REVIEW | doi:10.20944/preprints202308.2151.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Medicinal and edible plants; cell cultures; cell fusion; somatic hybridization; artificial polyploidy induction; cell engineering
Online: 31 August 2023 (07:52:44 CEST)
With worsening environmental degradation and increasing international demand for human health, plant cell based technology will be more important. The aim of this review is to give an overview regarding key points of current progress and development trend of nature medical and edible plants from the framework of whole plant cell engineering including cell cultures, cell fusion and cell splitting derived biotechnology. Here we sum up three main application trends of medical plants cell cultures covering industrial output, technology upgrading and potential resource development. We also provide classification and typification insights to summarize the development of somatic hybridization in cereal, vegetables crops and other medicinal and edible plants as well as application of artificial polyploidy induction in major medicinal herbs. Development medicinal and edible homologous plants based on modern plant cell engineering will bring us a promising future.
ARTICLE | doi:10.20944/preprints202309.1773.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: geospatial entities; annotation system; deep learning; BiLSTM+CRF+AGG model; active Learning; human-assisted
Online: 26 September 2023 (13:59:37 CEST)
When analyzing user geospatial information through deep learning methods, it is typically necessary to annotate existing geospatial data. Currently, manual annotation methods are commonly employed, suffering from issues related to low efficiency and accuracy. This design is based on the TensorFlow deep learning framework and first realizes the BiLSTM+CRF+AGG deep learning model. Among the models, AGG is the aggregation layer, which is introduced to solve the problem of solid particle size equilibrium. Secondly, based on the characteristics of original data and professional data, an automatic labeling algorithm is proposed. The algorithm first preprocesses the acquired original data set and professional data set, The most valuable unlabeled data set which can make the training model converge quickly is selected from the original data set as the target data set. Sort the target data set based on preset rules and set annotation parameters for the sorted target data set. Based on the set annotation parameters, the corpus is synthesized and used as the annotation result. Thirdly, based on the active learning strategy, a manual annotation auxiliary scheme is proposed, and an Excel generation module that is convenient for manual annotation correction is designed and developed to further improve the efficiency and quality of annotation through iterative processing. The combination of the BiLSTM+CRF+AGG deep learning model and high-quality annotation can accurately identify non-standard, incomplete, or even incorrect geographical information entities. This annotation method has found successful practical application within the context of the research project and has been granted an invention patent.
ARTICLE | doi:10.20944/preprints202306.0364.v2
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Chinese address parsing; low-resource scenarios; In-context learning; GPT; BERT; k-nearest neighbors
Online: 9 June 2023 (04:28:59 CEST)
Address parsing is a crucial task in natural language processing, particularly for Chinese addresses. The complex structure and semantic features of Chinese addresses present challenges due to their inherent ambiguity. Additionally, different task scenarios require varying levels of granularity in address components, further complicating the parsing process. To address these challenges and adapt to low-resource environments, we propose CapICL, a novel Chinese address parsing model based on the In-Context Learning (ICL) framework. CapICL leverages a sequence generator, regular expression matching, BERT semantic similarity computation, and GPT modeling to enhance parsing accuracy by incorporating contextual information. We construct the sequence generator using a small annotated dataset, capturing distribution patterns and boundary features of address types to model address structure and semantics, mitigating interference from unnecessary variations. We introduce the REB-KNN algorithm, which selects similar samples for ICL-based parsing using regular expression matching and BERT semantic similarity computation. The selected samples, raw text, and explanatory text are combined to form prompts, and inputted into the GPT model for prediction and address parsing. Experimental results demonstrate significant achievements of CapICL in low-resource environments, reducing dependency on annotated data and computational resources. Our model's effectiveness, adaptability, and broad application potential are validated, showcasing its positive impact in natural language processing and geographical information systems.
REVIEW | doi:10.20944/preprints202205.0359.v1
Subject: Social Sciences, Behavior Sciences Keywords: emotion；conceptualization；interoception；afferent；efferent
Online: 26 May 2022 (08:57:02 CEST)
Empirical and theoretical advances in human neuroscience have led to a reappraisal of the relationships between mind, brain and body, the implications of which are particularly relevant to understanding emotions, which is revealed to be embodied owing to the facts that they are on the one hand primarily arise from the internal bodily states controlled by interoceptive system, on the other they give rise to physiological reactions and physical action evoked by autonomic nervous system. More specifically, when considering the ‘embodied mind’ (i.e., how mental processes are inescapably contextualized by their location within the body), the brain, instead of the ‘master’ of the body, is increasingly revealed to function as the ‘servant’, with its primary goal to maintain the body’s homeostatic integrity. This is achieved through the control of interoceptive information concerning body’s physiological state, initially as ‘simple’ organ-level homeostatic reflexes and then through higher-order coordination across organ-systems allowing ‘allostatic policies’ to predict and maintain future health of the integrated whole ‘biological-self’. In this context, motivational and emotional feelings arise from interoceptive signals that accompany (motivational and emotional) internally-directed physiological responses, and externally-directed behaviors. Emotion concepts are thus the categorized embodied outcomes of bidirectional brain-body interactions and may arguably be differentiated into afferent interoceptive processes, i.e., from body to brain, and efferent/autonomic processes, i.e., from brain to body. When comparing emotion words used in Chinese and English languages, afferent/interoceptive processes seem to dominate conceptualization of embodied emotions in Chinese, while the efferent processes feature more commonly in English. The presence of distinct conceptual systems relating to emotions may, according to the linguistic relativity hypothesis as well as the theory of constructed emotion, significantly shape the distinct values and ‘national character’ of Chinese and English–speaking cultures. Correspondingly, it is argued that, in the expression of affective traits, Chinese-speaking people are biased towards being more receptive, reflective and adaptive, whereas native English speakers may tend to be more reactive, proactive and interactive. These patterns also encompass functions historically ascribed to bodily organs by traditional Chinese and ancient Greek medicine.
ARTICLE | doi:10.20944/preprints201810.0356.v2
Subject: Environmental And Earth Sciences, Geophysics And Geology Keywords: higher-mode surface waves; dispersion curves; morphological component analysis; Radon transform
Online: 17 October 2018 (09:00:53 CEST)
Extraction of high-resolution surface waves is essential in surface-wave survey. Because reflections usually interfere with surface waves on X component in a multicomponent seismic exploration, it is difficult to extract dispersion curves of surface waves. The situation goes more serious when the frequencies and velocities of higher-mode surface waves are close to those of PS-waves. A method for surface-wave extraction is proposed based on the morphological differences between reflections and surface waves. Frequency-domain high-resolution linear Radon transform (LRT) and time-domain high-resolution hyperbolic Radon transform (HRT) are used to represent surface waves and reflections respectively. Then, the sparse representation problem based on the morphological component analysis (MCA) is built and optimally solved to obtain high-fidelity surface waves. An advantage of our method is its ability to extract surface waves when their frequencies and velocities are close to those of reflections. Furthermore, results of synthetic and field examples confirm that the proposed method can attenuate the distortion of surface-wave dispersive energy caused by reflections, which contributes to extracting accurate dispersion curves.
ARTICLE | doi:10.20944/preprints201810.0038.v1
Subject: Engineering, Electrical And Electronic Engineering Keywords: physical layer security; MIMO interference channel; relay; total MSE; IoT
Online: 3 October 2018 (08:14:26 CEST)
In this paper, we first investigate secure communications for a two-hop interference relay system in the wireless Internet of Things (IoT), where K source-destination pairs communicate in the presence of an eavesdropper. Explicitly, we jointly design source, relay and destination matrices upon minimizing total mean-squared error (MSE) of all legitimate destinations while keeping the MSE at eavesdropper above a certain threshold. We illuminate that the joint design of the source, relay and destination matrices subject to both secrecy and transmit power constraints. More specifically, we proposed an efficient iterative distributed algorithm to simplify the process of the joint design for optimal source, relay and destination matrices. Furthermore, the convergence of the iterative distributed algorithm is described. Additionally, the performances of the proposed algorithm, including both its secrecy rate and MSE, are characterized with the aid of simulation results. We demonstrate that our proposed algorithm outperforms the traditional approach. As a benefit, secure communications can be guaranteed by using the proposed algorithm for the multiple input multiple output (MIMO) interference relay IoT network in the presence of an eavesdropper.
ARTICLE | doi:10.20944/preprints202109.0180.v1
Subject: Engineering, Industrial And Manufacturing Engineering Keywords: point cloud registration; template point cloud; multiple partial point cloud; deep learning
Online: 10 September 2021 (10:26:10 CEST)
With the advancement of photoelectric technology and computer image processing technology, the visual measurement method based on point clouds is gradually applied to the 3D measurement of large workpieces. Point cloud registration is a key step in 3D measurement, and its registration accuracy directly affects the accuracy of 3D measurements. In this study, we designed a novel MPCR-Net for multiple partial point cloud registration networks. First, an ideal point cloud was extracted from the CAD model of the workpiece and was used as the global template. Next, a deep neural network was used to search for the corresponding point groups between each partial point cloud and the global template point cloud. Then, the rigid body transformation matrix was learned according to these correspondence point groups to realize the registration of each partial point cloud. Finally, the iterative closest point algorithm was used to optimize the registration results to obtain a final point cloud model of the workpiece. We conducted point cloud registration experiments on untrained models and actual workpieces, and by comparing them with existing point cloud registration methods, we verified that the MPCR-Net could improve the accuracy and robustness of the 3D point cloud registration.
ARTICLE | doi:10.20944/preprints201907.0142.v3
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: glaucoma; tissue engineering; trabecular meshwork; outflow facility
Online: 8 December 2020 (10:09:17 CET)
Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye’s anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM) at the entrance of the eye’s drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered anterior segment eye culture model. We hypothesized that repopulation of a decellularized TM with non-native TM cells could restore aspects of normal TM. The decellularization protocol removed all cells and debris while preserving the ECM. Seeded cells localized to the TM region and progressively infiltrated the meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After a perfusion rate increase challenge, tissue-engineered cultures reestablished normal IOPs (reseeded = 13.7±0.4 mmHg, decellularized = 35.2±2.2 mmHg, p < 0.0001). eGFP expressing CrFK control cells caused a high and unstable IOP (27.0±6.2 mmHg). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. Tissue-engineered organs demonstrated similarities to native tissues and may reduce the need for scarce donor globes in outflow research.
ARTICLE | doi:10.20944/preprints202310.1311.v1
Subject: Chemistry And Materials Science, Polymers And Plastics Keywords: two-dimensional materials; cotton fabric; phenolic resin; friction and wear; molecular dynamics
Online: 20 October 2023 (08:09:09 CEST)
In this study, cotton fabric reinforced phenolic resin (CPF) composites were modified by adding four two-dimensional fillers: graphitic carbon nitride (g-C3N4), graphite (Gr), molybdenum disulfide (MoS2), and hexagonal boron nitride (h-BN). The tribological properties of these modified materials were investigated under dry friction and water lubrication conditions. CPF/ Gr composite exhibits significantly better tribological performance than the other three fillers modified CPF composites under dry friction, with a 24% reduction in friction coefficient and a 78% reduction in wear rate compared to unmodified CPF composite. Under water lubrication conditions, all four fillers did not significantly alter the friction coefficient of the CPF composite. However, except for an excessive amount of Gr, the other three fillers can reduce the wear rate. Particularly, in the case of 10% MoS2 content, the wear rate decreased by 56%. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were employed for the analysis of the morphology and composition of the transfer films. Additionally, molecular dynamics (MD) simulations were conducted to investigate the adsorption effects of Gr, MoS2, and PF on the counterpart surface under both dry friction and water lubrication conditions. The difference in the adsorption capacity of Gr and MoS2 on the counterpart, as well as the resulting formation of transfer films, accounts for the variation in tribological behavior between CPF/Gr and CPF/MoS2 composites. By combining the lubrication properties of MoS2 and Gr under dry friction and water lubrication conditions, using them as co-fillers can achieve a synergistic lubrication effect.
ARTICLE | doi:10.20944/preprints201803.0219.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: pigmentary glaucoma; pigment dispersion; intraocular pressure; trabecular meshwork; cytoskeleton; phagocytosis; gene expression microarray; signal pathway
Online: 27 March 2018 (05:22:15 CEST)
Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.
ARTICLE | doi:10.20944/preprints201807.0131.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: pigmentary glaucoma; ROCK kinase inhibitor; RKI-1447; trabecular meshwork; phagocytosis; cytoskeleton
Online: 9 July 2018 (11:27:28 CEST)
Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/mL for 48 hours before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.
ARTICLE | doi:10.20944/preprints201802.0026.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: pig eye perfusion model; pigmentary glaucoma; ocular hypertension; ocular hypotension; phagocytosis; rho-kinase inhibitor
Online: 5 February 2018 (03:39:57 CET)
Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods: Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67 × 107 pigment particles/mL) for 48 hours before being subjected to the RKI-1447 (n = 16) or the vehicle control (n = 12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis. Results: Compared to the baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 exhibited no apparent changes in the micro- or macroscopic appearance, including histology. Primary TM cells exposed to RKI-1447 showed a significant disruption of the actin cytoskeleton both in the presence and absence of pigment exposure (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI reversed. Conclusions: RKI-1447 is a novel ROCK inhibitor that significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it especially useful for the treatment of secondary glaucomas with an increased phagocytosis load but also for other open angle glaucomas.
ARTICLE | doi:10.20944/preprints202305.1629.v1
Subject: Engineering, Aerospace Engineering Keywords: Earth’s near space; Biological Samples Exposure; Mars; Venus; atmosphere; astrobiology
Online: 23 May 2023 (08:47:39 CEST)
Earth’s near space is a region between 20 and 100 km above sea level, which is characterized by low temperature, low atmospheric pressure, harsh radiation, and extreme dryness. These conditions are analogous to the surface of Mars and the atmosphere of Venus, and thus make it a unique natural lab for astrobiologists. To address the important astrobiological questions of the effects of the near space environmental conditions on biology and of the survival strategies of representative organisms in this planetary analog, teams from the Chinese Academy of Sciences have developed a scientific balloon platform named the Chinese Academy of Sciences Balloon-Borne Astrobiology Platform (CAS-BAP) and carried out a series of experiments in lower near space since 2019. Here, we describe the Biological Samples Exposure Payload (BIOSEP) loaded on CAS-BAP with respect to its structure and function. The primary role of BIOSEP is to expose biological/chemical samples to the planetary analog environments of Earth’s lower near space. Exposed samples will be returned to laboratories for morphological, physiological, chemical, and genetic analyses. The development of BIOSEP and associated biological exposure experiments will improve our understanding of the livelihood of potential Mars lives and the potential habitability of the atmosphere regions of other planets in the Solar System and beyond.
ARTICLE | doi:10.20944/preprints201811.0600.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: angle closure model; glaucoma; trabecular meshwork; outflow facility
Online: 27 November 2018 (08:42:09 CET)
Purpose: To investigate the extent of anterior chamber angle circumference needed to maintain a physiological outflow facility (C). Methods: Twenty anterior segments of porcine eyes were assigned to 5 groups, each with a different degree of cyanoacrylate-mediated angle closure: 90° (n = 4), 180° (n = 4), 270° (n = 4), 360° (n = 4) and four unoccluded control eyes. The outflow facility was measured at baseline, 3, 12, 24, and 36 hours after angle closure. Outflow patterns were evaluated with canalograms and the histomorphology was compared. Results: Baseline outflow facilities of the five groups were similar (F = 0.922, P = 0.477). Complete, circumferential occlusion over 360° induced a significant decrease in facility from baseline at all time-points (P ≤ 0.023 at 3, 12, 24 and 36 hours). However, no difference from baseline was found in any of the partially-occluded (0–270°) groups (F ≥ 0.067, P ≥ 0.296 at 3, 12, 24 and 36 hours). The canalograms confirmed the extent of occlusion with flow through the unblocked regions. Histology revealed no adverse effects of blockage on the TM or aqueous plexus in the unoccluded angle portions. The unoccluded TM appeared normal. Conclusion: Cyanoacrylate-mediated angle occlusion created a reproducible angle closure model. 90° of unoccluded anterior chamber angle circumference was sufficient to maintain physiological outflow. This model may help understand how outflow can be regulated in healthy, nonglaucomatous TM.
ARTICLE | doi:10.20944/preprints201804.0007.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: pigment dispersion syndrome; pigmentary glaucoma; trabecular meshwork; phagocytosis; migration; contraction; cytoskeleton; gene microarray; Rho signaling pathway
Online: 2 April 2018 (07:00:45 CEST)
Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.
ARTICLE | doi:10.20944/preprints201802.0028.v2
Subject: Medicine And Pharmacology, Ophthalmology Keywords: ab interno trabeculectomy; intraocular pressure; outflow facility; canalogram; trabecular meshwork
Online: 27 March 2018 (05:13:49 CEST)
Purpose: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods: In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µL/min and 10 µL/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. Results: At 5 µL/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µL/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µL/min (first ablation: 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation: 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.
ARTICLE | doi:10.20944/preprints202012.0354.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: meprin α; meprin β; zinc metalloproteinase; uHTS
Online: 14 December 2020 (16:36:57 CET)
Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in pre-clinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultra-high throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified 5 selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These are the most selective inhibitors of meprin α to date.
ARTICLE | doi:10.20944/preprints201806.0075.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: glaucoma; nitric oxide; spectral domain optical coherence tomography; aqueous humor outflow tract; physiology
Online: 6 June 2018 (06:09:24 CEST)
Purpose: To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO). Methods: In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 µM DETA-NO) on outflow facility were compared to controls (n=8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 µM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macro script and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results: The facility increased after DETA-NO (0.189±0.081 μL/min·mmHg, p=0.034) and AIT (0.251±0.094 μL/min·mmHg, p=0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (0.190±0.074 μL/min·mmHg, p=0.023) and CSA by 13.9% (p<0.001). L-NAME + ET-1 decreased CSA by -8.6% (p<0.001). NO increased the diameter of focal constrictions 5.0±3.8 fold. Conclusions: NO can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.
ARTICLE | doi:10.20944/preprints202012.0383.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: meprin α; meprin β; zinc metalloproteinase; medicinal chemistry; probe development
Online: 15 December 2020 (12:56:31 CET)
Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.
ARTICLE | doi:10.20944/preprints201806.0436.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: pigmentary glaucoma; trabecular meshwork; Goniotome; intraocular pressure; outflow facility
Online: 27 June 2018 (09:30:53 CEST)
Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P<0.01). Outflow facility in G (0.38±0.07 µl/min/mmHg) was higher than C (0.16±0.02 µl/min/mmHg, P<0.01). After the second 90° TM excision, IOP in G (6.46±0.81 mmHg, n=7) was significantly lower than C (20.25±1.66 mmHg, n=8, P<0.001), while the outflow facility in G (0.50±0.05 µl/min/mmHg, n=7) was higher than C (0.16±0.01 µl/min/mmHg, n=8, P<0.001). Compared to the first excision, excision of an additional 90° did not change of IOP (P=0.20) or outflow facility (P=0.17) further. Conclusion: Excision of 90° of TM in a pigmentary glaucoma model using an aspirating dual-blade decreased IOP and increased outflow facility. Translational Relevance: Microsurgical TM excision over 90° can effectively restore outflow in pigmentary glaucoma.
ARTICLE | doi:10.20944/preprints202306.0029.v1
Subject: Environmental And Earth Sciences, Ecology Keywords: PLUS model; InVEST model; Land use; Habitat quality; Temperate desert subzone of Ordos Plateau
Online: 1 June 2023 (05:33:45 CEST)
Habitat quality has great significance for regional ecological conservation and human welfare. In this study, we evaluated the spatial and temporal characteristics of land use and habitat quality in the temperate desert sub-region of Ordos Plateau using patch-generating land use simulation (PLUS) and integrated valuation of ecosystem services and trade-offs (InVEST) models. From 2000 to 2020, the areas of grassland, cropland, and unused land in the study area increased significantly; the areas of water bodies and woodland increased slightly; and the area of wasteland decreased significantly. Moreover, the habitat quality in the temperate desert subzone of the Ordos Plateau showed a trend of increasing and then decreasing from 2000 to 2020. The areas of lower and low habitat quality first decreased and then increased, and the overall area decreased over time. Conversely, the areas of high and higher habitat quality initially increased and then decreased, and the overall area increased over time. The area of medium habitat quality first decreased and then increased, although the overall change was minimal. Based on the PLUS model, the habitat quality of the study area in 2025 predicted under the natural development scenario was compared with that predicted under the ecological conservation scenario, showing higher habitat quality and lower habitat degradation under the ecological conservation development scenario. These results can be used to provide a scientific basis and decision reference for the sustainable use of land resources and high-quality socio-economic development in the temperate desert sub-region of the Ordos Plateau.
ARTICLE | doi:10.20944/preprints202305.1806.v1
Subject: Chemistry And Materials Science, Paper, Wood And Textiles Keywords: phenol-formaldehyde resin; soybean meal; soy-based adhesives; curing; plywood
Online: 25 May 2023 (10:55:13 CEST)
To develop a lower-cost, excellent performance, and environmentally friendly phe-nol-formaldehyde (PF) resin, soybean meal was used to modify PF resin, and soybean meal-phenol-formaldehyde (SMPF) resins were prepared. Their physicochemical properties and curing performance were investigated, showing that SMPF resins have higher curing tempera-tures than PF resin. The Fourier transform infrared spectroscopy (FTIR) results indicated that the cross-linking reaction occurred between the amino groups of soybean protein and the hy-droxymethyl phenol. Moreover, with the addition of soybean meal, the viscosity of SMPF in-creased while the gel time decreased. It is worth mentioning that SMPF-2 resin has favorable viscosity, short gel time, low curing temperature (135.78 °C), and high water resistance and bonding strength (1.01 MPa). Finally, all the plywoods bonded with SMPF resins have good water resistance and bonding strength, which could meet the Standard (GB/T 17657-2013, type I) for plywood. The optimized SMPF resins showed the potential application to replace part of PF resin in the wood industry.
ARTICLE | doi:10.20944/preprints201804.0033.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: cordycepin; adenosine A1 receptor; prolactin; anti-obesity
Online: 3 April 2018 (07:53:24 CEST)
Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A1 receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.
ARTICLE | doi:10.20944/preprints201608.0030.v2
Subject: Social Sciences, Psychology Keywords: occupational stress; job burden-capital model; structural equation model; depression; well-being
Online: 4 August 2016 (12:47:57 CEST)
Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF=5.37, AGFI=0.915, NNFI=0.945, IFI=0.952, RMSEA=0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.