, it was found to have a high correlation between permittivity and T1 however the computation of conductivity based on T1 requires to estimate the water content. In this study, we developed multiple phantoms with several ingredients that modify the conductivity and permittivity and explored the use of machine learning algorithms to have a direct estimation of conductivity and permittivity based on MR images and the relaxation time T1. To train the algorithms, each phantom was measured using a dielectric measurement device to acquire the true conductivity and permittivity. MR images were taken for each phantom, and the T1 values were measured. Then, the acquired data were tested using curve fitting, regression learning, and neural fit models to estimate the conductivity and permittivity values based on the T1 values. In particular, the regression learning algorithm based on Gaussian process regression showed high accuracy with a coefficient of determination R2 of 0.96 and 0.99 for permittivity and conductivity, respectively. The estimation of permittivity using regression learning demonstrated a lower mean error of 0.66% compared to the curve fitting method, which resulted in a mean error of 3.6%. The estimation of conductivity also showed that the regression learning approach had a lower mean error of 0.49%, whereas the curve fitting method resulted in a mean error of 6%. The findings suggest that utilizing regression learning models, specifically Gaussian process regression, can result in more accurate estimations for both permittivity and conductivity compared to other methods.
Synthesis, in vitro inhibitor screening, structure–activity relationship, and molecular dynamic simulation studies of novel thioquinoline derivatives as potent α-glucosidase inhibitors
Authors: Forozan RasaDokht , Ghomi Minoo Khalili , Iraji Aida , Montazer Mohammad Nazari , Noori Milad , Dastyafteh Navid , Mojtabavi Somayeh , Faramarzi Mohammad Ali , Sadat-Ebrahimi Seyed Esmaeil , Larijani Bagher , Javanshir Shahrzad , Mahdavi Mohammad
Published: May 2023

New series of thioquinoline structures bearing phenylacetamide 9a–p were designed, synthesized and the structure of all derivatives was confirmed using different spectroscopic techniques including FTIR, 1H-NMR, 13C-NMR, ESI–MS and elemental analysis. Next, the α-glucosidase inhibitory activities of derivatives were also determined and all the synthesized compounds (IC50 = 14.0 ± 0.6–373.85 ± 0.8 μM) were more potent than standard inhibitors acarbose (IC50 = 752.0 ± 2.0 μM) against α-glucosidase. Structure–activity relationships (SARs) were rationalized by analyzing the substituents effects and it was shown that mostly, electron-donating groups at the R position are more favorable compared to the electron-withdrawing group. Kinetic studies of the most potent derivative, 9m, carrying 2,6-dimethylphenyl exhibited a competitive mode of inhibition with Ki value of 18.0 µM. Furthermore, based on the molecular dynamic studies, compound 9m depicted noticeable interactions with the α-glucosidase active site via several H-bound, hydrophobic and hydrophilic interactions. These interactions cause interfering catalytic potential which significantly decreased the α-glucosidase activity.
Methanol fixation is the method of choice for droplet-based single-cell transcriptomics of neural cells
Authors: Gutiérrez-Franco Ana , Ake Franz , Hassan Mohamed N. , Cayuela Natalie Chaves , Mularoni Loris , Plass Mireya
Published: May 2023

The main critical step in single-cell transcriptomics is sample preparation. Several methods have been developed to preserve cells after dissociation to uncouple sample handling from library preparation. Yet, the suitability of these methods depends on the cell types to be processed. In this project, we perform a systematic comparison of preservation methods for droplet-based single-cell RNA-seq on neural and glial cells derived from induced pluripotent stem cells. Our results show that while DMSO provides the highest cell quality in terms of RNA molecules and genes detected per cell, it strongly affects the cellular composition and induces the expression of stress and apoptosis genes. In contrast, methanol fixed samples display a cellular composition similar to fresh samples and provide a good cell quality and little expression biases. Taken together, our results show that methanol fixation is the method of choice for performing droplet-based single-cell transcriptomics experiments on neural cell populations.