bluuebunny/crossref_metadata_2025_split huggingface dataset:
A tripartite microbial co-culture system for de novo biosynthesis of diverse plant phenylpropanoids
Authors: Brooks Sierra M. , Marsan Celeste , Reed Kevin B. , Yuan Shuo-Fu , Nguyen Dustin-Dat , Trivedi Adit , Altin-Yavuzarslan Gokce , Ballinger Nathan , Nelson Alshakim , Alper Hal S. 
Published: July 2023

AbstractPlant-derived phenylpropanoids, in particular phenylpropenes, have diverse industrial applications ranging from flavors and fragrances to polymers and pharmaceuticals. Heterologous biosynthesis of these products has the potential to address low, seasonally dependent yields hindering ease of widespread manufacturing. However, previous efforts have been hindered by the inherent pathway promiscuity and the microbial toxicity of key pathway intermediates. Here, in this study, we establish the propensity of a tripartite microbial co-culture to overcome these limitations and demonstrate to our knowledge the first reported de novo phenylpropene production from simple sugar starting materials. After initially designing the system to accumulate eugenol, the platform modularity and downstream enzyme promiscuity was leveraged to quickly create avenues for hydroxychavicol and chavicol production. The consortia was found to be compatible with Engineered Living Material production platforms that allow for reusable, cold-chain-independent distributed manufacturing. This work lays the foundation for further deployment of modular microbial approaches to produce plant secondary metabolites.
3D printing titanium grid scaffold facilitates osteogenesis in mandibular segmental defects
Authors: Li Yongfeng , Liu Huawei , Wang Chao , Yan Rongzeng , Xiang Lei , Mu Xiaodan , Zheng Lingling , Liu Changkui , Hu Min 
Published: July 2023

AbstractBone fusion of defect broken ends is the basis of the functional reconstruction of critical maxillofacial segmental bone defects. However, the currently available treatments do not easily achieve this goal. Therefore, this study aimed to fabricate 3D-printing titanium grid scaffolds, which possess sufficient pores and basic biomechanical strength to facilitate osteogenesis in order to accomplish bone fusion in mandibular segmental bone defects. The clinical trial was approved and supervised by the Medical Ethics Committee of the Chinese PLA General Hospital on March 28th, 2019 (Beijing, China. approval No. S2019–065–01), and registered in the clinical trials registry platform (registration number: ChiCTR2300072209). Titanium grid scaffolds were manufactured using selective laser melting and implanted in 20 beagle dogs with mandibular segmental defects. Half of the animals were treated with autologous bone chips and bone substances incorporated into the scaffolds; no additional filling was used for the rest of the animals. After 18 months of observation, radiological scanning and histological analysis in canine models revealed that the pores of regenerated bone were filled with titanium grid scaffolds and bone broken ends were integrated. Furthermore, three patients were treated with similar titanium grid scaffold implants in mandibular segmental defects; no mechanical complications were observed, and similar bone regeneration was observed in the reconstructed patients’ mandibles in the clinic. These results demonstrated that 3D-printing titanium grid scaffolds with sufficient pores and basic biomechanical strength could facilitate bone regeneration in large-segment mandibular bone defects.
A TLR7/8 agonist increases efficacy of anti-fentanyl vaccines in rodent and porcine models
Authors: Crouse Bethany , Miller Shannon M. , Muelken Peter , Hicks Linda , Vigliaturo Jennifer R. , Marker Cheryl L. , Guedes Alonso G. P. , Pentel Paul R. , Evans Jay T. , LeSage Mark G. , Pravetoni Marco 
Published: July 2023

AbstractOpioid use disorders (OUD) and overdose are public health threats worldwide. Widespread access to highly potent illicit synthetic opioids such as fentanyl is driving the recent rise in fatal overdoses. Vaccines containing fentanyl-based haptens conjugated to immunogenic carrier proteins offer a long-lasting, safe, and cost-effective strategy to protect individuals from overdose upon accidental or deliberate exposure to fentanyl and its analogs. Prophylactic or therapeutic active immunization with an anti-fentanyl vaccine induces the production of fentanyl-specific antibodies that bind the drug in the blood and prevent its distribution to the brain, which reduces its reinforcing effects and attenuates respiratory depression and bradycardia. To increase the efficacy of a lead anti-fentanyl vaccine, this study tested whether the incorporation of synthetic toll-like receptor (TLR) 4 and TLR7/8 agonists as vaccine adjuvants would increase vaccine efficacy against fentanyl challenge, overdose, and self-administration in either rats or Hanford miniature pigs. Formulation of the vaccine with a nucleolipid TLR7/8 agonist enhanced its immunogenicity and efficacy in preventing fentanyl-induced respiratory depression, analgesia, bradycardia, and self-administration in either rats or mini-pigs. These studies support the use of TLR7/8 adjuvants in vaccine formulations to improve their clinical efficacy against OUD and potentially other substance use disorders (SUD).
Controlling the Solo12 quadruped robot with deep reinforcement learning
Authors: Aractingi Michel , Léziart Pierre-Alexandre , Flayols Thomas , Perez Julien , Silander Tomi , Souères Philippe 
Published: July 2023

AbstractQuadruped robots require robust and general locomotion skills to exploit their mobility potential in complex and challenging environments. In this work, we present an implementation of a robust end-to-end learning-based controller on the Solo12 quadruped. Our method is based on deep reinforcement learning of joint impedance references. The resulting control policies follow a commanded velocity reference while being efficient in its energy consumption and easy to deploy. We detail the learning procedure and method for transfer on the real robot. We show elaborate experiments. Finally, we present experimental results of the learned locomotion on various grounds indoors and outdoors. These results show that the Solo12 robot is a suitable open-source platform for research combining learning and control because of the easiness in transferring and deploying learned controllers.
Research on surrogate model of dam numerical simulation with multiple outputs based on adaptive sampling
Authors: Liang Jiaming , Li Zhanchao , Pan Litan , Khailah Ebrahim Yahya , Sun Linsong , Lu Weigang 
Published: July 2023

AbstractDam numerical simulation is an important method to research the dam structural behavior, but it often takes a lot of time for calculation when facing problems that require many simulations, such as structural parameter back analysis. The surrogate model is widely used as a technology to reduce computational cost. Although various methods have been widely investigated, there are still problems in designing the surrogate model's optimal Design of Experiments (DoE). In addition, most of the current DoE focuses on establishing a single-output problem. Designing a reasonable DoE for high-dimensional outputs is also a problem that needs to be solved. Based on the above issues, this research proposes a sequential surrogate model based on the radial basis function model (RBFM) with multi-outputs adaptive sampling. The benchmark function demonstrates the applicability of the proposed method to single-input & multi-outputs and multi-inputs & multi-outputs problems. Then, this method is applied to establishing a surrogate model for dam numerical simulation with multi-outputs. The result demonstrates that the proposed technique can be sampled adaptively and samples can be targeted based on the function form of the surrogate model, which significantly reduces the required sampling and calculation cost.
Knockdown of protein interacting with C α kinase 1 aggravates sepsis-induced acute liver injury by regulating the TLR4/NF-κB pathway
Authors: Wang Huijun , Ma Ting , Bao Qianqian , Zhu Lijun , Ying Tingting , Yu Yulong 
Published: July 2023

AbstractAcute liver injury (ALI) may manifest at any phase of sepsis, yet an explicit therapeutic approach remains elusive. In this study, LPS and cecum ligation and puncture (CLP) were utilized to establish an inflammatory cell model and a murine model of sepsis-induced liver injury, respectively, aiming to explore the potential protective effect of protein interacting with C α kinase 1 (PICK1) on sepsis-induced ALI and its underlying mechanisms. In both the cell supernatant and the murine whole blood, the concentrations of inflammatory factors were quantified by ELISA, while the protein and mRNA expressions of PICK1, cleaved-PARP-1, caspase1, TLR4, IκBα, and NF-κB were assessed via western blot and qRT-PCR. The outcomes revealed that the knockdown of PICK1 increased the levels of inflammatory factors and apoptosis, alongside activation of TLR4/NF-κB signaling pathway-related factors in both in vivo and in vitro models. Moreover, the murine liver samples were subjected to Hematoxylin–Eosin (HE) staining for assessment of histopathological morphology. The HE staining and liver injury scoring results manifested a markedly exacerbated hepatic damage in PICK1 knockout mice as compared to WT mice following CLP. Furthermore, the liver macrophages were isolated from murine livers, and the expression and activity of the factors associated with the TLR4/NF-κB signaling pathway were verified through RT-qPCR and western blot, and EMSA assay demonstrated an augmented NF-κB activity subsequent to PICK1 knockout. Finally, the expression and localization of PICK1 in macrophages were further scrutinized via immunofluorescence, and the interaction between PICK1 and TLR4 was identified through co-immunoprecipitation. In conclusion, the knockdown of PICK1 appeared to modulate inflammatory factors by activating the TLR4/NF-κB signaling pathway, thereby exacerbating hepatic damage induced by sepsis.
Expandable ELAST for super-resolution imaging of thick tissue slices using a hydrogel containing charged monomers
Authors: La Woonggi , Seo Junyoung , Heo Eunseok , Chang Jae-Byum 
Published: July 2023

AbstractHydrogels have been utilized extensively as a material for retaining position information in tissue imaging procedures, such as tissue clearing and super-resolution imaging. Immunostaining thick biological tissues, however, poses a bottleneck that restricts sample size. The recently developed technique known as entangled link-augmented stretchable tissue-hydrogel (ELAST) accelerates the immunostaining process by embedding specimens in long-chain polymers and stretching them. A more advanced version of ELAST, magnifiable entangled link-augmented stretchable tissue-hydrogel (mELAST), achieves rapid immunostaining and tissue expansion by embedding specimens in long-chain neutral polymers and subsequently hydrolyzing them. Building on these techniques, we introduce a variant of mELAST called ExELAST. This approach uses charged monomers to stretch and expand tissue slices. Using ExELAST, we first tested two hydrogel compositions that could permit uniform expansion of biological specimens. Then, we apply the tailored hydrogel to the 500-μm-thick mouse brain slices and demonstrated that they can be stained within two days and imaged with a resolution below the diffraction limit of light.
Climate-driven marmot-plague dynamics in Mongolia and China
Authors: Xu Lei , Wang Qian , Yang Ruifu , Ganbold Dalantai , Tsogbadrakh Nyamdorj , Dong Kaixing , Liu Min , Altantogtokh Doniddemberel , Liu Qiyong , Undrakhbold Sainbileg , Boldgiv Bazartseren , Liang Wannian , Stenseth Nils Chr. 
Published: July 2023

AbstractThe incidence of plague has rebounded in the Americas, Asia, and Africa alongside rapid globalization and climate change. Previous studies have shown local climate to have significant nonlinear effects on plague dynamics among rodent communities. We analyzed an 18-year database of plague, spanning 1998 to 2015, in the foci of Mongolia and China to trace the associations between marmot plague and climate factors. Our results suggested a density-dependent effect of precipitation and a geographic location-dependent effect of temperature on marmot plague. That is, a significantly positive relationship was evident between risk of plague and precipitation only when the marmot density exceeded a certain threshold. The geographical heterogeneity of the temperature effect and the contrasting slopes of influence for the Qinghai-Tibet Plateau (QTP) and other regions in the study (nQTP) were primarily related to diversity of climate and landscape types.
Transient simulation of laser ablation based on Monte Carlo light transport with dynamic optical properties model
Authors: Shimojo Yu , Sudo Kazuma , Nishimura Takahiro , Ozawa Toshiyuki , Tsuruta Daisuke , Awazu Kunio 
Published: July 2023

AbstractLaser ablation is a minimally invasive therapeutic technique to denature tumors through coagulation and/or vaporization. Computational simulations of laser ablation can evaluate treatment outcomes quantitatively and provide numerical indices to determine treatment conditions, thus accelerating the technique’s clinical application. These simulations involve calculations of light transport, thermal diffusion, and the extent of thermal damage. The optical properties of tissue, which govern light transport through the tissue, vary during heating, and this affects the treatment outcomes. Nevertheless, the optical properties in conventional simulations of coagulation and vaporization remain constant. Here, we propose a laser ablation simulation based on Monte Carlo light transport with a dynamic optical properties (DOP) model. The proposed simulation is validated by performing optical properties measurements and laser irradiation experiments on porcine liver tissue. The DOP model showed the replicability of the changes in tissue optical properties during heating. Furthermore, the proposed simulation estimated coagulation areas that were comparable to experimental results at low-power irradiation settings and provided more than 2.5 times higher accuracy when calculating coagulation and vaporization areas than simulations using static optical properties at high-power irradiation settings. Our results demonstrate the proposed simulation’s applicability to coagulation and vaporization region calculations in tissue for retrospectively evaluating the treatment effects of laser ablation.
Identification of c-Met as a novel target of γ-glutamylcyclotransferase
Authors: Saito Yumiko , Taniguchi Keiko , Ii Hiromi , Horinaka Mano , Kageyama Susumu , Nakata Susumu , Ukimura Osamu , Sakai Toshiyuki 
Published: July 2023

Abstractγ-Glutamylcyclotransferase (GGCT) is highly expressed in multiple types of cancer tissues and its knockdown suppresses the growth of cancer cells in vitro and in vivo. Although GGCT is a promising target for cancer therapy, the mechanisms underlying the antitumor effects remain unclear. The knockdown of GGCT inhibited the MEK-ERK pathway, and activated the tumor suppressor retinoblastoma gene (RB) at the protein level in cancer cell lines. c-Met was down-regulated by the knockdown of GGCT in cancer cells and its overexpression attenuated the dephosphorylation of RB and cell cycle arrest induced by the knockdown of GGCT in lung cancer A549 cells. STAT3 is a transcription factor that induces c-Met expression. STAT3 phosphorylation and its nuclear expression level were decreased in GGCT-depleted A549 and prostate cancer PC3 cells. The simultaneous knockdown of AMPK and GGCT restored the down-regulated expression of c-Met, and attenuated the dephosphorylation of STAT3 and MEK-ERK-RB induced by the knockdown of GGCT in PC3 cells. An intraperitoneal injection of a GGCT inhibitor decreased c-Met protein expression in a mouse xenograft model of PC3 cells. These results suggest that the knockdown of GGCT activates the RB protein by inhibiting the STAT3-c-Met-MEK-ERK pathway via AMPK activation.
Molecular features driving condensate formation and gene expression by the BRD4-NUT fusion oncoprotein are overlapping but distinct
Authors: Kosno Martyna , Currie Simon L. , Kumar Ashwani , Xing Chao , Rosen Michael K. 
Published: July 2023

AbstractAberrant formation of biomolecular condensates has been proposed to play a role in several cancers. The oncogenic fusion protein BRD4-NUT forms condensates and drives changes in gene expression in Nut Carcinoma. Here we sought to understand the molecular elements of BRD4-NUT and its associated histone acetyltransferase (HAT), p300, that promote these activities. We determined that a minimal fragment of NUT (MIN) in fusion with BRD4 is necessary and sufficient to bind p300 and form condensates. Furthermore, a BRD4-p300 fusion protein also forms condensates and drives gene expression similarly to BRD4-NUT(MIN), suggesting the p300 fusion may mimic certain features of BRD4-NUT. The intrinsically disordered regions, transcription factor-binding domains, and HAT activity of p300 all collectively contribute to condensate formation by BRD4-p300, suggesting that these elements might contribute to condensate formation by BRD4-NUT. Conversely, only the HAT activity of BRD4-p300 appears necessary to mimic the transcriptional profile of cells expressing BRD4-NUT. Our results suggest a model for condensate formation by the BRD4-NUT:p300 complex involving a combination of positive feedback and phase separation, and show that multiple overlapping, yet distinct, regions of p300 contribute to condensate formation and transcriptional regulation.
A nystagmus extraction system using artificial intelligence for video-nystagmography
Authors: Lee Yerin , Lee Sena , Han Junghun , Seo Young Joon , Yang Sejung 
Published: July 2023

AbstractBenign paroxysmal positional vertigo (BPPV), the most common vestibular disorder, is diagnosed by an examiner changing the posture of the examinee and inducing nystagmus. Among the diagnostic methods used to observe nystagmus, video-nystagmography has been widely used recently because it is non-invasive. A specialist with professional knowledge and training in vertigo diagnosis is needed to diagnose BPPV accurately, but the ratio of vertigo patients to specialists is too high, thus necessitating the need for automated diagnosis of BPPV. In this paper, a convolutional neural network-based nystagmus extraction system, ANyEye, optimized for video-nystagmography data is proposed. A pupil was segmented to track the exact pupil trajectory from real-world data obtained during field inspection. A deep convolutional neural network model was trained with the new video-nystagmography dataset for the pupil segmentation task, and a compensation algorithm was designed to correct pupil position. In addition, a slippage detection algorithm based on moving averages was designed to eliminate the motion artifacts induced by goggle slippage. ANyEye outperformed other eye-tracking methods including learning and non-learning-based algorithms with five-pixel error detection rate of 91.26%.
A novel spherical ultrasonic motor with wire stators and measuring torque and preload via a new method
Authors: Jahantab Seyed Hassan , Hojjat Yousef , Ghavami Namin Behzad , Shirkosh Mohammad 
Published: July 2023

AbstractThe present study introduces a multi-degree-of-freedom (MDOF) ultrasonic motor, which is capable of driving a spherical rotor using spiral wire stators and a piezoelectric stack actuator. Wire stators and piezoelectric stack actuators enable the proposed motor to be smaller and simpler, lower in power consumption, and have different modes at different frequencies. In this motor, two wire stators are used to drive the spherical rotor and rotate it in different directions. The eigenfrequency and frequency domain analyses were carried out using the finite element method (FEM) to evaluate the MDOF capability of the motor in different vibration modes. It has been demonstrated that the piezoelectric stack actuator can provide MDOF motions through its vibration modes. The resonant frequency obtained by the frequency domain approach agreed with the impedance analyzer test. Rotational speed, torque, and preload force were experimentally investigated. Using shear stress caused by viscous fluid in contact with the spherical rotor, a new torque calculation method was developed. Based on the buoyancy force exerted on the immersed rotor, the preload force was measured. The experimental results indicated that the maximum rotational speed of the spherical rotor was 306 rpm, and the maximum torque was 4.7 μN m.
Schwann cell-encapsulated chitosan-collagen hydrogel nerve conduit promotes peripheral nerve regeneration in rodent sciatic nerve defect models
Authors: Takeya Hiroaki , Itai Shun , Kimura Hiroo , Kurashina Yuta , Amemiya Tsuyoshi , Nagoshi Narihito , Iwamoto Takuji , Sato Kazuki , Shibata Shinsuke , Matsumoto Morio , Onoe Hiroaki , Nakamura Masaya 
Published: July 2023

AbstractChitosan has various tissue regeneration effects. This study was designed to investigate the nerve regeneration effect of Schwann cell (SC)-encapsulated chitosan-collagen hydrogel nerve conduit (CCN) transplanted into a rat model of sciatic nerve defect. We prepared a CCN consisting of an outer layer of chitosan hydrogel and an inner layer of collagen hydrogel to encapsulate the intended cells. Rats with a 10-mm sciatic nerve defect were treated with SCs encapsulated in CCN (CCN+), CCN without SCs (CCN−), SC-encapsulated silicone tube (silicone+), and autologous nerve transplanting (auto). Behavioral and histological analyses indicated that motor functional recovery, axonal regrowth, and myelination of the CCN+ group were superior to those of the CCN− and silicone+ groups. Meanwhile, the CCN− and silicone+ groups showed no significant differences in the recovery of motor function and nerve histological restoration. In conclusion, SC-encapsulated CCN has a synergistic effect on peripheral nerve regeneration, especially axonal regrowth and remyelination of host SCs. In the early phase after transplantation, SC-encapsulated CCNs have a positive effect on recovery. Therefore, using SC-encapsulated CCNs may be a promising approach for massive peripheral nerve defects.
Seaweed extract and arbuscular mycorrhiza co-application affect the growth responses and essential oil composition of Foeniculum vulgare L.
Authors: Rasouli Farzad , Nasiri Yousef , Hassanpouraghdam Mohammad Bagher , Asadi Mohammad , Qaderi Taher , Trifa Amini , Strzemski Maciej , Dresler Sławomir , Szczepanek Małgorzata 
Published: July 2023

AbstractThe influence of arbuscular mycorrhiza fungi (AMF) inoculation, seaweed extract (SWE) foliar use, and their co-applications were evaluated on the growth-associated traits, antioxidant potential, essential oil profile, and the nutrients content of fennel plants. A factorial experiment was conducted as a completely randomized design with two factors and four replications in the greenhouse. The factors were: AMF inoculation (not inoculated and inoculated with 5 g kg−1) and SWE foliar application (0, 0.5, 1.5, or 3 g L−1). The highest root colonization percentage was recorded in plants treated with AMF + 3 g L−1 of SWE. The top recorded plant height, leaf number, leaf dry weight, biomass, thousand seed weight (TSW), total soluble proteins and total soluble carbohydrates content, antioxidant activity, and essential oil content belonged to AMF + 3 g L−1 of SWE. Furthermore, the co-application of AMF + SWE resulted in a considerable enhancement of the photosynthetic pigments content and, in N, P, K, Fe, Zn, and Mn contents in the shoots and roots. The GC-FID and GC–MS analysis revealed that (E)-anethole (73.28–76.18%), fenchone (5.94–8.26%), limonene (4.64–6.58%), methyl chavicol (2.91–3.18%), and (Z)-β-ocimene (1.36–2.01%) were the principal essential oil constituents. The top (E)-anethole and fenchone contents were obtained by AMF + SWE. Altogether, the simultaneous application of AMF and SWE could be introduced as an environment-friendly strategy to reach reliable growth responses, especially in fennel plants' enriched with some precious essential oil constituents.