bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging significance and therapeutic targets of ferroptosis: a potential avenue for human kidney diseases
Authors: Li Jinghan , Zheng Sujuan , Fan Yumei , Tan Ke
Published: September 2023

Kidney diseases remain one of the leading causes of human death and have placed a heavy burden on the medical system. Regulated cell death contributes to the pathology of a plethora of renal diseases. Recently, with in-depth studies into kidney diseases and cell death, a new iron-dependent cell death modality, known as ferroptosis, has been identified and has attracted considerable attention among researchers in the pathogenesis of kidney diseases and therapeutics to treat them. The majority of studies suggest that ferroptosis plays an important role in the pathologies of multiple kidney diseases, such as acute kidney injury (AKI), chronic kidney disease, and renal cell carcinoma. In this review, we summarize recently identified regulatory molecular mechanisms of ferroptosis, discuss ferroptosis pathways and mechanisms of action in various kidney diseases, and describe the protective effect of ferroptosis inhibitors against kidney diseases, especially AKI. By summarizing the prominent roles of ferroptosis in different kidney diseases and the progress made in studying ferroptosis, we provide new directions and strategies for future research on kidney diseases. In summary, ferroptotic factors are potential targets for therapeutic intervention to alleviate different kidney diseases, and targeting them may lead to new treatments for patients with kidney diseases.
Methylation of BRD4 by PRMT1 regulates BRD4 phosphorylation and promotes ovarian cancer invasion
Authors: Liu Yi , Liu Hejing , Ye Miaomiao , Jiang Mengying , Chen Xin , Song Gendi , Ji Huihui , Wang Zhi-wei , Zhu Xueqiong
Published: September 2023

Bromodomain-containing protein 4 (BRD4), the major component of bromodomain and extra-terminal domain (BET) protein family, has important functions in early embryonic development and cancer development. However, the posttranslational modification of BRD4 is not well understood. Multiple approaches were used to explore the mechanism of PRMT1-mediated BRD4 methylation and to determine the biological functions of BRD4 and PRMT1 in ovarian cancer. Here we report that BRD4 is asymmetrically methylated at R179/181/183 by PRMT1, which is antagonized by the Jumonji-family demethylase, JMJD6. PRMT1 is overexpressed in ovarian cancer tissue and is a potential marker for poor prognosis in ovarian cancer patients. Silencing of PRMT1 inhibited ovarian cancer proliferation, migration, and invasion in vivo and in vitro. PRMT1-mediated BRD4 methylation was found to promote BRD4 phosphorylation. Compared to BRD4 wild-type (WT) cells, BRD4 R179/181/183K mutant-expressing cells showed reduced ovarian cancer metastasis. BRD4 arginine methylation is also associated with TGF-β signaling. Our results indicate that arginine methylation of BRD4 by PRMT1 is involved in ovarian cancer tumorigenesis. Targeting PRMT1-mediated arginine methylation may provide a novel diagnostic target and an effective therapeutic strategy for ovarian cancer treatment.
In vivo self-assembly and delivery of VEGFR2 siRNA-encapsulated small extracellular vesicles for lung metastatic osteosarcoma therapy
Authors: Yu Lingfeng , Fan Gentao , Wang Qingyan , Zhu Yan , Zhu Hao , Chang Jiang , Wang Zhen , Zhan Shoubin , Hua Xianming , She Diankun , Huang Jianhao , Wang Yicun , Zhao Jianning , Zhang Chen-Yu , Chen Xi , Zhou Guangxin
Published: September 2023

The prognosis of lung metastatic osteosarcoma (OS) remains disappointing. siRNA-based gene silencing of VEGFR2 is a promising treatment strategy for lung metastatic OS, but there is a lack of safe and efficient delivery systems to encapsulate siRNAs for in vivo administration. This study presented a synthetic biological strategy that remolds the host liver with synthesized genetic circuits for efficient in vivo VEGFR2 siRNA delivery. After being taken-up by hepatocytes, the genetic circuit (in the form of a DNA plasmid) reprogrammed the liver to drive the autonomous intrahepatic assembly and encapsulation of VEGFR2 siRNAs into secretory small extracellular vesicles (sEVs), thus allowing for the transport of self-assembled VEGFR2 siRNAs towards the lung. The results showed that our strategy was superior to the positive medicine (Apatinib) for OS lung metastasis in terms of therapeutic efficacy and toxic adverse effects and may provide a feasible and viable therapeutic solution for lung metastatic OS.
Comprehensive proteomics and meta-analysis of COVID-19 host response
Authors: Babačić Haris , Christ Wanda , Araújo José Eduardo , Mermelekas Georgios , Sharma Nidhi , Tynell Janne , García Marina , Varnaite Renata , Asgeirsson Hilmir , Glans Hedvig , Lehtiö Janne , Gredmark-Russ Sara , Klingström Jonas , Pernemalm Maria
Published: September 2023

COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.
Telomerase RNA-based aptamers restore defective myelopoiesis in congenital neutropenic syndromes
Authors: Martínez-Balsalobre Elena , García-Castillo Jesús , García-Moreno Diana , Naranjo-Sánchez Elena , Fernández-Lajarín Miriam , Blasco María A. , Alcaraz-Pérez Francisca , Mulero Victoriano , Cayuela María L.
Published: September 2023

Telomerase RNA (TERC) has a noncanonical function in myelopoiesis binding to a consensus DNA binding sequence and attracting RNA polymerase II (RNA Pol II), thus facilitating myeloid gene expression. The CR4/CR5 domain of TERC is known to play this role, since a mutation of this domain found in dyskeratosis congenita (DC) patients decreases its affinity for RNA Pol II, impairing its myelopoietic activity as a result. In this study, we report that two aptamers, short single-stranded oligonucleotides, based on the CR4/CR5 domain were able to increase myelopoiesis without affecting erythropoiesis in zebrafish. Mechanistically, the aptamers functioned as full terc; that is, they increased the expression of master myeloid genes, independently of endogenous terc, by interacting with RNA Pol II and with the terc-binding sequences of the regulatory regions of such genes, enforcing their transcription. Importantly, aptamers harboring the CR4/CR5 mutation that was found in DC patients failed to perform all these functions. The therapeutic potential of the aptamers for treating neutropenia was demonstrated in several preclinical models. The findings of this study have identified two potential therapeutic agents for DC and other neutropenic patients.
CREB1-driven CXCR4hi neutrophils promote skin inflammation in mouse models and human patients
Authors: Chen Jiaoling , Bai Yaxing , Xue Ke , Li Zhiguo , Zhu Zhenlai , Li Qingyang , Yu Chen , Li Bing , Shen Shengxian , Qiao Pei , Li Caixia , Luo Yixin , Qiao Hongjiang , Dang Erle , Yin Wen , Gudjonsson Johann E. , Wang Gang , Shao Shuai
Published: September 2023

Neutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4hi neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity. Compared to CXCR4lo neutrophils, CXCR4hi neutrophils have enhanced NETs formation, phagocytic function, neutrophil degranulation, and overexpression of pro-inflammatory cytokines and chemokines in vitro. This is accompanied by a metabolic shift in CXCR4hi neutrophils toward glycolysis and lactate release, thereby promoting vascular permeability and remodeling. CXCR4 expression in neutrophils is dependent on CREB1, a transcription factor activated by TNF and CXCL12, and regulated by de novo synthesis. In vivo, CXCR4hi neutrophil infiltration amplifies skin inflammation, whereas blockade of CXCR4hi neutrophils through CXCR4 or CXCL12 inhibition leads to suppression of immune responses. In this work, our study identifies CREB1 as a critical regulator of CXCR4hi neutrophil development and characterizes the contribution of CXCR4hi neutrophils to vascular remodeling and inflammatory responses in skin.
Altered ubiquitin signaling induces Alzheimer’s disease-like hallmarks in a three-dimensional human neural cell culture model
Authors: Maniv Inbal , Sarji Mahasen , Bdarneh Anwar , Feldman Alona , Ankawa Roi , Koren Elle , Magid-Gold Inbar , Reis Noa , Soteriou Despina , Salomon-Zimri Shiran , Lavy Tali , Kesselman Ellina , Koifman Naama , Kurz Thimo , Kleifeld Oded , Michaelson Daniel , van Leeuwen Fred W. , Verheijen Bert M. , Fuchs Yaron , Glickman Michael H.
Published: September 2023

Alzheimer’s disease (AD) is characterized by toxic protein accumulation in the brain. Ubiquitination is essential for protein clearance in cells, making altered ubiquitin signaling crucial in AD development. A defective variant, ubiquitin B + 1 (UBB+1), created by a non-hereditary RNA frameshift mutation, is found in all AD patient brains post-mortem. We now detect UBB+1in human brains during early AD stages. Our study employs a 3D neural culture platform derived from human neural progenitors, demonstrating that UBB+1alone induces extracellular amyloid-β (Aβ) deposits and insoluble hyperphosphorylated tau aggregates. UBB+1competes with ubiquitin for binding to the deubiquitinating enzyme UCHL1, leading to elevated levels of amyloid precursor protein (APP), secreted Aβ peptides, and Aβ build-up. Crucially, silencing UBB+1expression impedes the emergence of AD hallmarks in this model system. Our findings highlight the significance of ubiquitin signalling as a variable contributing to AD pathology and present a nonclinical platform for testing potential therapeutics.
Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition
Authors: Petrosius Valdemaras , Aragon-Fernandez Pedro , Üresin Nil , Kovacs Gergo , Phlairaharn Teeradon , Furtwängler Benjamin , Op De Beeck Jeff , Skovbakke Sarah L. , Goletz Steffen , Thomsen Simon Francis , Keller Ulrich auf dem , Natarajan Kedar N. , Porse Bo T. , Schoof Erwin M.
Published: September 2023

Single-cell resolution analysis of complex biological tissues is fundamental to capture cell-state heterogeneity and distinct cellular signaling patterns that remain obscured with population-based techniques. The limited amount of material encapsulated in a single cell however, raises significant technical challenges to molecular profiling. Due to extensive optimization efforts, single-cell proteomics by Mass Spectrometry (scp-MS) has emerged as a powerful tool to facilitate proteome profiling from ultra-low amounts of input, although further development is needed to realize its full potential. To this end, we carry out comprehensive analysis of orbitrap-based data-independent acquisition (DIA) for limited material proteomics. Notably, we find a fundamental difference between optimal DIA methods for high- and low-load samples. We further improve our low-input DIA method by relying on high-resolution MS1 quantification, thus enhancing sensitivity by more efficiently utilizing available mass analyzer time. With our ultra-low input tailored DIA method, we are able to accommodate long injection times and high resolution, while keeping the scan cycle time low enough to ensure robust quantification. Finally, we demonstrate the capability of our approach by profiling mouse embryonic stem cell culture conditions, showcasing heterogeneity in global proteomes and highlighting distinct differences in key metabolic enzyme expression in distinct cell subclusters.
mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge
Authors: Hou Fujun , Zhang Yuntao , Liu Xiaohu , Murad Yanal M , Xu Jiang , Yu Zhibin , Hua Xianwu , Song Yingying , Ding Jun , Huang Hongwei , Zhao Ronghua , Jia William , Yang Xiaoming
Published: September 2023

The recent outbreaks of mpox have raised concerns over the need for effective vaccines. However, the current approved vaccines have either been associated with safety concerns or are in limited supply. mRNA vaccines, which have shown high efficacy and safety against SARS-CoV-2 infection, are a promising alternative. In this study, three mRNA vaccines are developed that encode monkeypox virus (MPXV) proteins A35R and M1R, including A35R extracellular domain -M1R fusions (VGPox 1 and VGPox 2) and a mixture of encapsulated full-length mRNAs for A35R and M1R (VGPox 3). All three vaccines induce early anti-A35R antibodies in female Balb/c mice, but only VGPox 1 and 2 generate detectable levels of anti-M1R antibodies at day 7 after vaccination. However, all three mRNA vaccine groups completely protect mice from a lethal dose of vaccinia virus (VACV) challenge. A single dose of VGPox 1, 2, and 3 provide protection against the lethal viral challenge within 7 days post-vaccination. Long-term immunity and protection were also observed in all three candidates. Additionally, VGPox 2 provided better passive protection. These results suggest that the VGPox series vaccines enhance immunogenicity and can be a viable alternative to current whole-virus vaccines to defend against mpox.
East Asian summer rainfall stimulated by subseasonal Indian monsoonal heating
Authors: Li Shixue , Sato Tomonori , Nakamura Tetsu , Guo Wenkai
Published: September 2023

The responses of the East Asian summer monsoon (EASM) to the Indian summer monsoon (ISM) have been the subject of extensive investigation. Nevertheless, it remains uncertain whether the ISM can serve as a predictor for the EASM. Here, on the basis of both observations and a large-ensemble climate model experiment, we show that the subseasonal variability of abnormal diabatic heating over India enhances precipitation over central East China, the Korean Peninsula, and southern Japan in June. ISM heating triggers Rossby wave propagation along the subtropical jet, promoting southerly winds over East Asia. The southerly winds helps steer anomalous mid-tropospheric warm advection and lower-tropospheric moisture advection toward East Asia, providing conditions preferential for rainband formation. Cluster analysis shows that, depending on jet structures, ISM heating can serve as a trigger as well as a reinforcer of the rainband.
Efficient combinatorial optimization by quantum-inspired parallel annealing in analogue memristor crossbar
Authors: Jiang Mingrui , Shan Keyi , He Chengping , Li Can
Published: September 2023

Combinatorial optimization problems are prevalent in various fields, but obtaining exact solutions remains challenging due to the combinatorial explosion with increasing problem size. Special-purpose hardware such as Ising machines, particularly memristor-based analog Ising machines, have emerged as promising solutions. However, existing simulate-annealing-based implementations have not fully exploited the inherent parallelism and analog storage/processing features of memristor crossbar arrays. This work proposes a quantum-inspired parallel annealing method that enables full parallelism and improves solution quality, resulting in significant speed and energy improvement when implemented in analog memristor crossbars. We experimentally solved tasks, including unweighted and weighted Max-Cut and traveling salesman problem, using our integrated memristor chip. The quantum-inspired parallel annealing method implemented in memristor-based hardware has demonstrated significant improvements in time- and energy-efficiency compared to previously reported simulated annealing and Ising machine implemented on other technologies. This is because our approach effectively exploits the natural parallelism, analog conductance states, and all-to-all connection provided by memristor technology, promising its potential for solving complex optimization problems with greater efficiency.
Alteration of perivascular reflectivity on optical coherence tomography of branched retinal vein obstruction
Authors: Hwang Bo-Een , Kim Joo-Young , Kim Rae-Young , Kim Mirinae , Park Young-Geun , Park Young-Hoon
Published: September 2023

This study aimed to evaluate perivascular reflectivity in patients with branched retinal vascular obstruction (BRVO) using en-face optical coherence tomography (OCT). The study retrospectively analyzed 45 patients with recurrent BRVO, 30 with indolent BRVO, and 45 age- and sex-matched controls. Using a 3.0 × 3.0-mm deep capillary plexus slab on macular scans, OCT angiography (OCTA) and structural en-face OCT scans were divided into four quadrants. Obstructive quadrants of OCTA scans were binarized using a threshold value of mean + 2 standard deviation. The selected area of high signal strength (HSS) was applied to the structural en-face OCT scans, and the corrected mean perivascular reflectivity was calculated as the mean reflectivity on the HSS area/overall en-face OCT mean reflectivity. The same procedure was performed in the quadrants of the matched controls. Regression analysis was conducted on several factors possibly associated with corrected perivascular reflectivity. The perivascular reflectivity in the obstructive BRVO quadrant was significantly higher than in the indolent BRVO and control quadrants (P = 0.009, P = 0.003). Both univariate and multivariate regression analyses showed a significant correlation between the average number of intravitreal injections (anti-vascular endothelial growth factor or dexamethasone implant) per year and refractive errors and image binarization threshold and perivascular reflectivity (P = 0.011, 0.013, < 0.001/univariate; 0.007, 0.041, 0.005/multivariate, respectively). En-face OCT scans of the deep capillary plexus slab revealed higher perivascular reflectivity in recurrent BRVO eyes than in indolent BRVO and control eyes. The results also indicate a remarkable correlation between perivascular reflectivity and the average number of intravitreal injections, suggesting a link to recurrence rates.
Frugal day-ahead forecasting of multiple local electricity loads by aggregating adaptive models
Authors: Lambert Guillaume , Hamrouche Bachir , de Vilmarest Joseph
Published: September 2023

This paper focuses on day-ahead electricity load forecasting for substations of the distribution network in France; therefore, the corresponding problem lies between the instability of a single consumption and the stability of a countrywide total demand. Moreover, this problem requires to forecast the loads of over one thousand substations; consequently, it belongs to the field of multiple time series forecasting. To that end, the paper applies an adaptive methodology that provided excellent results at a national scale; the idea is to combine generalized additive models with state-space representations. However, extending this methodology to the prediction of over a thousand time series raises a computational issue. It is solved by developing a frugal variant that reduces the number of estimated parameters: forecasting models are estimated only for a few time series and transfer learning is achieved by relying on aggregation of experts. This approach yields a reduction of computational needs and their associated emissions. Several variants are built, corresponding to different levels of parameter transfer, to find the best trade-off between accuracy and frugality. The selected method achieves competitive results compared to individual models. Finally, the paper highlights the interpretability of the models, which is important for operational applications.
T cell exhaustion is associated with cognitive status and amyloid accumulation in Alzheimer’s disease
Authors: Grayson Jason M. , Short Samantha M. , Lee C. Jiah , Park Nuri , Marsac Caitlyn , Sette Alessandro , Lindestam Arlehamn Cecillia S. , Leng Xiaoyan I. , Lockhart Samuel N. , Craft Suzanne
Published: September 2023

Studies over the last 100 years have suggested a link between inflammation, infectious disease, and Alzheimer’s Disease (AD). Understanding how the immune system changes during the development of AD may facilitate new treatments. Here, we studied an aging cohort who had been assessed for AD pathology with amyloid positron emission tomography and cognitive testing, and conducted high dimensional flow cytometry on peripheral blood mononuclear and cerebrospinal fluid cells. Participants were assigned a classification of being amyloid negative cognitively normal, amyloid positive cognitively normal (APCN), or amyloid positive mild cognitive impairment (APMCI), an early stage of AD. We observed major alterations in the peripheral innate immune system including increased myeloid and plasmacytoid dendritic cells in the blood of APMCI participants. When the adaptive immune system was examined, amyloid positive participants, regardless of cognitive status, had increased CD3+ T cells. Further analyses of CD4+ and CD8+ T cells revealed that APMCI participants had an increase in more differentiated phenotype T cells, such as effector memory and effector memory CD45RA expressing (TEMRA), compared to those with normal cognition. When T cell function was measured, we observed that T cells from APCN participants had increased IFNγ+GzB- producing cells compared to the other participants. In contrast, we demonstrate that APMCI participants had a major increase in T cells that lacked cytokine production following restimulation and expressed increased levels of PD-1 and Tox, suggesting these are exhausted cells. Rejuvenation of these cells may provide a potential treatment for AD.
Periodic, n-soliton and variable separation solutions for an extended (3+1)-dimensional KP-Boussinesq equation
Authors: Shao Chuanlin , Yang Lu , Yan Yongsheng , Wu Jingyu , Zhu Minting , Li Lingfei
Published: September 2023

An extended (3+1)-dimensional Kadomtsev–Petviashvili–Boussinesq equation is studied in this paper to construct periodic solution, n-soliton solution and folded localized excitation. Firstly, with the help of the Hirota’s bilinear method and ansatz, some periodic solutions have been derived. Secondly, taking Burgers equation as an auxiliary function, we have obtained n-soliton solution and n-shock wave. Lastly, we present a new variable separation method for (3+1)-dimensional and higher dimensional models, and use it to derive localized excitation solutions. To be specific, we have constructed various novel structures and discussed the interaction dynamics of folded solitary waves. Compared with the other methods, the variable separation solutions obtained in this paper not only directly give the analytical form of the solution u instead of its potential $$u_y$$

u
y

, but also provide us a straightforward approach to construct localized excitation for higher order dimensional nonlinear partial differential equation.
Multidimensional computational study to understand non-coding RNA interactions in breast cancer metastasis
Authors: Chakraborty Sohini , Banerjee Satarupa
Published: September 2023

Metastasis is a major breast cancer hallmark due to which tumor cells tend to relocate to regional or distant organs from their organ of origin. This study is aimed to decipher the interaction among 113 differentially expressed genes, interacting non-coding RNAs and drugs (614 miRNAs, 220 lncRNAs and 3241 interacting drugs) associated with metastasis in breast cancer. For an extensive understanding of genetic interactions in the diseased state, a backbone gene co-expression network was constructed. Further, the mRNA–miRNA–lncRNA–drug interaction network was constructed to identify the top hub RNAs, significant cliques and topological parameters associated with differentially expressed genes. Then, the mRNAs from the top two subnetworks constructed are considered for transcription factor (TF) analysis. 39 interacting miRNAs and 1641 corresponding TFs for the eight mRNAs from the subnetworks are also utilized to construct an mRNA–miRNA–TF interaction network. TF analysis revealed two TFs (EST1 and SP1) from the cliques to be significant. TCGA expression analysis of miRNAs and lncRNAs as well as subclass-based and promoter methylation-based expression, oncoprint and survival analysis of the mRNAs are also done. Finally, functional enrichment of mRNAs is also performed. Significant cliques identified in the study can be utilized for identification of newer therapeutic interventions for breast cancer. This work will also help to gain a deeper insight into the complicated molecular intricacies to reveal the potential biomarkers involved with breast cancer progression in future.
Impact of red blood cell distribution width–albumin ratio on prognosis of patients with CKD
Authors: Kimura Hiroshi , Tanaka Kenichi , Saito Hirotaka , Iwasaki Tsuyoshi , Kazama Sakumi , Shimabukuro Michio , Asahi Koichi , Watanabe Tsuyoshi , Kazama Junichiro James
Published: September 2023

The red blood cell distribution width–albumin ratio (RAR) is a prognostic factor for adverse outcomes in various populations. However, whether RAR is associated with renal outcomes remains unclear. Therefore, we aimed to investigate the impact of RAR on the prognosis in patients with chronic kidney disease (CKD). We conducted a retrospective cohort study using 997 CKD patients who were enrolled in the Fukushima Cohort Study. Patients were categorized into tertiles (T1-3) according to the baseline RAR. The associations of RAR with end-stage kidney disease (ESKD) were assessed using Kaplan–Meier curves and multivariable cox regression analyses. Receiver operating characteristic (ROC) curves were performed to test whether significant differences were present between red cell distribution width (RDW) and RAR. The median age was 66, 57% were men, the median eGFR was 47.8 ml/min/1.73 m2, and the median value of RAR was 3.5. The higher RAR group showed an increased risk for ESKD in the Kaplan–Meier curve analysis. Compared to the lowest RAR group, higher RAR groups had a higher risk of ESKD (hazard ratio [HR] 1.37, 95% CI 0.68–2.78 and 2.92, 95% CI 1.44–5.94) for T2 and T3 groups, respectively. ROC curve analysis proved that the discriminating ability of RAR for ESKD was superior to RDW. A higher RAR value was associated with worse renal outcomes in patients with CKD. RAR could be a convenient and useful prognostic marker for renal prognosis.
SL-scan identifies synthetic lethal interactions in cancer using metabolic networks
Authors: Zangene Ehsan , Marashi Sayed-Amir , Montazeri Hesam
Published: September 2023

Exploiting synthetic lethality is a promising strategy for developing targeted cancer therapies. However, identifying clinically significant synthetic lethal (SL) interactions among a large number of gene combinations is a challenging computational task. In this study, we developed the SL-scan pipeline based on metabolic network modeling to discover SL interaction. The SL-scan pipeline identifies the association between simulated Flux Balance Analysis knockout scores and mutation data across cancer cell lines and predicts putative SL interactions. We assessed the concordance of the SL pairs predicted by SL-scan with those of obtained from analysis of the CRISPR, shRNA, and PRISM datasets. Our results demonstrate that the SL-scan pipeline outperformed existing SL prediction approaches based on metabolic networks in identifying SL pairs in various cancers. This study emphasizes the importance of integrating multiple data sources, particularly mutation data, when identifying SL pairs for targeted cancer therapies. The findings of this study may lead to the development of novel targeted cancer therapies.
Drug-induced social connection: both MDMA and methamphetamine increase feelings of connectedness during controlled dyadic conversations
Authors: Molla Hanna , Lee Royce , Lyubomirsky Sonja , de Wit Harriet
Published: September 2023

MDMA is a stimulant-like drug with distinctive empathogenic effects. Its pro-social effects, such as feelings of connectedness, may contribute to both its popularity as a recreational drug and its apparent value as an adjunct to psychotherapy. However, little is known about the behavioral processes by which MDMA affects social interactions. This investigation examined the effects of MDMA (100 mg versus placebo; N = 18) on feelings of connectedness with an unfamiliar partner during a semi-structured casual conversation. A separate study examined the effects of a prototypic stimulant methamphetamine (MA; 20 mg versus placebo; N = 19) to determine the pharmacological specificity of effects. Oxytocin levels were obtained in both studies. Compared to placebo, both MDMA and MA increased feelings of connection with the conversation partners. Both MDMA and MA increased oxytocin levels, but oxytocin levels were correlated with feeling closer to the partner only after MDMA. These findings demonstrate an important new dimension of the pro-social effects of MDMA, its ability to increase feelings of connectedness during casual conversations between two individuals. Surprisingly, MA had a similar effect. The findings extend our knowledge of the social effects of these drugs, and illustrate a sensitive method for assessing pro-social effects during in-person dyadic encounters.
ANGPTL2 promotes immune checkpoint inhibitor-related murine autoimmune myocarditis
Authors: Horiguchi Haruki , Kadomatsu Tsuyoshi , Yamashita Tomoya , Yumoto Shinsei , Terada Kazutoyo , Sato Michio , Morinaga Jun , Miyata Keishi , Oike Yuichi
Published: September 2023

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy advances rapidly in the clinic. Despite their therapeutic benefits, ICIs can cause clinically significant immune-related adverse events (irAEs), including myocarditis. However, the cellular and molecular mechanisms regulating irAE remain unclear. Here, we investigate the function of Angiopoietin-like protein 2 (ANGPTL2), a potential inflammatory mediator, in a mouse model of ICI-related autoimmune myocarditis. ANGPTL2 deficiency attenuates autoimmune inflammation in these mice, an outcome associated with decreased numbers of T cells and macrophages. We also show that cardiac fibroblasts express abundant ANGPTL2. Importantly, cardiac myofibroblast-derived ANGPTL2 enhances expression of chemoattractants via the NF-κB pathway, accelerating T cell recruitment into heart tissues. Our findings suggest an immunostimulatory function for ANGPTL2 in the context of ICI-related autoimmune inflammation and highlight the pathophysiological significance of ANGPTL2-mediated cardiac myofibroblast/immune cell crosstalk in enhancing autoimmune responses. These findings overall provide insight into mechanisms regulating irAEs.
Intrinsically disordered regions in TRPV2 mediate protein-protein interactions
Authors: Sanganna Gari Raghavendar R. , Tagiltsev Grigory , Pumroy Ruth A. , Jiang Yining , Blackledge Martin , Moiseenkova-Bell Vera Y. , Scheuring Simon
Published: September 2023

Transient receptor potential (TRP) ion channels are gated by diverse intra- and extracellular stimuli leading to cation inflow (Na+, Ca2+) regulating many cellular processes and initiating organismic somatosensation. Structures of most TRP channels have been solved. However, structural and sequence analysis showed that ~30% of the TRP channel sequences, mainly the N- and C-termini, are intrinsically disordered regions (IDRs). Unfortunately, very little is known about IDR ‘structure’, dynamics and function, though it has been shown that they are essential for native channel function. Here, we imaged TRPV2 channels in membranes using high-speed atomic force microscopy (HS-AFM). The dynamic single molecule imaging capability of HS-AFM allowed us to visualize IDRs and revealed that N-terminal IDRs were involved in intermolecular interactions. Our work provides evidence about the ‘structure’ of the TRPV2 IDRs, and that the IDRs may mediate protein-protein interactions.
Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome
Authors: Chan Chun-Ho , Lam Yin-Yu , Wong Nicodemus , Geng Lin , Zhang Jilin , Ahola Virpi , Zare Aman , Li Ronald Adolphus , Lanner Fredrik , Keung Wendy , Cheung Yiu-Fai
Published: September 2023

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Ventricular dysfunction and cardiac arrhythmias are well-documented complications in patients with repaired TOF. Whether intrinsic abnormalities exist in TOF cardiomyocytes is unknown. We establish human induced pluripotent stem cells (hiPSCs) from TOF patients with and without DiGeorge (DG) syndrome, the latter being the most commonly associated syndromal association of TOF. TOF-DG hiPSC-derived cardiomyocytes (hiPSC-CMs) show impaired ventricular specification, downregulated cardiac gene expression and upregulated neural gene expression. Transcriptomic profiling of the in vitro cardiac progenitors reveals early bifurcation, as marked by ectopic RGS13 expression, in the trajectory of TOF-DG-hiPSC cardiac differentiation. Functional assessments further reveal increased arrhythmogenicity in TOF-DG-hiPSC-CMs. These findings are found only in the TOF-DG but not TOF-with no DG (ND) patient-derived hiPSC-CMs and cardiac progenitors (CPs), which have implications on the worse clinical outcomes of TOF-DG patients.
Designing stimuli-responsive upconversion nanoparticles based on a mimetic immunoassay for potential accurate diabetic nephropathy diagnosis
Authors: Wang Yiting , Hu Yang , Wang Ru , Zhang Wei , Mao Huiting , Yuan Chuanjun , Hua Ruinian
Published: September 2023

An ultrasensitive non-proteinuria assay platform to accurately diagnose DN within 20 min based on the mimetic immunoassay.
High-throughput screening and quantification of pesticides in Lilii Bulbus using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry
Authors: Chen Ting , Zhu Renyuan , Zhang Wen , Li Jian , Qiu Guoyu , Wu Fuxiang , Xu Yanli , Chen Min , Qi Pengfei
Published: September 2023

This work presents an analytical method for rapidly screening multiple pesticide residues using QuEChERS combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
Ag(i)-catalyzed dearomatizing spirocyclization/nucleophile addition cascade reactions of indole-tethered ynones
Authors: Bag Debojyoti , Sawant Sanghapal D.
Published: September 2023

Ag(i)-catalyzed highly diastereoselective construction of divergent spiroindolines via dearomatizing indole-ynone spirocyclization/nucleophile addition cascade reaction is disclosed herein.
Constructing a pyrene-based dimer in a crystal by adjusting the steric hindrance over the pyrene plane
Authors: Xia Zhou-An , Zhang Xiangyu , Xi Chang , Bai Qing , Liu Haichao , Zhang Shi-Tong , Yang Bing
Published: September 2023

The presence of an ortho-linked substituent in pyrene can lead to steric hindrance on one side of the pyrene plane, which prevents the formation of undesired interactions and promotes the selective formation of dimers in a desired orientation.
Nanostructuring and stabilization of metastable rock-salt ZnO: impact of high-pressure media and compression geometry
Authors: Sokolov Petr S. , Courac Alexandre , Solozhenko Vladimir L.
Published: September 2023

Record thermal stability (800 K) and Vickers hardness (7 GPa) of the rock-salt high-pressure phase of ZnO have been achieved for single-phase nanostructured bulk by using the combination of appropriate compression conditions and pressure medium.
Composition and structural characteristics of compressed alkaline earth metal hydrides
Authors: Tao Ya-Le , Zeng Wei , Gao Juan , Liu Zheng-Tang , Jiao Zhen , Liu Qi-Jun
Published: September 2023

The metallization of alkaline earth metal hydrides offers a way to achieve near-room temperature superconductivity.
Integrating autonomy into automated research platforms
Authors: Canty Richard B. , Koscher Brent A. , McDonald Matthew A. , Jensen Klavs F.
Published: September 2023

The strict specification required for automatization to efficiently and reproducibly act in familiar domains restricts the flexibility needed for autonomy when exploring new domains, requiring self-driving labs to balance autonomy and automation.
Ce-doped indium oxide nanozymes with peroxidase-like activity induced by cerium–indium synergy for colourimetric detection of H2O2
Authors: Liu Bin , Ruan Haoliang , Li Chengyi , Yao Jie , Wei Bei , Wang Lei , Ban Shurong , Xie Jun
Published: September 2023

InCex has a higher catalytic efficiency due to the presence of more oxygen vacancies and higher Ce3+ content, which can provide a wide range of binding sites for TMB, and also can accelerate the electron transfer rate.
Unusual tellurium(iv) mediated cyclisation diols into dihydroxazoles with potential anticancer activity
Authors: D’Arcy Kenneth , Schäfer Tim , De Franco Michele , Ricco Raffaele , Gandin Valentina , Sanz Miguel Pablo J. , Montagner Diego
Published: September 2023

Unusual tellurium(iv) mediated cyclisation of diols into dihydroxazoles with potential anticancer activity.
Heterometallic Ru–Ir carbonyl clusters as catalyst precursors for hydrogenation and hydrogen transfer reactions
Authors: Forti Francesca , Cesari Cristiana , Bortoluzzi Marco , Femoni Cristina , Iapalucci Maria Carmela , Zacchini Stefano
Published: September 2023

Heterometallic Ru–Ir hydride carbonyl clusters were synthesized and tested as catalyst precursors for hydrogenation of 4-fluoroacetophenone and trans-cinnamaldehyde.
TMDC ternary alloy–based triboelectric nanogenerators with giant photo-induced enhancement
Authors: Bhattacharya Didhiti , Mukherjee Shubhrasish , Mitra Rajib Kumar , Ray Samit Kumar
Published: September 2023

The photosensitive triboelectric nanogenerator exhibits an outstanding photoresponsivity (45.5 V mW−1) and enhanced energy harvesting ability under visible light illumination, and this wearable TENG is promising for smart device technology.
Highly electron-deficient ultrathin Co nanosheets supported on mesoporous Cr2O3 for catalytic hydrogen evolution from ammonia borane
Authors: Song Jin , Wu Fenglong
Published: September 2023

Highly electron-deficient ultrathin Co nanosheets supported on mesoporous Cr2O3 for catalytic hydrogen evolution from ammonia borane under visible irradiation.
Quantum anomalous valley Hall effect in ferromagnetic MXenes with asymmetric functionalization
Authors: Li Shuo , Frauenheim Thomas , He Junjie
Published: September 2023

The Janus Cr2COF MXene becomes an intrinsic Chern insulator with large spin–valley polarization and belongs to the family of quantum anomalous valley Hall effect materials.
Sintering resistance of Pd single atoms on steam-modified ceria: deciphering the role of hydroxyl groups
Authors: An Yuanyuan , Chen Sheng-Yu , Zhou Li , Wang Beibei , Hao Guoxiu , Chen Junchen , Wang Yanli , Zhang Hui , Peng Zheng , Yang Tsung-Cheng , Yang Chia-Min , Chen Jeng-Lung , Tsung Chia-Kuang , Liu Zhi , Chou Lien-Yang
Published: September 2023

OH-modified CeO2 not only anchors the loading sites of Pd, forming a stable OH-assisted doping structure to enhance sintering resistance, but also increases the active sites of Pd, enabling sustainable activity for low-temperature CO oxidation.
Gate-tunable rectification and photoresponse in a MoTe2/SnS2 van der Waals heterostructure based P–N diode
Authors: Elahi Ehsan , Khan Muhammad Asghar , Jeon Jaeho , Jerng Sahng-Kyoon , Al-Kahtani Abdullah A. , Noh Hwayong
Published: September 2023

The p–n junction, one of the prominent electrical components capable of being utilized in electronics and optoelectronics, has attracted renewed interest due to recent research in two-dimensional (2D) materials.
A morphological study of random nanostructured external light extraction layers for enhancing optical characteristics of OLEDs
Authors: Choi Geun Su , Kang Shin Woo , Bae Eun Jeong , Ju Byeong-Kwon , Park Young Wook
Published: September 2023

This study presents an in-depth investigation of nano-pillar-based external light extraction techniques, focusing on the analysis of light extraction characteristics based on the pillar and plane structures.
Phenylene-bridged cyclic multi-resonance TADF emitters for high-efficiency and high-color-purity sky-blue OLEDs with EQE of 30%
Authors: Kumada Kengo , Sasabe Hisahiro , Matsuya Misaki , Yoshida Naoto , Hoshi Keigo , Nakamura Takeru , Nemma Haruki , Kido Junji
Published: September 2023

Three phenylene-bridged MR-TADF emitters with different numbers of carbazole units are developed. These emitters exhibit sky-blue emission around 480 nm with a small FWHM of ∼31 nm, near-unity PLQY, and an EQE of nearly 30%.
A discounted‐UCB1‐tuned plus Q‐learning based anti‐jamming routing algorithm for wireless mesh networks
Authors: Ding Huihui , Zhou Quan , Niu Yingtao , Xiang Peng , Zhou Zhanyang
Published: September 2023

To achieve autonomous anti‐jamming routing for wireless mesh networks (WMNs) under the threat of unknown removable jammers, a Q‐learning anti‐jamming routing algorithm using the improved upper‐confidence‐bound (UCB) algorithm is proposed in this paper. Specifically, the WMNs anti‐jamming routing path finding problem is first modelled as a Markov decision process. Then, to address the slow‐convergence anti‐jamming strategy induced by the drawback that the preset parameters uniquely determine the length of the traditional Q‐learning exploration process, a discounted‐UCB‐tuned algorithm (Dis‐UCB1‐tuned) is adopted as the decision algorithm to replace the ε‐greedy or softmax algorithm in traditional Q‐learning. Finally, the simulation results demonstrate the superiority of the proposed anti‐jamming scheme over the UCB‐based Q learning(UCBQ) algorithm, Dyna‐Q algorithm, and the traditional Q‐learning algorithm. To elaborate, the proposed scheme can fast converge to a superior anti‐jamming routing without any prior knowledge of jamming environment, and its performance is also independent with the preset parameter.
Ag‐doped Ti3C2Tx sensor: A promising candidate for low‐concentration H2S gas sensing
Authors: Zeng Fuping , Feng Xiaoxuan , Chen Xiaoyue , Qiu Hao , Yan Yiming , Yao Qiang , Tang Ju
Published: September 2023

Trace hydrogen sulphide (H2S) could reflect the severity of insulation faults in gas‐insulated switchgear (GIS), therefore, accurate and fast detection of low‐concentration H2S is important for on‐line monitoring, fault diagnosis, and state evaluation in GIS. Ag‐Ti3C2Tx chemiresistive‐type sensors were fabricated via drop‐coating with self‐reduction synthesised Ag‐doped Ti3C2Tx. The as‐prepared sensors exhibited an excellent sensitivity and selectivity to H2S with an extremely low detection of limit of 18.57 parts per billion (ppb) at 25°C (room temperature). The response of Ag‐Ti3C2Tx sensor to 10 parts per million (ppm) H2S was enhanced ∼12 times than that of the pristine Ti3C2Tx sensor. The compositing of Ti3C2Tx with Ag nanoparticles (NPs) enabled the fast response/recovery time for H2S detection. Further analysis found that the enhanced H2S sensing performances could be attributed to chemical sensitisation, adsorbed oxygen species regulation and high Brunauer–Emmett–Teller (BET) surface area. This study paves the way for Ag‐Ti3C2Tx as room‐temperature sensing materials to detect low‐concentration H2S in GIS.
A heliospheric density and magnetic field model
Authors: Mann G. , Warmuth A. , Vocks C. , Rouillard A. P.
Published: September 2023

Context. The radial evolution of the density of the plasma and the magnetic field in the heliosphere, especially in the region between the solar corona and the Earth’s orbit, has been a topic of active research for several decades. Both remote-sensing observations and in situ measurements by spacecraft such as HELIOS, Ulysses, and WIND have provided critical data on this subject. The NASA space mission Parker Solar Probe (PSP), which will approach the Sun down to a distance of 9.9 solar radii on December 24, 2024, gives new insights into the structure of the plasma density and magnetic field in the heliosphere, especially in the near-Sun interplanetary space. This region is of particular interest because the launch and evolution of coronal mass ejections (CMEs), which can influence the environment of our Earth (usually called space weather), takes place there.

Aims. Because of the new data from PSP, it is time to revisit the subject of the radial evolution of the plasma density and magnetic field in the heliosphere. To do this, we derive a radial heliospheric density and magnetic field model in the vicinity of the ecliptic plane above quiet equatorial regions. The model agrees well with the measurements in the sense of a global long-term average.

Methods. The radial evolution of the density and solar wind velocity is described in terms of Parker’s wind equation. A special solution of this equation includes two integration constants that are fitted by the measurements. For the magnetic field, we employed a previous model in which the magnetic field is describe by a superposition of the magnetic fields of a dipole and a quadrupole of the quiet Sun and a current sheet in the heliosphere.

Results. We find the radial evolution of the electron and proton number density as well as the radial component of the magnetic field and the total field strength in the heliosphere from the bottom of the corona up to a heliocentric distance of 250 solar radii. The modelled values are consistent with coronal observations, measurements at 1 AU, and with the recent data from the inner heliosphere provided by PSP.

Conclusions. With the knowledge of the radial evolution of the plasma density and the magnetic field in the heliosphere the radial behaviour of the local Alfvén speed can be calculated. It can can reach a local maximum of 392 km s−1 at a distance of approximately 4 solar radii, and it exceeds the local solar wind speed at distances in the range of 3.6−13.7 solar radii from the centre of the Sun.
TRAVELING WAVES IN HEMODYNAMIC EQUATIONS WITH THE KOITER SHELL
Authors: Vasyutkin Sergey , Chupakhin Alexander
Published: September 2023

We consider a one-dimensional model of hemodynamics for a tube defined by a Koiter shell, and investigate traveling wave solutions. The system of partial differential equations is reduced to a fourth-order ordinary differential equation for such solutions. We find a single equilibrium point and determine the condition for the changing type of the equilibria for the corresponding system of first-order differential equations. The conditions for changing the type of the equilibrium point are formulated. Then we introduce the classification of blood flow regimes relative to the type of the equilibrium point. Numerical experiments are carried out to confirm and analyze the obtained results, various regimes of blood flow are considered.