bluuebunny/crossref_metadata_2025 huggingface dataset:
Organic matter degradation causes enrichment of organic pollutants in hadal sediments
Authors: Sobek Anna , Abel Sebastian , Sanei Hamed , Bonaglia Stefano , Li Zhe , Horlitz Gisela , Rudra Arka , Oguri Kazumasa , Glud Ronnie N.
Published: April 2023

Burial of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) in deep-sea sediments contributes to 60% of their historical emissions. Yet, empirical data on their occurrence in the deep-ocean is scarce. Estimates of the deep-ocean POP sink are therefore uncertain. Hadal trenches, representing the deepest part of the ocean, are hotspots for organic carbon burial and decomposition. POPs favorably partition to organic carbon, making trenches likely significant sinks for contaminants. Here we show that PCBs occur in both hadal (7720–8085 m) and non-hadal (2560–4050 m) sediment in the Atacama Trench. PCB concentrations normalized to sediment dry weight were similar across sites while those normalized to sediment organic carbon increased exponentially as the inert organic carbon fraction of the sediment increased in degraded hadal sediments. We suggest that the unique deposition dynamics and elevated turnover of organic carbon in hadal trenches increase POP concentrations in the deepest places on Earth.
Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response
Authors: Ramalingam Pradeep , Gutkin Michael C. , Poulos Michael G. , Tillery Taylor , Doughty Chelsea , Winiarski Agatha , Freire Ana G. , Rafii Shahin , Redmond David , Butler Jason M.
Published: April 2023

Aging associated defects within stem cell-supportive niches contribute towards age-related decline in stem cell activity. However, mechanisms underlying age-related niche defects, and whether restoring niche function can improve stem cell fitness, remain unclear. Here, we sought to determine whether aged blood stem cell function can be restored by rejuvenating their supportive niches within the bone marrow (BM). We identify Netrin-1 as a critical regulator of BM niche cell aging. Niche-specific deletion of Netrin-1 induces premature aging phenotypes within the BM microenvironment, while supplementation of aged mice with Netrin-1 rejuvenates aged niche cells and restores competitive fitness of aged blood stem cells to youthful levels. We show that Netrin-1 plays an essential role in maintaining active DNA damage responses (DDR), and that aging-associated decline in niche-derived Netrin-1 results in DNA damage accumulation within the BM microenvironment. We show that Netrin-1 supplementation is sufficient to resolve DNA damage and restore regenerative potential of the aged BM niche and blood stem cells to endure serial chemotherapy regimens.
Hypoimmune anti-CD19 chimeric antigen receptor T cells provide lasting tumor control in fully immunocompetent allogeneic humanized mice
Authors: Hu Xiaomeng , Manner Karl , DeJesus Rowena , White Kathy , Gattis Corie , Ngo Priscilla , Bandoro Christopher , Tham Eleonore , Chu Elaine Y. , Young Chi , Wells Frank , Basco Ronald , Friera Annabelle , Kangeyan Divy , Beauchesne Pascal , Dowdle William E. , Deuse Tobias , Fry Terry J. , Foster Aaron E. , Schrepfer Sonja
Published: April 2023

Manufacturing autologous chimeric antigen receptor (CAR) T cell therapeutics is complex, and many patients experience treatment delays or cannot be treated at all. Although current allogeneic CAR products have the potential to overcome manufacturing bottlenecks, they are subject to immune rejection and failure to persist in the host, and thus do not provide the same level of efficacy as their autologous counterparts. Here, we aimed to develop universal allogeneic CAR T cells that evade the immune system and produce a durable response. We generated human hypoimmune (HIP) T cells with disrupted B2M, CIITA, and TRAC genes using CRISPR-Cas9 editing. In addition, CD47 and anti-CD19 CAR were expressed using lentiviral transduction. These allogeneic HIP CD19 CAR T cells were compared to allogeneic CD19 CAR T cells that only expressed the anti-CD19 CAR (allo CAR T). In vitro assays for cancer killing and exhaustion revealed no differences between allo CAR T and HIP CAR T cells, confirming that the HIP edits did not negatively affect T cell performance. Clearance of CD19+ tumors by HIP CAR T cells in immunodeficient NSG mice was comparable to that of allo CAR T cells. In fully immunocompetent humanized mice, HIP CAR T cells significantly outperformed allo CAR T cells, showed improved persistence and expansion, and provided lasting cancer clearance. Furthermore, CD47-targeting safety strategies reliably and specifically eliminated HIP CAR T cells. These findings suggest that universal allogeneic HIP CAR T cell-based therapeutics might overcome the limitations associated with poor persistence of allogeneic CAR T cells and exert durable anti-tumor responses.
High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike
Authors: Tan Timothy J. C. , Mou Zongjun , Lei Ruipeng , Ouyang Wenhao O. , Yuan Meng , Song Ge , Andrabi Raiees , Wilson Ian A. , Kieffer Collin , Dai Xinghong , Matreyek Kenneth A. , Wu Nicholas C.
Published: April 2023

Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we establish a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrates a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, we apply this method to a region in the S2 domain that includes the first heptad repeat and central helix. Our results reveal that besides K986P and V987P, several mutations simultaneously improve expression and significantly lower the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.
Modelling 30-day hospital readmission after discharge for COPD patients based on electronic health records
Authors: Li Meng , Cheng Kun , Ku Keisun , Li Junlei , Hu Hao , Ung Carolina Oi Lam
Published: April 2023

Chronic Obstructive Pulmonary Disease (COPD) is the third most common chronic disease in China with frequent exacerbations, resulting in increased hospitalization and readmission rate. COPD readmission within 30 days after discharge is an important indicator of care transitions, patient’s quality of life and disease management. Identifying risk factors and improving 30-day readmission prediction help inform appropriate interventions, reducing readmissions and financial burden. This study aimed to develop a 30-day readmission prediction model using decision tree by learning from the data extracted from the electronic health record of COPD patients in Macao. Health records data of COPD inpatients from Kiang Wu Hospital, Macao, from January 1, 2018, to December 31, 2019 were reviewed and analyzed. A total of 782 hospitalizations for AECOPD were enrolled, where the 30-day readmission rate was 26.5% (207). A balanced dataset was randomly generated, where male accounted for 69.1% and mean age was 80.73 years old. Age, length of stay, history of tobacco smoking, hemoglobin, systemic steroids use, antibiotics use and number of hospital admission due to COPD in last 12 months were found to be significant risk factors for 30-day readmission of CODP patients (P < 0.01). A data-driven decision tree-based modelling approach with Bayesian hyperparameter optimization was developed. The mean precision-recall and AUC value for the classifier were 73.85, 73.7 and 0.7506, showing a satisfying prediction performance. The number of hospital admission due to AECOPD in last 12 months, smoke status and patients’ age were the top factors for 30-day readmission in Macao population.
The association between psychosocial stress, interpersonal sensitivity, social withdrawal and psychosis relapse: a systematic review
Authors: Almuqrin A. , Georgiades A. , Mouhitzadeh K. , Rubinic P. , Mechelli A. , Tognin S.
Published: April 2023

Psychosis is associated with a high risk of relapse, with 67% of clients relapsing within one year following a first episode. In light of the high personal, social, and healthcare costs of the illness, it is paramount to understand the risk factors associated with psychosis relapse. The current systematic review aims to critically review the role of psychosocial stress in psychosis relapse in individuals with an established psychotic disorder. This review systematically searched Ovid (PsycINFO, EMBASE, MEDLINE) literature databases from inception until 28th February 2022. Sixteen studies were eligible for inclusion. Most studies found that individuals with psychosis demonstrate high levels of psychosocial stress and are more likely to be socially withdrawn compared to healthy controls or other clinical presentations. Most studies reported a statistically significant association between psychosocial stress and psychosis relapse, as well as between social withdrawal and psychosis relapse. However, no studies examined the association between high levels of interpersonal sensitivity and psychosis relapse. Individuals with psychosis tend to experience high levels of psychosocial stress and social withdrawal, and these appear to increase the risk of psychosis relapse. Due to high levels of heterogeneity within the literature, we could only conduct a narrative synthesis of the findings. Future studies would benefit from employing a meta-analytic approach.
An ancient metalloenzyme evolves through metal preference modulation
Authors: Sendra K. M. , Barwinska-Sendra A. , Mackenzie E. S. , Baslé A. , Kehl-Fie T. E. , Waldron K. J.
Published: April 2023

Evolution creates functional diversity of proteins, the essential building blocks of all biological systems. However, studies of natural proteins sampled across the tree of life and evaluated in a single experimental system are lacking. Almost half of enzymes require metals, and metalloproteins tend to optimally utilize the physicochemical properties of a specific metal co-factor. Life must adapt to changes in metal bioavailability, including those during the transition from anoxic to oxic Earth or pathogens’ exposure to nutritional immunity. These changes can challenge the ability of metalloenzymes to maintain activity, presumptively driving their evolution. Here we studied metal-preference evolution within the natural diversity of the iron/manganese superoxide dismutase (SodFM) family of reactive oxygen species scavengers. We identified and experimentally verified residues with conserved roles in determining metal preference that, when combined with an understanding of the protein’s evolutionary history, improved prediction of metal utilization across the five SodFM subfamilies defined herein. By combining phylogenetics, biochemistry and structural biology, we demonstrate that SodFM metal utilization can be evolutionarily fine tuned by sliding along a scale between perfect manganese and iron specificities. Over the history of life, SodFM metal preference has been modulated multiple independent times within different evolutionary and ecological contexts, and can be changed within short evolutionary timeframes.
Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens
Authors: Kylies Dominik , Zimmermann Marina , Haas Fabian , Schwerk Maria , Kuehl Malte , Brehler Michael , Czogalla Jan , Hernandez Lola C. , Konczalla Leonie , Okabayashi Yusuke , Menzel Julia , Edenhofer Ilka , Mezher Sam , Aypek Hande , Dumoulin Bernhard , Wu Hui , Hofmann Smilla , Kretz Oliver , Wanner Nicola , Tomas Nicola M. , Krasemann Susanne , Glatzel Markus , Kuppe Christoph , Kramann Rafael , Banjanin Bella , Schneider Rebekka K. , Urbschat Christopher , Arck Petra , Gagliani Nicola , van Zandvoort Marc , Wiech Thorsten , Grahammer Florian , Sáez Pablo J. , Wong Milagros N. , Bonn Stefan , Huber Tobias B. , Puelles Victor G.
Published: April 2023

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems1. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies.
Targeting the tumor microenvironment by liposomal Epacadostat in combination with liposomal gp100 vaccine
Authors: Tahaghoghi-Hajghorbani Sahar , Yazdani Mona , Nikpoor Amin Reza , Hatamipour Mahdi , Ajami Abolghasem , Jaafari Mahmoud Reza , Badiee Ali , Rafiei Alireza
Published: April 2023

Indoleamine-2,3-dioxygenase (IDO1) pathway has vital role in cancer immune escape and its upregulation leads to immunosuppressive environment which is associated with poor prognosis and progression in various cancers like melanoma. Previously, we showed the antitumoral efficacy of nanoliposomal form of Epacadostat (Lip-EPA), as an IDO1 inhibitor. Herein, we used Lip-EPA as a combination approach with liposomal gp100 (Lip-gp100) anti-cancer vaccine in melanoma model. Here, we showed that B16F10 tumor express IDO1 so using Lip-EPA will enhance the efficacy of vaccine therapy. The biodistribution of ICG-labelled liposomal form of EPA showed the remarkable accumulation of drug at tumor site. In an in vivo study, Lip-EPA enhanced the antitumor efficacy of Lip-gp100 in which the IDO mRNA expression was decreased (~ fourfold) in tumor samples. Also, we identified a significant increase in the number of infiltrated T lymphocytes (p < 0.0001) with enhanced in interferon gamma (IFN-γ) production (p < 0.0001). Additionally, Lip-EPA + Lip-gp100 significantly modulated intratumoral regulatory T cells which altogether resulted in the highest delay in tumor growth (TGD = 56.54%) and increased life span (ILS > 47.36%) in treated mice. Our study demonstrated that novel combination of Lip-EPA and Lip-gp100 was effective treatment with capability of being used in further clinical studies.
Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19
Authors: Fu Yu , Fang Yangyue , Gong Shuai , Xue Tao , Wang Peng , She Li , Huang Jianping
Published: April 2023

Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice. 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were predicted, which were confirmed by previous studies to be associated with SARS-CoV-2-infection. In addition, 2 new active compounds (glabrone and vestitol) and 2 new targets (PTEN and MAP3K8) were further validated by molecular docking and molecular dynamics simulations (simultaneous molecular dynamics), as well as the results showed that these active compounds bound well to COVID-19 related targets, including the main protease (Mpro), the spike protein (S-protein) and the angiotensin-converting enzyme 2 (ACE2). Overall, in this study, glabrone and vestitol from licorice were found to inhibit viral replication by inhibiting the activation of Mpro, S-protein and ACE2; related compounds in licorice may reduce the inflammatory response and inhibit apoptosis by acting on PTEN and MAP3K8. Therefore, licorice has been proposed as an effective candidate for the treatment of COVID-19 through PTEN, MAP3K8, Mpro, S-protein and ACE2.
Visualization of RNA virus infection in a marine protist with a universal biomarker
Authors: Coy Samantha R. , Utama Budi , Spurlin James W. , Kim Julia G. , Deshmukh Harshavardhan , Lwigale Peter , Nagasaki Keizo , Correa Adrienne M. S.
Published: April 2023

Half of the marine virosphere is hypothesized to be RNA viruses (kingdom Orthornavirae) that infect abundant micro-eukaryotic hosts (e.g. protists). To test this, quantitative approaches that broadly track infections in situ are needed. Here, we describe a technique—dsRNA-Immunofluorescence (dsRIF)—that uses a double-stranded RNA (dsRNA) targeting monoclonal antibody to assess host infection status based on the presence of dsRNA, a replicative intermediate of all Orthornavirae infections. We show that the dinoflagellate Heterocapsa circularisquama produces dsRIF signal ~ 1000 times above background autofluorescence when infected by the + ssRNA virus HcRNAV. dsRNA-positive virocells were detected across > 50% of the 48-h infection cycle and accumulated to represent at least 63% of the population. Photosynthetic and chromosomal integrity remained intact during peak replication, indicating HcRNAV infection does not interrupt these processes. This work validates the use of dsRIF on marine RNA viruses and their hosts, setting the stage for quantitative environmental applications that will accelerate understanding of virus-driven ecosystem impacts.
TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway
Authors: Tang Li , Guo Chengming , Li Xu , Zhang Bo , Huang Liuye
Published: April 2023

TATA-box-binding protein-associated Factor 15 (TAF15), a member of the FUS/EWS/TAF15 (FET) family, contributes to the progression of various tumours. However, the role and molecular mechanism of TAF15 in gastric cancer (GC) progression are still unknown. In this study, we found that TAF15 was significantly upregulated in GC tumour tissues and cell lines. Overexpression of TAF15 was associated with a larger tumour size, high pathologic stage and high T stage of GC. TAF15 knockdown suppressed the proliferation, migration and invasion of GC cells in vitro and inhibited the tumour growth in vivo. Additionally, TAF15 knockdown led to the significant reductions in the phosphorylation levels of RAF1, MEK and ERK1/2, while total RAF1, MEK and ERK1/2 exhibited no significant change in GC cell lines. In summary, TAF15 is overexpressed in GC tumour tissues and cell lines, and promotes cell proliferation, migration and invasion in GC via the RAF1/MEK/ERK signaling pathway, which suggests that TAF15 might be a potential molecular diagnostic marker or therapeutic target for GC.
The effect of barium and strontium on activity of glucoamylase QsGH97a from Qipengyuania seohaensis SW-135
Authors: Wu Kaijuan , Zhai Xingyu , Chen Hao , Zheng Jinfeng , Yu Zheng , Xu Xuewei , Huang Jing
Published: April 2023

Glycoside hydrolases (GHs), the enzymes that break glycosidic bonds, are ubiquitous in the ecosystem, where they perform a range of biological functions. As an interesting glycosidase family, Glycoside hydrolase family 97 (GH97) contains α-glucosidase, α-galactosidase, and glucoamylase. Only ten members of GH97 have been characterized so far. It is critical to explore novel members to elucidate the catalytic mechanism and application potential of GH97 family. In this study, a novel glucoamylase QsGH97a from Qipengyuania seohaensis SW-135 was cloned and expressed in E. coli. Sequence analysis and NMR results show that QsGH97a is classified into GH97a, and adopts inverting mechanism. The biochemical characterization indicates that QsGH97a shows the optimal activity at 50 °C and pH 8.0. Ca2+ has little effect on the catalytic activity; however, the activity can be substantially increased by 8–13 folds in the presence of Ba2+ or Sr2+. Additionally, the metal content of QsGH97a assay showed a high proportion of Sr2+. The specific metal activity was initially revealed in glucoamylases, which is not found in other members. These results imply that QsGH97a not only is a new member of GH97, but also has potential for industrial applications. Our study reveals that Ba2+ or Sr2+ may be involved in the catalytic mechanism of glucoamylase, laying the groundwork for a more complete knowledge of GH97 and its possible industrial application.
The spatiotemporal prediction method of urban population density distribution through behaviour environment interaction agent model
Authors: Yang Junyan , Shi Yi , Zheng Yi , Zhang Zhonghu
Published: April 2023

Based on the interrelationship between the built environment and spatial–temporal distribution of population density, this paper proposes a method to predict the spatial–temporal distribution of urban population density using the depth residual network model (ResNet) of neural network. This study used the time-sharing data of mobile phone users provided by the China Mobile Communications Corporation to predict the time–space sequence of the steady-state distribution of population density. Firstly, 40 prediction databases were constructed according to the characteristics of built environment and the spatial–temporal distribution of population density. Thereafter, the depth residual model ResNet was used as the basic framework to construct the behaviour–environment agent model (BEM) for model training and prediction. Finally, the average percentage error index was used to evaluate the prediction results. The results revealed that the accuracy rate of prediction results reached 76.92% in the central urban area of the verification case. The proposed method can be applied to prevent urban public safety incidents and alleviate pandemics. Moreover, this method can be practically applied to enable the construction of a “smart city” for improving the efficient allocation of urban resources and traffic mobility.
Shaping farmers’ beliefs, risk perception and adaptation response through Construct Level Theory in the southwest Iran
Authors: Yazdanpanah Masoud , Zobeidi Tahereh , Warner Laura A. , Löhr Katharina , Lamm Alexa , Sieber Stefan
Published: April 2023

Due to the severe effects of climate change on the agricultural sector, urgent action is required on the part of farmers and is, indeed, critical to reducing climate change impacts. However, reports globally revealed farmers’ engagement in climate change adaptation is still insufficient, ambivalent, and inconsistent and farmers do not consider adaptation to be urgent. Researchers have argued that this issue is rooted in psychological biases beside other factors. Therefore, the aim of this study is to evaluate how psychological distance determines climate change beliefs, risk perception and adaptation strategies among Iranian farmers. A cross-sectional paper-based survey was conducted in theDasht-e Azadegancounty of Khuzestan province in southwest Iran. The study sample consisted of 250 farmers selected through a multi-stage random sampling process. An expert panel review and a pilot study were conducted to confirm convergent validity and reliability of the scales. The results confirm that all four dimensions of psychological distance influence water management adaptation strategies and non-farm activities. Moreover, all psychological dimensions, except the temporal dimension, affect adaptation in farming management. Thus, making climate change more proximal to decision makers could be a strategic way of encouraging individuals to take adaptive actions. This study emphasizes that concepts of psychological distance can be applied to help organizations (e.g., agriculture extension services) to understand farmers’ risk perceptions and responses to climate change impacts and improve risk communication to better engage farmers in climate action.
Potential role of LPAR5 gene in prognosis and immunity of thyroid papillary carcinoma and pan-cancer
Authors: Zhang Ben , Zhang Lixi , Qi Peng , Pang Renzhu , Wang Ziming , Liu Xuyao , Shi Qi , Zhang Qiang
Published: April 2023

Papillary carcinomas account for the largest proportion of thyroid cancers, with papillary thyroid carcinoma (PTC) being prone to early lymph node metastasis. Some studies have confirmed that LPAR5 can promote the progression of PTC, but immune-related analyses of LPAR5 and PTC have not been widely discussed. This study aimed to determine the role of LPAR5 in PTC prognosis and immunity. We will further explore the role of LPAR5 in 33 different tumor types. Regarding PTC, we analyzed the effect of LPAR5 expression on overall survival (OS). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Immune-related analyses of immune checkpoints (ICPs) and immune cell infiltration were also performed. For pan-cancer, R packages were used to analyze prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), and immune cell infiltration. Analysis of tumor microenvironment (TME) and ICPs was performed using Sangerbox (http://vip.sangerbox.com/home.html). The TISIDB database (http://cis.hku.hk/TISIDB/index.php) was used to identify immune and molecular subtypes. LPAR5 expression is associated with PTC prognosis and immunity as well as various human tumors. LPAR5 may be a potential biomarker for multiple malignancies and may provide a new target for cancer immunotherapy.
CaMKII regulates the proteins TPM1 and MYOM2 and promotes diacetylmorphine-induced abnormal cardiac rhythms
Authors: Ji Min , Su Liping , Liu Li , Zhuang Mengjie , Xiao Jinling , Guan Yaling , Zhu Sensen , Ma Lijuan , Pu Hongwei
Published: April 2023

Although opioids are necessary for the treatment of acute pain, cancer pain, and palliative care, opioid abuse is a serious threat to society. Heroin (Diacetylmorphine) is the most commonly abused opioid, and it can have a variety of effects on the body's tissues and organs, including the well-known gastrointestinal depression and respiratory depression; however, there is little known about the effects of diacetylmorphine on cardiac damage. Here, we demonstrate that diacetylmorphine induces abnormal electrocardiographic changes in rats and causes damage to cardiomyocytes in vitro by an underlying mechanism of increased autophosphorylation of CaMKII and concomitant regulation of myocardial contractile protein TPM1 and MYOM2 protein expression. The CaMKII inhibitor KN-93 was first tested to rescue the toxic effects of heroin on cardiomyocytes in vitro and the abnormal ECG changes caused by heroin in SD rats, followed by the TMT relative quantitative protein technique to analyze the proteome changes. Diacetylmorphine causes increased phosphorylation at the CaMKII Thr287 site in myocardium, resulting in increased autophosphorylation of CaMKII and subsequent alterations in myocardial contractile proteins, leading to myocardial rhythm abnormalities. These findings provide a theoretical basis for the treatment and prevention of patients with arrhythmias caused by diacetylmorphine inhalation and injection.
Bilateral increase in MEG planar gradients prior to saccade onset
Authors: Fabius Jasper H. , Fracasso Alessio , Deodato Michele , Melcher David , Van der Stigchel Stefan
Published: April 2023

Every time we move our eyes, the retinal locations of objects change. To distinguish the changes caused by eye movements from actual external motion of the objects, the visual system is thought to anticipate the consequences of eye movements (saccades). Single neuron recordings have indeed demonstrated changes in receptive fields before saccade onset. Although some EEG studies with human participants have also demonstrated a pre-saccadic increased potential over the hemisphere that will process a stimulus after a saccade, results have been mixed. Here, we used magnetoencephalography to investigate the timing and lateralization of visually evoked planar gradients before saccade onset. We modelled the gradients from trials with both a saccade and a stimulus as the linear combination of the gradients from two conditions with either only a saccade or only a stimulus. We reasoned that any residual gradients in the condition with both a saccade and a stimulus must be uniquely linked to visually-evoked neural activity before a saccade. We observed a widespread increase in residual planar gradients. Interestingly, this increase was bilateral, showing activity both contralateral and ipsilateral to the stimulus, i.e. over the hemisphere that would process the stimulus after saccade offset. This pattern of results is consistent with predictive pre-saccadic changes involving both the current and the future receptive fields involved in processing an attended object, well before the start of the eye movement. The active, sensorimotor coupling of vision and the oculomotor system may underlie the seamless subjective experience of stable and continuous perception.
Long-term trends of pediatric type 1 diabetes incidence in Japan before and after the COVID-19 pandemic
Authors: Matsuda Fumika , Itonaga Tomoyo , Maeda Miwako , Ihara Kenji
Published: April 2023

Type 1 diabetes incidence has increased worldwide, although the long-term trends on pediatric type 1 diabetes in Japan remain elusive. To investigate the incidence and secular trend of pediatric type 1 diabetes from 1999 to 2021, including the coronavirus disease 2019 (COVID-19) pandemic years, in Oita Prefecture, Japan. We investigated the number of newly diagnosed patients with type 1 diabetes aged < 15 years from 1999 to 2021. We surveyed hospital databases in Oita Prefecture in Japan. The type 1 diabetes incidence in children aged < 15 years increased annually by 5.3% among all children, especially in boys aged 10–14 years by 8.1%, over the past 23 years. The average incidence rate of 3.9/100,000/year was nearly consistent with the previous reports on Asian countries. No significant change was found in the increasing incidence trend of type 1 diabetes before and during the COVID-19 pandemic. The incidence of pediatric type 1 diabetes has significantly increased over the past 23 years in Oita Prefecture, Japan, which is consistent with the worldwide trend.
A cross-sectional study on the relationship between visceral adiposity index and periodontitis in different age groups
Authors: Yang Qinghua , Wang Xuming , Li Chen , Wang Xuanming
Published: April 2023

Obesity and periodontitis are significantly related, and the visceral adiposity index (VAI) is an important indicator of obesity. This study aimed to investigate the association between VAI and periodontitis. The study included participants from the 2009–2014 cycle of the National Health and Nutrition Examination Survey who received a complete periodontal exam and VAI record. Periodontitis, according to the Centers for Disease Control and Prevention-American Academy of Periodontology periodontitis case definitions, is categorized into the following: no periodontitis, moderate periodontitis, mild periodontitis, and severe periodontitis. Hierarchical analysis, multivariable logistic regression, and restricted cubic spline regression were conducted to investigate the relationship between periodontitis and VAI in adults. There was no significant relationship between VAI and the prevalence of periodontitis in all age groups (P = 0.08). Age-stratified analysis showed a significant association between periodontitis and VAI in adults aged 40–50 years (P < 0.001). After adjusting for all covariates, the association between periodontitis and VAI remained significant in the 40–50-years age group (the trend P value = 0.014). Restricted cubic spline analysis showed a non-linear relationship between VAI and periodontitis (P for non-linear = 0.002). Visceral adiposity index was significantly associated with periodontitis risk in the 40–50-year-old group, and the relationship between VAI and periodontitis risk was found to be non-linear.
Alteration of gut microbiota in wild-borne long-tailed macaques after 1-year being housed in hygienic captivity
Authors: Sawaswong Vorthon , Chanchaem Prangwalai , Kemthong Taratorn , Warit Saradee , Chaiprasert Angkana , Malaivijitnond Suchinda , Payungporn Sunchai
Published: April 2023

The wild-born long-tailed macaques (Macaca fascicularis) were recently recruited and used as breeders for the National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU), and changes in their in-depth gut microbiota profiles were investigated. The Oxford Nanopore Technology (ONT) was used to explore full-length 16S rDNA sequences of gut microbiota in animals once captured in their natural habitat and 1-year following translocation and housing in a hygienic environment at NPRCT-CU. Our findings show that the gut microbiota of macaques after 1 year of hygienic housing and programmed diets feeding was altered and reshaped. The prevalent gut bacteria such as Prevotella copri and Faecalibacterium prausnitzii were enriched after translocation, causing the lower alpha diversity. The correlation analysis revealed that Prevotella copri, Phascolarctobacterium succinatutens, and Prevotella stercorea, showed a positive correlation with each other. Significantly enriched pathways in the macaques after translocation included biosynthesis of essential amino acids, fatty acids, polyamine and butanoate. The effects of microbiota change could help macaques to harvest the energy from programmed diets and adapt their gut metabolism. The novel probiotics and microbiota engineering approach could be further developed based on the current findings and should be helpful for captive animal health care management.
Randomized design evidence of the attendance benefits of the EPA School Bus Rebate Program
Authors: Pedde Meredith , Szpiro Adam , Hirth Richard , Adar Sara D.
Published: April 2023

Approximately 25 million children ride buses to school in the United States. While school buses are the safest school transport from an accident perspective, older buses often expose students to high levels of diesel exhaust. Because these exposures can adversely impact health, which may lead to more missed school, the US Environmental Protection Agency (EPA) has spent millions of dollars to hasten the transition of school bus fleets to cleaner vehicles. Here, we leveraged the randomized allocation of the EPA’s 2012–2017 School Bus Rebate Program funding to causally assess the district attendance impacts of upgrading buses. Districts randomly selected for funding had greater attendance improvements after the lottery than unselected districts, resulting in over 350,000 estimated additional student days of attendance each year (95% confidence interval = −70,678 to 772,865) due to the use of EPA funds. Attendance improvements were greatest when the oldest buses were replaced and for districts with high ridership on applicant buses. Extrapolating our results nationwide, we expect that the replacement of all pre-2000 model year school buses would lead to more than 1.3 million additional student days of attendance per year (95% confidence interval = 247,443 to 2,406,511). Given the importance of attendance to educational success, we conclude that increasing the pace at which older, highly polluting buses are replaced positively impacts student attendance.
Topography of associations between cardiovascular risk factors and myelin loss in the ageing human brain
Authors: Trofimova Olga , Latypova Adeliya , DiDomenicantonio Giulia , Lutti Antoine , de Lange Ann-Marie G. , Kliegel Matthias , Stringhini Silvia , Marques-Vidal Pedro , Vaucher Julien , Vollenweider Peter , Strippoli Marie-Pierre F. , Preisig Martin , Kherif Ferath , Draganski Bogdan
Published: April 2023

Our knowledge of the mechanisms underlying the vulnerability of the brain’s white matter microstructure to cardiovascular risk factors (CVRFs) is still limited. We used a quantitative magnetic resonance imaging (MRI) protocol in a single centre setting to investigate the cross-sectional association between CVRFs and brain tissue properties of white matter tracts in a large community-dwelling cohort (n = 1104, age range 46–87 years). Arterial hypertension was associated with lower myelin and axonal density MRI indices, paralleled by higher extracellular water content. Obesity showed similar associations, though with myelin difference only in male participants. Associations between CVRFs and white matter microstructure were observed predominantly in limbic and prefrontal tracts. Additional genetic, lifestyle and psychiatric factors did not modulate these results, but moderate-to-vigorous physical activity was linked to higher myelin content independently of CVRFs. Our findings complement previously described CVRF-related changes in brain water diffusion properties pointing towards myelin loss and neuroinflammation rather than neurodegeneration.
A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures
Authors: Govaere Olivier , Hasoon Megan , Alexander Leigh , Cockell Simon , Tiniakos Dina , Ekstedt Mattias , Schattenberg Jörn M. , Boursier Jerome , Bugianesi Elisabetta , Ratziu Vlad ,   LITMUS Investigators, Daly Ann K. , Anstee Quentin M.
Published: April 2023

Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD. In this multicentre proteomic study, we characterize 4,730 circulating proteins in 306 patients with histologically characterized NAFLD and integrate this with transcriptomic analysis in paired liver tissue. We identify circulating proteomic signatures for active steatohepatitis and advanced fibrosis, and correlate these with hepatic transcriptomics to develop a proteo-transcriptomic signature of 31 markers. Deconvolution of this signature by single-cell RNA sequencing reveals the hepatic cell types likely to contribute to proteomic changes with disease progression. As an exemplar of use as a non-invasive diagnostic, logistic regression establishes a composite model comprising four proteins (ADAMTSL2, AKR1B10, CFHR4 and TREM2), body mass index and type 2 diabetes mellitus status, to identify at-risk steatohepatitis.
The emerging role of mega-urban regions in the sustainability of global production-consumption systems
Authors: Doran E. , Golden J. , Matus K. , Lebel L. , Timmer V. , van ‘t Zelfde M. , de Koning A.
Published: April 2023

Mega-urban regions (MURs) are important consumers or traders of resources from, or producers of wastes destined for, the global hinterlands. These roles, coupled with their concentration, clustering and centrality effects, mean MURs have a disproportionately large effect on the sustainability of global production-consumption systems (PCSs). Actions taken within MURs influence the sustainability of global PCSs, and vice versa; but that influence is complicated by complex governance intersections. Three cases are used to illustrate governance innovation in MUR-PCS interactions: industrial symbiosis in Tianjin, China; electricity production in London, UK; and the adoption of standards and labels for seafood in Bangkok, Thailand. In London and Tianjin, waste capture reduced consumption of hinterland resources, whereas in Bangkok, the aim was to improve the sustainability of resource use in coastal and marine hinterlands. We suggest an agenda for research to evaluate the potential for transferrable MUR governance innovation to enable sustainable and equitable PCSs.
Trade policy announcements can increase price volatility in global food commodity markets
Authors: Brander Michael , Bernauer Thomas , Huss Matthias
Published: April 2023

Many countries use trade policy to insulate their domestic markets from price volatility. However, there is a widespread concern that such policies—particularly export restrictions—may amplify global price volatility, adversely affecting other countries. Here, using an original dataset on trade policy announcements on wheat and maize encompassing the food price crises of 2007–2008 and 2010–2011, we show that the announcement of trade policy changes can increase global price volatility. This effect applies not only to export restrictions but also to import liberalization measures and is most pronounced when markets are tight (stocks are low). Policymakers should work towards increasing stock levels to mitigate price volatility effects of trade policy changes. When markets are tight, export restrictions and import liberalizations should be avoided.
A topological path to the formation of a quasi-planar B70 boron cluster and its dianion
Authors: Saha Pinaki , Buendía Fernando , Van Duong Long , Nguyen Minh Tho
Published: April 2023

Structures of B70 in both neutral and dianionic states were reinvestigated using genetic search, leapfrog path and DFT computations. The quasi-planar form of the B702− dianion possesses 50 π-electrons that satisfy disk aromaticity count and make it the most stable isomer.
A survey on molecular-scale learning systems with relevance to DNA computing
Authors: Nagipogu Rajiv Teja , Fu Daniel , Reif John H.
Published: April 2023

DNA computing has emerged as a promising alternative to achieve programmable behaviors in chemistry by repurposing the nucleic acid molecules into chemical hardware upon which synthetic chemical programs can be executed.
Substitution engineering of lead-free halide perovskites for photocatalytic applications assisted by machine learning
Authors: Wang Tao , Fan Shuxin , Jin Hao , Yu Yunjin , Wei Yadong
Published: April 2023

Lead-free perovskites (A3B2X9) have drawn much attention in recent years. Rather than relying solely on human cognitive abilities, machine learning technology is being employed to explore these materials comprehensively.
The selective heating effect of microwave irradiation on a binary mixture of water and polyethylene oxide: a molecular dynamics simulation approach
Authors: Chen Junhe , Warner Matthew J. , Sikora Benjamin , Kiddle Daniel , Coverdell Danielle , Allam Omar , Kohl Paul A. , Jang Seung Soon
Published: April 2023

Microwave-driven selective heating for water–PEO binary mixtures has been studied using MD simulations to elucidate the structural and dynamic responses.
Monitoring the melting behavior of boron nanoparticles using a neural network potential
Authors: Chang Xiaoya , Chu Qingzhao , Chen Dongping
Published: April 2023

A neural network potential (NNP) is proposed to examine the size-dependent melting behaviors of boron nanoparticles. The simulation results indicate that the melting mode of boron particles follows the liquid nucleation and growth theory.
Mn mixed oxide catalysts supported on Sn-doped CoAl-LDO for low-temperature NH3-SCR
Authors: Wang Hange , Chen Wen , Jin Wei , Liu Yueli
Published: April 2023

The Sn-doped MnOx(0.25)/CoSn3Al-LDO catalyst by hydrothermal and impregnation methods achieves 100% NO conversion at 120–330 °C.
A purified fraction of polysaccharides from the fruits of Lycium barbarum L. improves glucose homeostasis and intestinal barrier function in high-fat diet-fed mice
Authors: Zhou Wangting , Liu Peiyun , Xu Weiqi , Ran Linwu , Yan Yamei , Lu Lu , Zeng Xiaoxiong , Cao Youlong , Mi Jia
Published: April 2023

A purified fraction of polysaccharides obtained from the fruits of Lycium barbarum L. shaped the gut community profile and improved glucose homeostasis as well as intestinal barrier function in high-fat diet-induced diabetic mice.
Polyphenols fromPrunus mume: extraction, purification, and anticancer activity
Authors: Zhao Fengyi , Du Lanlan , Wang Jialuan , Liu Hongxia , Zhao Huifang , Lyu Lianfei , Wang Weifan , Wu Wenlong , Li Weilin
Published: April 2023

Prunus mumeis an ancient medicinal herb and food that are commonly used in Asian countries with high nutritional ingredients and biological activities.
Enrichment and detection of VEGF165 in blood samples on a microfluidic chip integrated with multifunctional units
Authors: He Xinyu , Xu Junyan , Wang Xiaoli , Ge Chuang , Li Shunbo , Wang Li , Xu Yi
Published: April 2023

A novel multifunctional microfluidic chip integrated with blood centrifugation, ATPS mixing, VEGF165 enrichment, and fluorescence detection.
Direct ink writing of PEDOT eutectogels as substrate-free dry electrodes for electromyography
Authors: Aguzin Ana , Dominguez-Alfaro Antonio , Criado-Gonzalez Miryam , Velasco-Bosom Santiago , Picchio Matías L. , Casado Nerea , Mitoudi-Vagourdi Eleni , Minari Roque J. , Malliaras George G. , Mecerreyes David
Published: April 2023

Deep Eutectic Solvents (DES) and PEDOT:PSS have been combined to create a superior class of supramolecular and conductive ionic-electronic material that present attractive application in the field of bioelectronics.
Tuning the enzyme-like activity of peptide–nanoparticle conjugates with amino acid sequences
Authors: Zhang Xiaojin , Wang Yichuan , Dai Yu , Xia Fan
Published: April 2023

Peptide–nanoparticle conjugates show hydrolase-like activity, which is tuned by amino acid sequences.
From cotton to functional flexible transparent film for printable and flexible microsupercapacitor with strong bonding interface
Authors: Zhang Wenjie , Li Bohan , Lv Ruitao , Li Huaming , Weng Yuqing , Shen Wanci , Kang Feiyu , Huang Zheng-Hong
Published: April 2023

A novel functional flexible transparent film with excellent printability, swellability, degradability, and hydroxyl groups is directly developed from natural cotton.
A high-performance “fueled” photodetector based on few-layered 2D ternary chalcogenide NiGa2S4
Authors: Serra Marco , Antonatos Nikolas , Luxa Jan , Lajaunie Luc , Albero Josep , Sabik Agata , Linhart Wojciech M. , Garcia Hermenegildo , Kudrawiec Robert , Sedmidubský David , Sofer Zdenek
Published: April 2023

The activity of “fueled” NiGa2S4/ITO photodetector is described. The presence of ethanol boosts the performances of the photodetector increasing its responsivity and spectral response.