bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reg3γ: current understanding and future therapeutic opportunities in metabolic disease
Authors: Shin Jae Hoon , Bozadjieva-Kramer Nadejda , Seeley Randy J. 
Published: August 2023

AbstractRegenerating family member gamma, Reg3γ (the mouse homolog of human REG3A), belonging to the antimicrobial peptides (AMPs), functions as a part of the host immune system to maintain spatial segregation between the gut bacteria and the host in the intestine via bactericidal activity. There is emerging evidence that gut manipulations such as bariatric surgery, dietary supplementation or drug treatment to produce metabolic benefits alter the gut microbiome. In addition to changes in a wide range of gut hormones, these gut manipulations also induce the expression of Reg3γ in the intestine. Studies over the past decades have revealed that Reg3γ not only plays a role in the gut lumen but can also contribute to host physiology through interaction with the gut microbiota. Herein, we discuss the current knowledge regarding the biology of Reg3γ, its role in various metabolic functions, and new opportunities for therapeutic strategies to treat metabolic disorders.
Genome editing in the treatment of ocular diseases
Authors: Choi Elliot H. , Suh Susie , Sears Avery E. , Hołubowicz Rafał , Kedhar Sanjay R. , Browne Andrew W. , Palczewski Krzysztof 
Published: August 2023

AbstractGenome-editing technologies have ushered in a new era in gene therapy, providing novel therapeutic strategies for a wide range of diseases, including both genetic and nongenetic ocular diseases. These technologies offer new hope for patients suffering from previously untreatable conditions. The unique anatomical and physiological features of the eye, including its immune-privileged status, size, and compartmentalized structure, provide an optimal environment for the application of these cutting-edge technologies. Moreover, the development of various delivery methods has facilitated the efficient and targeted administration of genome engineering tools designed to correct specific ocular tissues. Additionally, advancements in noninvasive ocular imaging techniques and electroretinography have enabled real-time monitoring of therapeutic efficacy and safety. Herein, we discuss the discovery and development of genome-editing technologies, their application to ocular diseases from the anterior segment to the posterior segment, current limitations encountered in translating these technologies into clinical practice, and ongoing research endeavors aimed at overcoming these challenges.
ALKBH5 facilitates CYP1B1 mRNA degradation via m6A demethylation to alleviate MSC senescence and osteoarthritis progression
Authors: Ye Guiwen , Li Jinteng , Yu Wenhui , Xie Zhongyu , Zheng Guan , Liu Wenjie , Wang Shan , Cao Qian , Lin Jiajie , Su Zepeng , Li Dateng , Che Yunshu , Fan Shuai , Wang Peng , Wu Yanfeng , Shen Huiyong 
Published: August 2023

AbstractImproving health and delaying aging is the focus of medical research. Previous studies have shown that mesenchymal stem cell (MSC) senescence is closely related to organic aging and the development of aging-related diseases such as osteoarthritis (OA). m6A is a common RNA modification that plays an important role in regulating cell biological functions, and ALKBH5 is one of the key m6A demethylases. However, the role of m6A and ALKBH5 in MSC senescence is still unclear. Here, we found that the m6A level was enhanced and ALKBH5 expression was decreased in aging MSCs induced by multiple replications, H2O2 stimulation or UV irradiation. Downregulation of ALKBH5 expression facilitated MSC senescence by enhancing the stability of CYP1B1 mRNA and inducing mitochondrial dysfunction. In addition, IGF2BP1 was identified as the m6A reader restraining the degradation of m6A-modified CYP1B1 mRNA. Furthermore, Alkbh5 knockout in MSCs aggravated spontaneous OA in mice, and overexpression of Alkbh5 improved the efficacy of MSCs in OA. Overall, this study revealed a novel mechanism of m6A in MSC senescence and identified promising targets to protect against aging and OA.
SLC39A10 promotes malignant phenotypes of gastric cancer cells by activating the CK2-mediated MAPK/ERK and PI3K/AKT pathways
Authors: Ren Xiaojuan , Feng Chao , Wang Yubo , Chen Pu , Wang Simeng , Wang Jianling , Cao Hongxin , Li Yujun , Ji Meiju , Hou Peng 
Published: August 2023

AbstractSolute carrier family 39 member 10 (SLC39A10) belongs to a subfamily of zinc transporters and plays a key role in B-cell development. Previous studies have reported that its upregulation promotes breast cancer metastasis by enhancing the influx of zinc ions (Zn2+); however, its role in gastric cancer remains totally unclear. Here, we found that SLC39A10 expression was frequently increased in gastric adenocarcinomas and that SLC39A10 upregulation was strongly associated with poor patient outcomes; in addition, we identified SLC39A10 as a direct target of c-Myc. Functional studies showed that ectopic expression of SLC39A10 in gastric cancer cells dramatically enhanced the proliferation, colony formation, invasiveness abilities of these gastric cancer cells and tumorigenic potential in nude mice. Conversely, SLC39A10 knockdown inhibited gastric cancer cell proliferation and colony formation. Mechanistically, SLC39A10 exerted its carcinogenic effects by increasing Zn2+ availability and subsequently enhancing the enzyme activity of CK2 (casein kinase 2). As a result, the MAPK/ERK and PI3K/AKT pathways, two major downstream effectors of CK2, were activated, while c-Myc, a downstream target of these two pathways, formed a vicious feedback loop with SLC39A10 to drive the malignant progression of gastric cancer. Taken together, our data demonstrate that SLC39A10 is a functional oncogene in gastric cancer and suggest that targeting CK2 is an alternative therapeutic strategy for gastric cancer patients with high SLC39A10 expression.
Dysregulation of the Wnt/β-catenin signaling pathway via Rnf146 upregulation in a VPA-induced mouse model of autism spectrum disorder
Authors: Park Gaeun , Jang Wooyoung Eric , Kim Seoyeon , Gonzales Edson Luck , Ji Jungeun , Choi Seunghwan , Kim Yujin , Park Ji Hwan , Mohammad Hazara Begum , Bang Geul , Kang Minkyung , Kim Soobin , Jeon Se Jin , Kim Jin Young , Kim Kwang Pyo , Shin Chan Young , An Joon-Yong , Kim Min-Sik , Lee Yong-Seok 
Published: August 2023

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.
Bellidifolin ameliorates isoprenaline-induced cardiac hypertrophy by the Nox4/ROS signalling pathway through inhibiting BRD4
Authors: Zhou Dingyan , Liu Weizhe , Zhang Juanjuan , Dong Yucui , Wu Jiangli , Zhang Yu , Dai Cheng , Zhang Tingting , Yang Gaoshan , Zhang Yue , Li Aiying 
Published: August 2023

AbstractTo date, there is no effective therapy for pathological cardiac hypertrophy, which can ultimately lead to heart failure. Bellidifolin (BEL) is an active xanthone component of Gentianella acuta (G. acuta) with a protective function for the heart. However, the role and mechanism of BEL action in cardiac hypertrophy remain unknown. In this study, the mouse model of cardiac hypertrophy was established by isoprenaline (ISO) induction with or without BEL treatment. The results showed that BEL alleviated cardiac dysfunction and pathological changes induced by ISO in the mice. The expression of cardiac hypertrophy marker genes, including ANP, BNP, and β-MHC, were inhibited by BEL both in mice and in H9C2 cells. Furthermore, BEL repressed the epigenetic regulator bromodomain-containing protein 4 (BRD4) to reduce the ISO-induced acetylation of H3K122 and phosphorylation of RNA Pol II. The Nox4/ROS/ADAM17 signalling pathway was also inhibited by BEL in a BRD4 dependent manner. Thus, BEL alleviated cardiac hypertrophy and cardiac dysfunction via the BRD4/Nox4/ROS axes during ISO-induced cardiac hypertrophy. These findings clarify the function and molecular mechanism of BEL action in the therapeutic intervention of cardiac hypertrophy.
Consanguinity and willingness to perform premarital genetic screening in Sudan
Authors: Elhadi Yasir Ahmed Mohammed , Alrawa Salma S. , Alfadul Esraa S. A. , Mahgoub Esra Abdallah Abdalwahed , El-Osta Austen , Belal Safaa Abdalazeem , Lucero-Prisno Don Eliseo , El Dabbah Noha Ahmed , Yahia Ashraf 
Published: August 2023

AbstractConsanguineous marriage is prevalent in certain world regions due to cultural, economic, and social reasons. However, it can lead to negative consequences including an increased risk of genetic disorders in offspring. Premarital genetic screening (PMGS) is an important tool to identify and manage these risks before marriage. This study aimed to assess the magnitude of consanguineous marriage, knowledge of genetic diseases and PMGS, and attitudes and willingness to perform PMGS in Sudan. A national household survey was conducted using a multistage sampling technique, with a sample size of 2272 participants. Data were collected from December 2022 to March 2023 using an interviewer-administered questionnaire. A significant proportion of respondents (364/850, 42.8%) were married to consanguineal partners, with various types of relatedness. Moreover, 32.1% (242/755) of single respondents were planning to marry a close relative, signifying the likely persistence of consanguineous marriages in Sudan. The level of knowledge regarding genetic diseases and PMGS was relatively low in many states of Sudan, indicating the need for increased awareness interventions. A significant number of participants (85.2%) agreed that premarital screening is effective in reducing genetic diseases, whereas 71.2% supported the introduction of a mandatory PMGS program. Excluding married participants, 82.3% (1265/1537) of respondents were willing to perform PMGS, if implemented. These findings reflect the public positive attitude towards introducing the PMGS program and policies in Sudan and underscore the importance of addressing the knowledge gap of PMGS before such a potential implementation.
Dressed-state control of effective dipolar interaction between strongly-coupled solid-state spins
Authors: Lee Junghyun , Tatsuta Mamiko , Xu Andrew , Bauch Erik , Ku Mark J. H. , Walsworth Ronald L. 
Published: August 2023

AbstractStrong interactions between defect spins in many-body solid-state quantum systems are a crucial resource for exploring non-classical states. However, they face the key challenge of controlling interactions between the defect spins, since they are spatially fixed inside the host lattice. In this work, we present a dressed state approach to control the effective dipolar coupling between solid-state spins and demonstrate this scheme experimentally using two strongly-coupled nitrogen vacancy (NV) centers in diamond. Through Ramsey spectroscopy on the sensor spin, we detect the change of the effective dipolar field generated by the control spin prepared in different dressed states. To observe the change of interaction dynamics, we deploy spin-lock-based polarization transfer measurements between the two NV spins in different dressed states. This scheme allows us to control the distribution of interaction strengths in strongly interacting spin systems, which can be a valuable tool for generating multi-spin correlated states for quantum-enhanced sensing.
A chromosome-level genome assembly of a deep-sea starfish (Zoroaster cf. ophiactis)
Authors: Liu Jun , Zhou Yang , Pu Yujin , Zhang Haibin 
Published: August 2023

AbstractUnderstanding of adaptation and evolution of organisms in the deep sea requires more genomic resources. Zoroaster cf. ophiactis is a sea star in the family Zoroasteridae occurring exclusively in the deep sea. In this study, a chromosome-level genome assembly for Z. cf. ophiactis was generated by combining Nanopore long-read, Illumina short-read, and Hi-C sequencing data. The final assembly was 1,002.0 Mb in length, with a contig N50 of 376 Kb and a scaffold N50 of 40.4 Mb, and included 22 pseudo-chromosomes, covering 92.3% of the assembly. Completeness analysis evaluated with BUSCO revealed that 95.91% of the metazoan conserved genes were complete. Additionally, 39,426 protein-coding genes were annotated for this assembly. This chromosome-level genome assembly represents the first high-quality genome for the deep-sea Asteroidea, and will provide a valuable resource for future studies on evolution and adaptation of deep-sea echinoderms.
Effects of neutron radiation generated in deep space-like environments on food resources
Authors: Hatsuda Machiko , Kawasaki Hiroaki , Shigenaga Ayako , Taketani Atsushi , Takanashi Takaoki , Wakabayashi Yasuo , Otake Yoshie , Kamata Yayoi , Ichinose Akari , Nishioka Honoka , Kimura Hayato , Koganei Yumi , Komoriya Shiomi , Sakai Miyu , Hamano Yui , Yoshida Maria , Yamakura Fumiyuki 
Published: August 2023

AbstractThe impact of deep space cosmic rays on food resources is as important as the risks of cosmic rays to the human body. This study demonstrates the potential for neutrons as secondary radiation in deep space spacecraft to cause meat activation and oxidative modification of proteins and lipids. We conducted a series of experiments such as the neutron irradiation experiment, the radioactivation analysis and the biochemical analysis. Neutrons with energies from 1 to 5 MeV with doses from 0.01 Gy to 4 Gy were irradiated by the RIKEN accelerated-driven neutron source (RANS). Radioactive nuclei, 24Na, 42K, and 38Cl, were detected in the neutron-irradiated meat. The modification products of the proteins by oxidative nitration, 6-nitrotryptophan (6NO2Trp), and by a lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE), were detected in several proteins with neutron dose dependent. The proteome analysis showed that many oxidative modifications were detected in actin and myosin which are major proteins of myofibrils. This study is of crucial importance not only as risk factors for human space exploration, but also as fundamental effects of radiation on the components of the human body.
Identification of RNF150 as the hub gene associated with microsatellite instability in gastric cancer
Authors: Pan Jun , Lan Qingzhi , Li Shengbao 
Published: August 2023

AbstractGastric cancer (GC) is a common digestive tract malignancy with the sixth global incidence and third cancer-related deaths, respectively. Microsatellite instability (MSI), accounting for one of the molecular subtypes of GC, plays an important role in GC and is affected by a sophisticated network of gene interactions. In this study, we aimed to explore the expression pattern and clinical performance of MSI related gene in GC patients. Weighted gene co-expression network analysis (WGCNA) was exploited to single out the vital module and core genes in TCGA database. We applied the protein–protein interaction (PPI) and survival analysis to propose and confirm RNF150 as the hub gene in GC. Finally, we utilized immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) to explore the expression pattern of RNF150 in GC patients. With the highest weight correlation and standard correlation, RNF150 was selected as the hub gene for following validation. In validation, data obtained from the test sets showed a lower expression of RNF150 in MSI GC compared to microsatellite stability (MSS) GC. Moreover, survival analysis shows that MSI GC patients with a lower RNF150 expression level displayed the longer OS time. Compared to the expression in normal gastric tissues, the protein level of RNF150 was virtually up-regulated in ten cases of GC tissues. Furthermore, RNF150 protein level was decreased in MSI GC samples compared to MSS GC samples. When validated the mRNA expression with RT-PCR in fresh GC tissues, we also found the similar trend. RNF150 was identified as a novel MSI-related gene in GC. It is expected to be an auspicious prognostic biomarker for GC patients.
Bose glass and Fermi glass
Authors: Takahashi Korekiyo , Nakatsugawa Keiji , Sakoda Masahito , Nanao Yoshiko , Nobukane Hiroyoshi , Obuse Hideaki , Tanda Satoshi 
Published: August 2023

AbstractIt is known that two-dimensional superconducting materials undergo a quantum phase transition from a localized state to superconductivity. When the disordered samples are cooled, bosons (Cooper pairs) are generated from Fermi glass and reach superconductivity through Bose glass. However, there has been no universal expression representing the transition from Fermi glass to Bose glass. Here, we discovered an experimental renormalization group flow from Fermi glass to Bose glass in terms of simple $$\beta$$
β
-function analysis. To discuss the universality of this flow, we analyzed manifestly different systems, namely a Nd-based two-dimensional layered perovskite and an ultrathin Pb film. We find that all our experimental data for Fermi glass fall beautifully into the conventional self-consistent $$\beta$$
β
-function. Surprisingly, however, flows perpendicular to the conventional $$\beta$$
β
-function are observed in the weakly localized regime of both systems, where localization becomes even weaker. Consequently, we propose a universal transition from Bose glass to Fermi glass with the new two-dimensional critical sheet resistance close to $$R_\Box = h/e^{2}$$

R
□

=
h
/

e
2

.
The prevalence of chronic and episodic loneliness and social isolation from a longitudinal survey
Authors: Lim Michelle H. , Manera Karine E. , Owen Katherine B. , Phongsavan Philayrath , Smith Ben J. 
Published: August 2023

AbstractLoneliness and social isolation, experienced more long-term, has been shown to increase mortality and lead to poorer health outcomes in specific cohorts. However, it is unclear what the prevalence of chronic loneliness and social isolation is, and which demographic groups are most at risk of reporting more chronic forms. A psychometrically validated classification system was used to identify people who met criteria for episodic and chronic loneliness and social isolation using the Household Income and Labour Dynamics in Australia (HILDA) survey waves 14–18. The prevalence of loneliness (overall 34%; 21% episodic, 13% chronic) far exceeded that of social isolation (overall 17%; 13% episodic, 4% chronic). There was consistency in the demographic characteristics (from age, sex, household type, income) of those who experienced loneliness and social isolation. However, people with a long-term health condition had an elevated risk of episodic loneliness (AOR 1.24, 95% CI 1.11–1.39) and a markedly higher risk of chronic loneliness (AOR 2.01, 95% CI 1.76–2.29), compared with those without a long-term health condition. Loneliness, both episodic and chronic subtypes, is more prevalent than social isolation. However, both chronic loneliness and social isolation remains neglected and poorly targeted within current practice and policy.
Comparison of infection and human immune responses of two SARS-CoV-2 strains in a humanized hACE2 NIKO mouse model
Authors: Yong Kylie Su Mei , Anderson Danielle E. , Zheng Adrian Kang Eng , Liu Min , Tan Sue Yee , Tan Wilson Wei Sheng , Chen Qingfeng , Wang Lin-Fa 
Published: August 2023

AbstractThe COVID-19 pandemic has sickened millions, cost lives and has devastated the global economy. Various animal models for experimental infection with SARS-CoV-2 have played a key role in many aspects of COVID-19 research. Here, we describe a humanized hACE2 (adenovirus expressing hACE2) NOD-SCID IL2Rγ−/− (NIKO) mouse model and compare infection with ancestral and mutant (SARS-CoV-2-∆382) strains of SARS-CoV-2. Immune cell infiltration, inflammation, lung damage and pro-inflammatory cytokines and chemokines was observed in humanized hACE2 NIKO mice. Humanized hACE2 NIKO mice infected with the ancestral and mutant SARS-CoV-2 strain had lung inflammation and production of pro-inflammatory cytokines and chemokines. This model can aid in examining the pathological basis of SARS-CoV-2 infection in a human immune environment and evaluation of therapeutic interventions.
DNA-PK inhibition extends the therapeutic effects of Top2 poisoning to non-proliferating cells, increasing activity at a cost
Authors: Wang Taixiang , Kyle Alastair H. , Baker Jennifer H. E. , Liu Nannan A. , Banáth Judit P. , Minchinton Andrew I. 
Published: August 2023

AbstractType II topoisomerase (Top2) poisoning therapy is used to treat a broad range of cancers via induction of double strand breaks (DSBs) in cells undergoing replication and transcription. Preventing the repair of DSBs via inhibition of DNA-PK, an inhibitor of non-homologous end-joining (NHEJ), increases cell kill with Top2 poisons and has led to the initiation of several clinical trials. To elucidate the cellular mechanisms leading to synergistic activity of dual DNA-PK/Top2 inhibition we looked at their effects in cycling versus non-cycling cells, in 3D spheroids and in xenograft models. Combined DNA-PK/Top2 inhibition was found to not only increase the cell kill in proliferating cells, the cell population that is typically most vulnerable to Top2 poisoning, but also in non-proliferative but transcriptionally active cells. This effect was observed in both cancer and normal tissue models, killing more cells than high concentrations of etoposide alone. The combination treatment delayed tumor growth in mice compared to Top2 poisoning alone, but also led to increased toxicity. These findings demonstrate sensitization of Top2β-expressing, non-cycling cells to Top2 poisoning by DNA-PK inhibition. Expansion of the target cell population of Top2 poison treatment to include non-proliferating cells via combination with DNA damage repair inhibitors has implications for efficacy and toxicity of these combinations, including for inhibitors of DNA-PK currently in clinical trial.