bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning Instructed Microfluidic Synthesis of Curcumin-loaded Liposomes
Authors: Francesco Valentina Di , Boso Daniela P. , Moore Thomas L. , Schrefler Bernhard A. , Decuzzi Paolo 
Published: June 2023

Abstract
The association of machine learning (ML) tools with the synthesis of nanoparticles has the potential to streamline the development of more efficient and effective nanomedicines. The continuous-flow synthesis of nanoparticles via microfluidics represents an ideal playground for ML tools, where multiple engineering parameters – flow rates and mixing configurations, type and concentrations of the reagents – contribute in a non-trivial fashion to determine the resultant morphological and pharmacological attributes of nanomedicines. Here we present the application of ML models towards the microfluidic-based synthesis of liposomes loaded with a model hydrophobic therapeutic agent, curcumin. After generating over 200 different liposome configurations by systematically modulating flow rates, lipid concentrations, organic:water mixing volume ratios, support-vector machine models and feed-forward artificial neural networks were trained to predict, respectively, the liposome dispersity/stability and size. This work presents an initial step towards the application and cultivation of ML models to instruct the microfluidic formulation of nanoparticles.
The long-term effects of the first and second glaucoma drainage implant surgery in patients with primary open-angle glaucoma
Authors: Morita Shuu , Hamanaka Teruhiko , Sakurai Tetsuro , Watanabe Satoshi , Sakanishi Yoshihito , Ishida Nobuo , Ebihara Nobuyuki 
Published: June 2023

Abstract
Background
To investigate the long-term outcome of non-valved glaucoma drainage implant surgery (GDIS) in primary open-angle glaucoma (POAG) patients divided in Group I (patients who underwent the first GDIS) and Group II (patients who underwent the second GDIS because of the failed first GDIS).
Methods
Intraocular pressure (IOP), visual acuity (VA), visual field defect (VFD), medication score (MS), survival rate, complications, and patient background was retrospectively analyzed. Two success criteria were set: Criteria 1) IOP reduction ≥ 20% and 5 < IOP ≤ 21, Criteria 2) IOP reduction ≥ 20% and 5 < IOP ≤ 14.
Results
There were 136 eyes of 109 patients in Group I and 32 eyes of 27 patients in Group II. In Group I and II, mean preoperative IOP was 26.7 ± 6.7 mmHg and 23.7 ± 3.5 mmHg, respectively (P = 0.09). No statistically significant difference in postoperative IOP reduction was found between the two groups (P = 0.39). At 5-years postoperative, the Criteria 1 (Criteria 2) survival rate in Group I and Group II was 60.4% (31.7%) and 61.2% (25.6%), respectively (Criteria 1: P = 0.24; Criteria 2: P = 0.48). No significant difference in VA, VFD change, MS, or complications was observed. Young patient age was the only significant factor for failure in Group Ⅰ (P = 0.03).
Conclusion
The second GDIS may be as effective as the first GDIS for IOP reduction in POAG patients, however, there is a high risk of failure in young-age patients and the surgery may be ineffective in eyes requiring Criteria 2.
Endoplasmic Reticulum Stress Aggravates Inflammatory Bowel Disease by Triggering TLR2 Signaling Pathway
Authors: Wu Weijie , Zhao Yan , Hu Tian , Long Yan , Zeng ya , Li Mengling , Peng Siyuan , Hu Jinyue , Shen Yueming 
Published: June 2023

Abstract
Background:
Endoplasmic reticulum stress (ERS) and Toll-like receptor 2 (TLR2) signaling play an important role in inflammatory bowel disease (IBD); however, the link between TLR2 and ERS in IBD is unclear. This study investigated whether ERS and TLR2 mutually regulate and have a pro-inflammatory role in IBD pathogenesis.
Methods:
The THP-1 cells were treated with TLR2 agonist (Pam3CSK4), ERS inducer (TG) or inhibitor (TUDCA). The expressions of TLR1-TLR10 were detected by qRT-PCR or Western blot analysis. The expressions of TNF-α, IL-1β, IFN-β and IL-8 were measured by qRT-PCR and ELISA. The IBD mouse model was established by TNBS in the modeling group. TUDCA was used in the treatment group. The degree of colitis was assessed by comparing histological scores and DAI scores in each group.The expressions of Grp78 and TLR2 in intestinal mucosa were detected by immunohistochemistry.
Results:
The ERS inducer (TG) can increase the expressions of TLR2 and TLR5 after inducing ERS in THP-1 cells, while this effect is inhibited by TUDCA. However, the TLR2 agonist (Pam3CSK4) has no significant effect on the expressions of GRP78 and CHOP proteins. Treatment of THP-1 cells by TG and Pam3CSK4 together can significantly promote the expression of TNF-α, IL-1β and IL-8. In vivo experiments, TUDCA can inhibit intestinal mucosal inflammation and the expressions of Grp78 and TLR2. Compared with normal controls, the protein expressions of GRP78 and TLR2 in the colon mucosa of CD patients were significantly elevated.
Conclusions:
ERS aggravates inflammatory reaction in IBD by activating the TLR2 signaling pathway, making it a potential therapeutic target for IBD.
Analysis of Effects of Risk Factors and Disease History on Cognitive Levels of Older Adults in Nursing Homes: A Cross-Sectional Study
Authors: Rekawati Etty , Eriska Winda , Rachmawati Utami , Wati Dwi Nurviyandari Kusuma , Sahar Junaiti , Andriyanto Arief , Wang Jing-Jy 
Published: June 2023

Abstract

Background
The increase in the older adult population has resulted in an epidemiological transition—namely, a shift in disease patterns from infections and nutritional disorders to degenerative diseases such as diabetes, hypertension, cancer, and coronary heart disease. Disorders due to other decreased functions that often occur in older adults are also related to cognitive function. The purpose of the study was to analyse the effects of risk factors and disease history on the cognitive level of older adults in nursing homes.
Methods
This research involved an analytical survey with a cross-sectional approach. The research subjects were 372 older adults living in nursing homes. The data in this study were obtained through interviews using demographic data questionnaires and the Montreal Cognitive Assessment (MoCA). Data analysis was performed using a chi-square test.
Results
The results showed that there was a relationship between risk factors and the cognitive levels of older adults, including gender (0.003), ethnicity (0.04), education level (0.001), memory complaints (0.001), history of smoking (0.03), alcohol consumption (0.001), fruit and vegetable consumption (0.04), and occupation (0.02). Furthermore, there was a relationship between disease history and the cognitive levels of the older adults with a p-value of 0.02 (< 0.05).
Conclusions
There was a relationship between several risk factors and disease history and the cognitive levels of the older adults. One effort that can be undertaken by nurses is to identify and control factors that can affect cognitive functioning in older adults.
The role and mechanism of quercetin via TLR4/MyD88/IRAK4 signaling pathway in the treatment of allergic rhinitis
Authors: Kang Chenglin , Liu Jiangqi , Wu Zhisheng , Li Xiaomei , Liu Peng , Liu Yue , Zeng Xianhai , Zhao Hailiang , Qiu Shuqi 
Published: June 2023

Abstract
An ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model was established to investigate whether quercetin (QUE) treats AR via TLR4/MyD88/IRAK4 signaling pathway. SPF grade Balb/c mice were randomly divided into 4 groups: normal control (NC), OVA, dexamethasone (DEX), and (QUE) groups. OVA and aluminum hydroxide [AL(OH)3] were injected intraperitoneally for basic sensitization and OVA was dripped into the nose for challenge to induce a mouse model of AR. The mice were scored by observing the behaviors of scratching, sneezing and runny nose to assess whether the modeling was successful. The treatment groups (DEX and QUE) were given the corresponding drugs for gavage treatment for 1 week after successful modeling, and the OVA and NC groups were treated with normal saline instead. The levels of OVA-IgE, IL-4, IL-13, IL-1β, IL-17 and IL-10 in serum were measured by enzyme-linked immunosorbent assay (ELISA); the changes of mice nasal mucosa were observed in hematoxylin-eosin (HE) stained histopathological sections; the relative expression levels of mRNA and protein of TLR4, MyD88, IRAK4, NF-κB in lung tissues were measured by quantitative real-time PCR (qPCR) and western blot, respectively; the changes in the percentages of regulatory T cells (Treg) and helper T cells 17 (Th17) in splenocytes were detected by flow cytometry. The results showed that the allergic symptoms scores were greater than 10 points and the expression levels of OVA-IgE, IL-4, IL-13, IL-1β and IL-17 in the serum increased and the expression level of IL-10 decreased in the OVA group compared with NC group. HE staining of the nasal cavity suggested detachment and necrosis of the nasal mucosa, tissue edema, and inflammatory cell infiltration in the OVA group. The relative expression levels of mRNA and protein of TLR4, MyD88, IRAK4, NF-κB in lung tissues were increased and the percentage of Treg cells decreased and the percentage of Th17 cells increased in splenocytes of the OVA group. Based on these results, we speculate that QUE may inhibit inflammatory responses and induce immune tolerance via TLR4/MyD88/IRAK4 signaling pathway in mice model of AR.
Neuronal protein kinase C epsilon–regulated endoplasmic reticulum stress and autophagic formation mediated neuropathic manifestation in diabetic neuropathy
Authors: Kan Yu-Yu , Chang Ying-Shuang , Liao Wen-Chieh , Chao Tzu-Ning , Hsieh Yu-Lin 
Published: June 2023

Abstract
In chronic diabetic neuropathy (DN), the cellular mechanisms of neuropathic manifestation remain unclear. Protein kinase C epsilon (PKCε) is an intracellular signaling molecule that mediates chronic pain. This paper addresses the DN-associated chronic neuropathic manifestations linked to long-term upregulated PKCε–mediated endoplasmic reticulum (ER) stress and autophagic formation. We found that the course of thermal hyperalgesia and mechanical allodyniawas associated with PKCε upregulation after DN, but not skin denervation. Pathologically, PKCε upregulation was associated with the expression of inositol-requiring enzyme 1α (IRE1α; ER stress–related molecule) and ubiquitin D (UBD), which are involved in the ubiquitin-proteasome system (UPS)-mediated degradation of misfolded proteins under ER stress. Manders coefficient analyses revealed an approximately 50% colocalized ratio for IRE1α(+):PKCε(+) neurons (0.34–0.48 for M1 and 0.40–0.58 for M2 Manders coefficients). The colocalized coefficients of UBD/PKCε increased (M1: 0.33 ± 0.03 vs. 0.77 ± 0.04, p < 0.001; M2: 0.29 ± 0.05 vs. 0.78 ± 0.04; p < 0.001) in the acute DN stage. In addition, the regulatory subunit p85 of phosphoinositide 3-kinase, which is involved in regulating insulin signaling, exhibited similar expression patterns to those of IRE1α and UBD; for example, it had highly colocalized ratios to PKCε. Upregulated PKCε–mediated neuropathic manifestation as well as ER stress and UPS-related molecule upregulation was reversed by PKCεv1-2, a PKCε specific inhibitor. The ultrastructural examination further confirmed that autophagic formation was associated functional PKCε. Collectively, this finding confirmed the pivotal roles of PKCε in DN-associated neuropathic manifestation and neuropathology.
Dynamic modeling of thin-walled CFRP surface milling and the effect of chatter on surface quality
Authors: Wang Fuji , Deng Jun , Fu Rao , Lin Yongquan , He Qingsong , Ma Xing 
Published: June 2023

Abstract

Milling a thin-walled curved structure is prone to chattering, and the quality of the machined surface cannot be guaranteed. For carbon fiber reinforced plastic (CFRP) parts with a strong anisotropic characteristic, the tool will contact different fiber directions, resulting in a large change in dynamic cutting force and more complex chatter. Thus, this study introduced the anisotropic and laminated characteristics of CFRP into the machining dynamic model and stability domain solution prediction in milling CFRP. Meanwhile, a dynamic cutting force model under the regenerating mechanism was first proposed by considering the instantaneous fiber cutting angle and the cutting edge length of the instantaneous contact micro-element with the same fiber layer. Moreover, the dynamic model for milling this CFRP workpiece was established based on the dynamic cutting force model and dynamic characteristics of the workpiece. The stability lobe diagram was drawn, and the stable cutting regions for milling CFRP were obtained. Also, experimental verifications were conducted, and the chattering and stable machining conditions were well predicted. Compared with the stable region obtained without considering the anisotropic characteristic of CFRP, the predicted maximum peak value of the stable region increased by 49.7%, proving the accuracy of the proposed method.
Submerged wall jet on a macro-rough boundary: turbulent flow characteristics and their scaling laws
Authors: Chowdhury Sammelan , Sen Dhrubajyoti , Dey Subhasish 
Published: June 2023

Abstract
This study presents the turbulence characteristics and the scaling laws in a horizontal submerged wall jet on an array of hemispherical macro-rough elements forming an open-channel boundary. The flow field was measured by an acoustic Doppler system, called Vectrino. The turbulence characteristics on a macro-rough boundary, being different from those on smooth boundary, are discussed from the perspective of decay of the local-peak parameters, similarity, and growth of the length scales. The vector plots, streamwise velocity flow field, and the jet velocity variations show that the decay rate of jet velocity in a submerged jet on a macro-rough boundary is initially sharp and then gradually drops down to become independent of streamwise distance. The growth rate of the jet boundary layer thickness is initially slow and then becomes fast as it tends to reach the free surface. On the other hand, the plots of the Reynolds shear stress and turbulence intensities, and the variations of their local-peak magnitudes reveal the gradual damping of these parameters with the streamwise distance. These results encapsulate the recovery of a submerged jet on a macro-rough boundary to become an open channel flow. The most important outcome is that the streamwise velocity, Reynolds shear stress, and turbulence intensities in the fully developed zone are found to be self-similar when the velocity is scaled with the local-peak velocity against jet half-width, and the Reynolds shear stress and turbulence intensities are scaled with their respective local-peak magnitudes against half-width of Reynolds shear stress. The boundary shear stress diminishes with an increase in streamwise distance.
Physiological and metabolomic analyses provide insights into the cadmium tolerance of Sophora tonkinensis
Authors: Chen Hao , Huang Su-Hua , Tang Dan-Feng , Liang Ying , Qin Shuang-Shuang , Quan Chang-qian , Wei Gui-Li , Wei Kun-Hua , Wei Fan 
Published: June 2023

Abstract
Sophora tonkinensis is an important medicinal plant native to China and Vietnam, growing in stony mountains and calcareous or sandstone hill slopes. Cadmium negatively affects the quality of S. tonkinensis, indirectly threatening human health. To elucidate the physiological and metabolic mechanism of S. tonkinensis in response to Cd stress, we conducted a hydroponic greenhouse experiment and measured the growth parameters of S. tonkinensis treated with 0, 20, 40, 60, and 80 µmol L− 1 Cd. Furthermore, metabolite changes in S. tonkinensis roots were investigated using liquid chromatography–tandem mass spectrometry. We identified 380 differential metabolites, and significant differences were detected in the varieties and quantities of amino acids, organic acids, fatty acids, and ketones, which have significant impact on S. tonkinensis stress response to Cd, under different Cd concentrations. S. tonkinensis resisted the stress induced by 40 µmol L− 1 Cd by upregulating lysine, arginine, histidine, glycine, sarcosine, tryptophan, D-proline, DL-serine, cellobiose, linoleic, indole, cytosine, and genistein contents and downregulating betaine, leucine, citrate, oleic, trehalose, and daidzein contents. Linoleic, palmitic, citrate, maackiain, isomaltose, and cinnavalininate contents were upregulated, and L-phenylalanine, sarcosine, indole acetate, and cytosine were downregulated in response to 80 µmol L− 1 Cd stress. KEGG pathway enrichment analysis showed that the isoflavonoid biosynthesis pathway was significantly enriched, indicating its important role in the Cd resistance of S. tonkinensis. This study provides important information for understanding the tolerance and accumulation mechanisms of S. tonkinensis in response to Cd stress, which will contribute to the breeding of medicinal plant.
Clinical data, survival, and prognosis of 426 cases of oropharyngeal cancer: A retrospective analysis
Authors: Li Jiancheng , Zhuo Feng , Wang Xuji , Guo Yun , Jiang Lina 
Published: June 2023

Abstract
Objective: To determine factors influencing survival and prognosis of HPV-related and non-related oropharyngeal cancer.
Methods: Subjects were determined from the three hospitals in Anhui province of China between 2015 and 2020. Paraffin-embedded specimens from participants’ tissues were analyzed, and the subjects were classified as P16+ and P16– cases using immunohistochemical staining for P16 protein.
Results: 426 patients with oropharyngeal cancer were recruited in this study, 108 cases were found to be P16+. The subjects were treated with the three regimens: surgery/radiotherapy/chemotherapy (SRCT), radiotherapy/chemotherapy (RCT), surgery/chemotherapy (SCT). There were no statistically significant differences in the survival rates within the P16+ or P16– groups between the three treatment regimens (P > 0.05). The 1-, 3-, and 5-year survival rates for P16+ and P16– groups were statistically different (P < 0.05). Multivariate analysis showed that age, physical health status, smoking, and alcohol abuse were independent risk factors affecting the prognosis of P16+ cases, while pathological grading and TNM staging were independent risk factors affecting the P16– cases.
Conclusion: The etiology, pathogenesis, survival status, and prognostic factors of HPV-related oropharyngeal cancer are very different from those of traditional oropharyngeal cancer. Thus, HPV-related oropharyngeal cancer could be classified as a separate type of disease. This distinction could be of great significance for treatment, prevention, and prognostication of oropharyngeal cancer.
Non-alcoholic Fatty Liver Disease as risk factors for Chronic Kidney Disease: A Bidirectional Mendelian Randomization Study
Authors: Chen Maohua , Nian Qichun , Zheng Xinlei 
Published: June 2023

AbstractBackground Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are two significant global public health concerns. Recent reports suggest that NAFLD may increase the risk of developing CKD. However, the specific causal relationship between these two conditions has not been thoroughly investigated. Methods In this study, we analyzed genome-wide association study (GWAS) summary data of CKD and NAFLD. We identified single nucleotide polymorphisms (SNPs) associated with these diseases as instrumental variables (IVs) at a genome-wide significance level (P < 1.0 × 10− 5) at first. Then, for Mendelian randomization (MR) analysis, we primarily used the inverse variance weighted (IVW) method, while employing the MR-Egger, weighted model, simple model, and weighted median methods for quality control. We also conducted sensitivity analysis to ensure the robustness of the results. Results Our MR analysis revealed a significant association between genetically predicted NAFLD and an increased risk of CKD using the IVW method (OR, 0.94; 95% CI, 0.89–1.00;P = 0.049). However, we found no evidence to support a causal relationship between CKD on NAFLD (IVW:P = 0.467). Conclusion Based on our findings, there is a causal relationship between NAFLD and CKD. Further investigations are necessary to elucidate the impact of these two diseases, as our results do not support a causal effect of CKD on NAFLD.
Fe-dope Nickel Selenide @Tri-Nickel Diselenide heterostructure with efficient and stable water splitting for hydrogen production
Authors: Luo ZhongKe , Tong LongZhi , Lin Zhiping , Amin R. S. , Ren Junna , El-Khatib K. M. , Wang Chao 
Published: June 2023

Abstract
To meet the increasing demand for clean energy, environmentally friendly and efficient transition metal selenides (TMSes) electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are being developed. There is an urgent need for a rational design of bifunctional non-precious metal catalysts with advanced structure and superior composition. In water splitting for the production of clean hydrogen energy, transition metal selenides have promising applications. We prepared a catalyst by a two-step hydrothermal method, the crystal structure of the catalysts can be easily adjusted by adjusting the concentration of the selenizing agent, when the concentration of the selenizing agent is 0.6 mmol, a phase transition occurred, and forming NiSe@Ni3Se2 heterostructure, reaching a current density of 10 mA cm−2 at an overpotential of 214 mV with a low Tafel slope of 41 mV dec−1. When the concentration of selenide was increased to 0.6 mmol, the prepared FNS/0.6 demonstrated excellent HER performance. At 10 mA cm-2 current density, the overpotential was only 156 mV. Moreover, the monolithic hydrolysis electrolyzer assembled with FNS/0.6 as the anode and cathode electrodes showed a low cell voltage of 1.7 V at a current density of 10 mA cm-2, and almost no attenuation was observed after a 72 h stability test. The excellent electrocatalytic performance of the prepared catalysts was attributed to the formation of nickel-selenide heterostructures and the synergistic effect of two-dimensional Fe-doped MOF, which provide abundant active sites. This study provides a good idea for the development of high activity and high stability catalysts.