bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of an automated robotic microinjection system for batch injection of zebrafish embryos and larvae
Authors: Guo Zhongyi , Ai Nana , Ge Wei , Xu Qingsong 
Published: January 2024

AbstractThis paper presents the design of a vision-based automated robotic microinjection system for batch injection of both zebrafish embryos and larvae. A novel visual recognition algorithm based on an automatic threshold and excessive dilatation is introduced to accurately identify the center of zebrafish embryos and larval yolks. A corresponding software system is developed using the producer-consumer model as the framework structure, and a friendly user interface is designed to allow operators to choose from a range of desired functions according to their different needs. In addition, a novel microstructural agarose device is designed and fabricated to simultaneously immobilize mixed batches of embryos and larvae. Moreover, a prototype microinjection system is fabricated by integrating hardware devices with visual algorithms. An experimental study is conducted to verify the performance of the robotic microinjection system. The results show that the reported system can accurately identify zebrafish embryos and larvae and efficiently complete batch microinjection tasks of the mixtures with an injection success rate of 92.05% in 13.88 s per sample. Compared with manual and existing microinjection systems, the proposed system demonstrates the merits of versatility, excellent efficiency, high success rate, high survival rate, and sufficient stability.
RNA processing mechanisms contribute to genome organization and stability in B cells
Authors: Miglierina Emma , Ordanoska Delfina , Le Noir Sandrine , Laffleur Brice 
Published: January 2024

AbstractRNA processing includes post-transcriptional mechanisms controlling RNA quality and quantity to ensure cellular homeostasis. Noncoding (nc) RNAs that are regulated by these dynamic processes may themselves fulfill effector and/or regulatory functions, and recent studies demonstrated the critical role of RNAs in organizing both chromatin and genome architectures. Furthermore, RNAs can threaten genome integrity when accumulating as DNA:RNA hybrids, but could also facilitate DNA repair depending on the molecular context. Therefore, by qualitatively and quantitatively fine-tuning RNAs, RNA processing contributes directly or indirectly to chromatin states, genome organization, and genome stability. B lymphocytes represent a unique model to study these interconnected mechanisms as they express ncRNAs transcribed from key specific sequences before undergoing physiological genetic remodeling processes, including V(D)J recombination, somatic hypermutation, and class switch recombination. RNA processing actors ensure the regulation and degradation of these ncRNAs for efficient DNA repair and immunoglobulin gene remodeling while failure leads to B cell development alterations, aberrant DNA repair, and pathological translocations. This review highlights how RNA processing mechanisms contribute to genome architecture and stability, with emphasis on their critical roles during B cell development, enabling physiological DNA remodeling while preventing lymphomagenesis.
QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study
Authors: Huang Yan , Yang Yunpeng , Zhao Yuanyuan , Zhao Hongyun , Zhou Ningning , Zhang Yaxiong , Chen Likun , Zhou Ting , Chen Gang , Wu Ting , Lu Lu , Xue Shilin , Kang Xiaoyan , Zhang Li , Fang Wenfeng 
Published: January 2024

AbstractFirst-line chemoimmunotherapy (with or without bevacizumab) has improved outcomes in advanced non-small cell lung cancer (NSCLC). Here, this open-label, multi-cohort phase II study (NCT05329025) was done to investigate the safety and efficacy of QL1706 (a single bifunctional MabPair product against PD-1 and CTLA-4) and chemotherapy with or without bevacizumab in this population. Patients were enrolled into five different cohorts based on genotype (cohorts 1-4, epidermal growth factor receptor [EGFR] wild-type; cohort 5, EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors [TKIs]). Between June 11, 2021 and December 29, 2021, 91 patients were enrolled. Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia (60 [65.9%]), infusion-related reactions (48 [52.7%]), and pruritus (44 [48.4%]). Grade ≥ 3 TRAEs occurred in 30 (33.0%) patients. Twenty-seven (45%) patients with wild-type EGFR achieved partial response (PR) (objective response rate [ORR] = 45%) and had a median progression-free survival (mPFS) of 6.8 months (95% CI: 5.2-9.7). For 31 patients harboring mutated EGFR, 17 (54.8%) achieved PR (ORR = 54.8%), with an mPFS of 8.5 months (95% CI: 5.72-not evaluable). Overall, QL1706 plus chemotherapy, regardless of having bevacizumab, was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting. Moreover, QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy, demonstrating a potential for treating this population.
A phase I study of ATR inhibitor gartisertib (M4344) as a single agent and in combination with carboplatin in patients with advanced solid tumours
Authors: Burris Howard A. , Berlin Jordan , Arkenau Tobias , Cote Gregory M. , Lolkema Martijn P. , Ferrer-Playan Jordi , Kalapur Anup , Bolleddula Jayaprakasam , Locatelli Giuseppe , Goddemeier Thomas , Gounaris Ioannis , de Bono Johann 
Published: January 2024

Abstract
Background
Gartisertib is an oral inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), a key kinase of the DNA damage response. We aimed to determine the safety and tolerability of gartisertib ± carboplatin in patients with advanced solid tumours.

Methods
This phase I open-label, multicenter, first-in-human study comprised four gartisertib cohorts: A (dose escalation [DE]; Q2W); A2 (DE; QD/BID); B1 (DE+carboplatin); and C (biomarker-selected patients).

Results
Overall, 97 patients were enroled into cohorts A (n = 42), A2 (n = 26), B1 (n = 16) and C (n = 13). The maximum tolerated dose and recommended phase II dose (RP2D) were not declared for cohorts A or B1. In cohort A2, the RP2D for gartisertib was determined as 250 mg QD. Gartisertib was generally well-tolerated; however, unexpected increased blood bilirubin in all study cohorts precluded further DE. Investigations showed that gartisertib and its metabolite M26 inhibit UGT1A1-mediated bilirubin glucuronidation in human but not dog or rat liver microsomes. Prolonged partial response (n = 1 [cohort B1]) and stable disease >6 months (n = 3) did not appear to be associated with biomarker status. Exposure generally increased dose-dependently without accumulation.

Conclusion
Gartisertib was generally well-tolerated at lower doses; however, unexpected liver toxicity prevented further DE, potentially limiting antitumour activity. Gartisertib development was subsequently discontinued.

ClinicalTrials.gov
NCT02278250.
CYLD induces high oxidative stress and DNA damage through class I HDACs to promote radiosensitivity in nasopharyngeal carcinoma
Authors: Li Yueshuo , Yang Chenxing , Xie Longlong , Shi Feng , Tang Min , Luo Xiangjian , Liu Na , Hu Xudong , Zhu Yongwei , Bode Ann M. , Gao Qiang , Zhou Jian , Fan Jia , Li Xuejun , Cao Ya 
Published: January 2024

AbstractAbnormal expression of Cylindromatosis (CYLD), a tumor suppressor molecule, plays an important role in tumor development and treatment. In this work, we found that CYLD binds to class I histone deacetylases (HDAC1 and HDAC2) through its N-terminal domain and inhibits HDAC1 activity. RNA sequencing showed that CYLD-HDAC axis regulates cellular antioxidant response via Nrf2 and its target genes. Then we revealed a mechanism that class I HDACs mediate redox abnormalities in CYLD low-expressing tumors. HDACs are central players in the DNA damage signaling. We further confirmed that CYLD regulates radiation-induced DNA damage and repair response through inhibiting class I HDACs. Furthermore, CYLD mediates nasopharyngeal carcinoma cell radiosensitivity through class I HDACs. Thus, we identified the function of the CYLD-HDAC axis in radiotherapy and blocking HDACs by Chidamide can increase the sensitivity of cancer cells and tumors to radiation therapy both in vitro and in vivo. In addition, ChIP and luciferase reporter assays revealed that CYLD could be transcriptionally regulated by zinc finger protein 202 (ZNF202). Our findings offer novel insight into the function of CYLD in tumor and uncover important roles for CYLD-HDAC axis in radiosensitivity, which provide new molecular target and therapeutic strategy for tumor radiotherapy.
Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer
Authors: Wang Jiao , Zheng Fei , Wang Dandan , Yang Qing 
Published: January 2024

AbstractThere is a pressing need for innovative therapeutic strategies for patients with epithelial ovarian cancer (EOC). Previous studies have shown that UNC-51-like kinase 1 (ULK1), a serine/threonine kinase, is crucial in regulating cellular autophagy and mitophagy across various tumor types. However, the clinical implications, biological functions, and potential mechanisms of ULK1 in EOC remain poorly understood. This study demonstrates that ULK1 expression is upregulated in EOC tissue samples and EOC cell lines, with increased ULK1 expression correlating with poor prognosis. Functionally, overexpressed ULK1 enhances the proliferation and migration abilities of EOC cells both in vitro and in vivo. Mechanistically, ULK1 was identified as an m6A target of WTAP. WTAP-mediated m6A modification of ULK1 enhanced its mRNA stability in an IGF2BP3-dependent manner, leading to elevated ULK1 expression and enhanced mitophagy in EOC. In summary, our research reveals that the WTAP/IGF2BP3-ULK1 axis significantly influences protective mitophagy in EOC, contributing to its progression. Therefore, the regulatory mechanisms and biological function of ULK1 identify it as a potential molecular target for therapeutic intervention in EOC.
Carfilzomib relieves pancreatitis-initiated pancreatic ductal adenocarcinoma by inhibiting high-temperature requirement protein A1
Authors: Guo Fangyue , Tao Xufeng , Wu Yu , Dong Deshi , Zhu Yanna , Shang Dong , Xiang Hong 
Published: January 2024

AbstractPancreatitis is a crucial risk factor for pancreatic ductal adenocarcinoma (PDAC), and our previous study had proved high-temperature requirement protein A1 (HTRA1) exacerbates pancreatitis insult; however, the function and mechanism of HTRA1 in pancreatitis-initiated PDAC is still unclear. In the present paper, we clarified the expression of HTRA1 in PDAC using bioinformatics and immunohistochemistry of tissue chip, and found that HTRA1 is significantly upregulated in PDAC. Moreover, the proliferation, migration, invasion and adhesion of PANC-1 and SW1990 cells were promoted by overexpression of HTRA1, but inhibited by knockdown of HTRA1. Meanwhile, we found that HTRA1 arrested PANC-1 and SW1990 cells at G2/M phase. Mechanistically, HTRA1 interacted with CDK1 protein, and CDK1 inhibitor reversed the malignant phenotype of PANC-1 and pancreatitis-initiated PDAC activated by HTRA1 overexpression. Finally, we discovered a small molecule drug that can inhibit HTRA1, carfilzomib, which has been proven to inhibit the biological functions of tumor cells in vitro and intercept the progression of pancreatitis-initiated PDAC in vivo. In conclusion, the activation of HTRA1-CDK1 pathway promotes the malignant phenotype of tumor cells by blocking the cell cycle at the G2/M phase, thereby accelerating pancreatitis-initiated PDAC. Carfilzomib is an innovative candidate drug that can inhibit pancreatitis-initiated PDAC through targeted inhibition of HTRA1.
ARK5 enhances cell survival associated with mitochondrial morphological dynamics from fusion to fission in human multiple myeloma cells
Authors: Karnan Sivasundaram , Hanamura Ichiro , Ota Akinobu , Vu Lam Quang , Uchino Kaori , Horio Tomohiro , Murakami Satsuki , Mizuno Shohei , Rahman Md Lutfur , Wahiduzzaman Md , Hasan Muhammad Nazmul , Biswas Mrityunjoy , Hyodo Toshinori , Ito Hideaki , Suzuki Atsushi , Konishi Hiroyuki , Tsuzuki Shinobu , Hosokawa Yoshitaka , Takami Akiyoshi 
Published: January 2024

Abstract5′ adenosine monophosphate–activated protein kinase–related kinase 5 (ARK5) is involved in mitochondrial ATP production and associated with poor prognosis of multiple myeloma (MM). However, the molecular mechanisms of ARK5 in MM remain largely unknown. This study examined the pathogenic role of ARK5 in mitochondria by using genetically modified isogenic cell clones with or without ARK5 in human myeloma cell lines, KMS-11 and Sachi, which overexpress ARK5. The biallelic knockout of ARK5 (ARK5-KO) inhibited cell proliferation, colony formation, and migration with increased apoptosis. Mitochondrial fusion was enhanced in ARK5-KO cells, unlike in ARK5 wild-type (ARK5-WT) cells, which exhibited increased mitochondrial fission. Furthermore, ARK5-KO cells demonstrated a lower phosphorylated dynamin–related protein 1 at serine 616, higher protein expression of mitofusin-1 (MFN1) and MFN2, optic atrophy 1 with a lower level of ATP, and higher levels of lactate and reactive oxygen species than ARK5-WT cells. Our findings suggest that ARK5-enhanced myeloma cells can survive associated mitochondrial fission and activity. This study first revealed the relationship between ARK5 and mitochondrial morphological dynamics. Thus, our outcomes show novel aspects of mitochondrial biology of ARK5, which can afford a more advanced treatment approach for unfavorable MM expressing ARK5.
Identification of oleic acid as an endogenous ligand of GPR3
Authors: Xiong Yangjie , Xu Zhenmei , Li Xinzhi , Wang Yuqin , Zhao Jing , Wang Na , Duan Yaning , Xia Ruixue , Han Zhengbin , Qian Yu , Liang Jiale , Zhang Anqi , Guo Changyou , Inoue Asuka , Xia Yu , Chen Zheng , He Yuanzheng 
Published: January 2024

AbstractAlthough GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach (including cryo-electron microscopy), mass spectrometry analysis, and functional studies, we identify oleic acid (OA) as an endogenous ligand of GPR3. Our study reveals a hydrophobic tunnel within GPR3 that connects the extracellular side of the receptor to the middle of plasma membrane, enabling fatty acids to readily engage the receptor. Functional studies demonstrate that OA triggers downstream Gs signaling, whereas lysophospholipids fail to activate the receptor. Moreover, our research reveals that cold stimulation induces the secretion of OA in mice, subsequently activating Gs/cAMP/PKA signaling in brown adipose tissue. Notably, brown adipose tissues from Gpr3 knockout mice do not respond to OA during cold stimulation, reinforcing the significance of GPR3 in this process. Finally, we propose a “born to be activated and cold to enhance” model for GPR3 activation. Our study provides a starting framework for the understanding of GPR3 signaling in cold-stimulated thermogenesis.
Highly loaded bimetallic iron-cobalt catalysts for hydrogen release from ammonia
Authors: Chen Shilong , Jelic Jelena , Rein Denise , Najafishirtari Sharif , Schmidt Franz-Philipp , Girgsdies Frank , Kang Liqun , Wandzilak Aleksandra , Rabe Anna , Doronkin Dmitry E. , Wang Jihao , Friedel Ortega Klaus , DeBeer Serena , Grunwaldt Jan-Dierk , Schlögl Robert , Lunkenbein Thomas , Studt Felix , Behrens Malte 
Published: January 2024

AbstractAmmonia is a storage molecule for hydrogen, which can be released by catalytic decomposition. Inexpensive iron catalysts suffer from a low activity due to a too strong iron-nitrogen binding energy compared to more active metals such as ruthenium. Here, we show that this limitation can be overcome by combining iron with cobalt resulting in a Fe-Co bimetallic catalyst. Theoretical calculations confirm a lower metal-nitrogen binding energy for the bimetallic catalyst resulting in higher activity. Operando spectroscopy reveals that the role of cobalt in the bimetallic catalyst is to suppress the bulk-nitridation of iron and to stabilize this active state. Such catalysts are obtained from Mg(Fe,Co)2O4 spinel pre-catalysts with variable Fe:Co ratios by facile co-precipitation, calcination and reduction. The resulting Fe-Co/MgO catalysts, characterized by an extraordinary high metal loading reaching 74 wt.%, combine the advantages of a ruthenium-like electronic structure with a bulk catalyst-like microstructure typical for base metal catalysts.
Dorsal hippocampus to nucleus accumbens projections drive reinforcement via activation of accumbal dynorphin neurons
Authors: Ibrahim Khairunisa Mohamad , Massaly Nicolas , Yoon Hye-Jean , Sandoval Rossana , Widman Allie J. , Heuermann Robert J. , Williams Sidney , Post William , Pathiranage Sulan , Lintz Tania , Zec Azra , Park Ashley , Yu Waylin , Kash Thomas L. , Gereau Robert W. , Morón Jose A. 
Published: January 2024

AbstractThe hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the dorso-medial subregion of the NAc shell (dmNAcSh). Notably, dynorphin-containing neurons specifically contribute to dHPC-driven reinforcing behavior, even though both dmNAcSh dynorphin- and enkephalin-containing neurons are activated with dHPC stimulation. Our findings unveil a pathway governing reinforcement, advancing our understanding of the hippocampal circuity’s role in reward-seeking behaviors.
Harnessing synthetic active particles for physical reservoir computing
Authors: Wang Xiangzun , Cichos Frank 
Published: January 2024

AbstractThe processing of information is an indispensable property of living systems realized by networks of active processes with enormous complexity. They have inspired many variants of modern machine learning, one of them being reservoir computing, in which stimulating a network of nodes with fading memory enables computations and complex predictions. Reservoirs are implemented on computer hardware, but also on unconventional physical substrates such as mechanical oscillators, spins, or bacteria often summarized as physical reservoir computing. Here we demonstrate physical reservoir computing with a synthetic active microparticle system that self-organizes from an active and passive component into inherently noisy nonlinear dynamical units. The self-organization and dynamical response of the unit are the results of a delayed propulsion of the microswimmer to a passive target. A reservoir of such units with a self-coupling via the delayed response can perform predictive tasks despite the strong noise resulting from the Brownian motion of the microswimmers. To achieve efficient noise suppression, we introduce a special architecture that uses historical reservoir states for output. Our results pave the way for the study of information processing in synthetic self-organized active particle systems.
Supercurrent mediated by helical edge modes in bilayer graphene
Authors: Rout Prasanna , Papadopoulos Nikos , Peñaranda Fernando , Watanabe Kenji , Taniguchi Takashi , Prada Elsa , San-Jose Pablo , Goswami Srijit 
Published: January 2024

AbstractBilayer graphene encapsulated in tungsten diselenide can host a weak topological phase with pairs of helical edge states. The electrical tunability of this phase makes it an ideal platform to investigate unique topological effects at zero magnetic field, such as topological superconductivity. Here we couple the helical edges of such a heterostructure to a superconductor. The inversion of the bulk gap accompanied by helical states near zero displacement field leads to the suppression of the critical current in a Josephson geometry. Using superconducting quantum interferometry we observe an even-odd effect in the Fraunhofer interference pattern within the inverted gap phase. We show theoretically that this effect is a direct consequence of the emergence of helical modes that connect the two edges of the sample. The absence of such an effect at high displacement field, as well as in bare bilayer graphene junctions, supports this interpretation and demonstrates the topological nature of the inverted gap.
Risk of introduction and establishment of alien vertebrate species in transboundary neighboring areas
Authors: Zhang Qing , Wang Yanping , Liu Xuan 
Published: January 2024

AbstractCross-border neighboring areas could be particularly vulnerable to biological invasions due to short geographic distances and frequent interactions, although the invasion risk remains unevaluated worldwide. Here, based on global datasets of distributions of established alien vertebrates as well as vectors of introduction and establishment, we show that more than one-third of the world’s transboundary neighboring areas are facing high invasion risk of alien vertebrates, especially in Europe, North America, South Asia, and Southeast Asia. The most important predictors of high introduction and establishment risk are bilateral trade, habitat disturbance and the richness of established alien vertebrates. Interestingly, we found that border fences may have limited effects in reducing the risk, as only 7.9% of border fences spatially overlap with hotspots of biological invasion even in the Eurasia areas (13.7% overlap) where physical border barriers are mainly located. We therefore recommend the implementation of immediate and proactive prevention and control measures to cope with cross-border invasions in response to continued globalization.
Effect of solid-electrolyte pellet density on failure of solid-state batteries
Authors: Diallo Mouhamad S. , Shi Tan , Zhang Yaqian , Peng Xinxing , Shozib Imtiaz , Wang Yan , Miara Lincoln J. , Scott Mary C. , Tu Qingsong Howard , Ceder Gerbrand 
Published: January 2024

AbstractDespite the potentially higher energy density and improved safety of solid-state batteries (SSBs) relative to Li-ion batteries, failure due to Li-filament penetration of the solid electrolyte and subsequent short circuit remains a critical issue. Herein, we show that Li-filament growth is suppressed in solid-electrolyte pellets with a relative density beyond ~95%. Below this threshold value, however, the battery shorts more easily as the density increases due to faster Li-filament growth within the percolating pores in the pellet. The microstructural properties (e.g., pore size, connectivity, porosity, and tortuosity) of $$75\%{{{{{\rm{L}}}}}}{{{{{{\rm{i}}}}}}}_{2}{{{{{\rm{S}}}}}}-25\%{{{{{{\rm{P}}}}}}}_{2}{{{{{{\rm{S}}}}}}}_{5}$$
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with various relative densities are quantified using focused ion beam–scanning electron microscopy tomography and permeability tests. Furthermore, modeling results provide details on the Li-filament growth inside pores ranging from 0.2 to 2 μm in size. Our findings improve the understanding of the failure modes of SSBs and provide guidelines for the design of dendrite-free SSBs.