bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia-induced Wnt/β-catenin signaling activation in subchondral bone osteoblasts leads to an osteoarthritis-like phenotype of chondrocytes in articular cartilage
Authors: Li Fang , Tan Qizhao , Li Feng , Zhang Ke , Liu Zhongjun , Tian Yun , Zhu Tengjiao 
Published: April 2023

Background: Osteoarthritis (OA) is a whole-joint disease and characterized by alterations in the articular cartilage, subchondral bone, ligaments, and synovial membrane. The crosstalk between cartilage and subchondral bone plays a crucial role in the pathogenesis and progression of OA. Hypoxia has been reported to play an important role in cartilage degradation and subchondral bone remodeling in OA. In this study, we aimed to identify the involvement of hypoxia in modifying the osteoblast phenotypes and determine whether these alterations could influence the metabolism of chondrocytes.Methods: First, the levels of Hif-1α in subchondral bone of different compartments in patients with OA were assessed using immunohistochemistry (IHC). In in vitro, human primary osteoblasts were cultured under hypoxic and normoxic conditions, and the hypoxic or normoxic conditioned media (HCM and NCM) were used to culture human primary chondrocytes. Then, phenotypic changes in osteoblasts were assessed using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the expression of type II collagen (COL2A1), aggrecan (ACAN), SRY-related high-mobility group-box gene 9 (SOX9), matrix metalloproteinase 13 (MMP13), and matrix metalloproteinase 3 (MMP3) in chondrocytes was measured using RT-PCR. Finally, the serum levels of Wnt-related proteins were determined using ELISA.Results: Hif-1α was significantly increased in severely sclerotic subchondral bone compared to less damaged subchondral bone. β-Catenin and SOST were identified as upregulated and downregulated in hypoxic osteoblasts, respectively. The hypoxia-induced results were confirmed by ELISA. Stimulating human primary chondrocytes with HCM significantly induced MMP13 and MMP3 and inhibited COL2A1, ACAN, and SOX9 mRNA expression. The serum levels of DKK-1 were significantly increased in human OA.Conclusion: Together, these findings revealed that hypoxia in subchondral bone is a key factor in the crosstalk between chondrocytes and osteoblasts and facilitates the shift of chondrocytes toward an OA-like phenotype probably by activating the Wnt/β-catenin signaling pathway in osteoblasts.
Isolating the speed factor is crucial in gait analysis for Parkinson’s disease
Authors: Patoz Aurélien , Malatesta Davide , Burtscher Johannes 
Published: April 2023

IntroductionParkinson’s disease (PD) is characterized by an alteration of the walking gait, frequently including a slower self-selected walking speed (SSWS). Although the reduction of walking speed is inherent to people with PD, such speed reduction also represents a potential confounding factor that might partly explain the observed gait differences between PD and control participants.MethodsIn this study, each participant walked along a 25 m level corridor during which vertical ground reaction force signals were recorded using shoes equipped with eight pressure sensors. Vertical ground reaction force signals (using statistical parametric mapping) and temporal and kinetic variables as well as their related variability and asymmetry (using Student’s t-test) were compared between PD (n = 54) and walking-speed-matched control subjects (n = 39).ResultsStatistical parametric mapping did not yield significant differences between PD and control groups for the vertical ground reaction force signal along the walking stance phase. Stride time and single support time (equivalent to swing time) were shorter and peak vertical ground reaction force was larger in PD patients compared to controls (p ≤ 0.05). However, the single support time was no longer different between people with PD and healthy subjects when expressed relatively to stride time (p = 0.07). While single support, double support, and stance times were significantly more variable and asymmetric for PD than for the control group (p ≤ 0.05), stride time was similar (p ≥ 0.07).DiscussionThese results indicate that at matched SSWS, PD patients adopt a higher cadence than control participants. Moreover, the temporal subdivision of the walking gait of people with PD is similar to healthy individuals but the coordination during the double support phase is different. Hence, this study indicates that isolating the speed factor is crucial in gait analysis for PD.
Calcium-binding properties, stability, and osteogenic ability of phosphorylated soy peptide-calcium chelate
Authors: Kong Xiao , Xiao Ziqun , Chen Yuhang , Du MengDi , Zhang Zihui , Wang Zhenhua , Xu Bo , Cheng Yongqiang , Yu Tianying , Gan Jing 
Published: April 2023

IntroductionBioactive peptides based on foodstuffs are of particular interest as carriers for calcium delivery due to their safety and high activity. The phosphorylated peptide has been shown to enhance calcium absorption and bone formation.MethodA novel complex of peptide phosphorylation modification derived from soybean protein was introduced, and the mechanism, stability, and osteogenic differentiation bioactivity of the peptide with or without calcium were studied.ResultThe calcium-binding capacity of phosphorylated soy peptide (SPP) reached 50.24 ± 0.20 mg/g. The result of computer stimulation and vibration spectrum showed that SPP could chelate with calcium by the phosphoric acid group, carboxyl oxygen of C-terminal Glu, Asp, and Arg, and phosphoric acid group of Ser on the SPP at a stoichiometric ratio of 1:1, resulting in the formation of the complex of ligand and peptide. Thermal stability showed that chelation enhanced peptide stability compared with SPP alone. Additionally, in vitro results showed that SPP-Ca could facilitate osteogenic proliferation and differentiation ability.DiscussionSPP may function as a promising alternative to current therapeutic agents for bone loss.
Potential therapeutic benefits of unconventional oils: assessment of the potential in vitro biological properties of some Rubiaceae, Cucurbitaceae, and Brassicaceae seed oils
Authors: Fratianni Florinda , Amato Giuseppe , De Feo Vincenzo , d'Acierno Antonio , Coppola Raffaele , Nazzaro Filomena 
Published: April 2023

IntroductionSeed oils are versatile in the food sector and for pharmaceutical purposes. In recent years, their biological properties aroused the interest of the scientific world.Materials and methodsWe studied the composition of fatty acids (FAs) and some in vitro potential therapeutic benefits of five cold-pressed commercial oils obtained from broccoli, coffee, green coffee, pumpkin, and watermelon seeds. In particular, we assayed the antioxidant activity (using diphenyl-1-picrylhydrazyl (DPPH) and azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays). In addition, through the fatty acid composition, we calculated the atherogenicity index (AI) and thrombogenicity index (TI) to evaluate the potential impact of such oils on cardiovascular diseases. Furthermore, we assessed the in vitro anti-inflammatory capacity of the oils (evaluated through their effectiveness in preventing protein degradation, using bovine serum albumin as protein standard) and the ability of the oils to inhibit in vitro activity of three among the essential enzymes, cholinesterases and tyrosinase, involved in the Alzheimer's and Parkinson's neurodegenerative diseases. Finally, we evaluated the capacity of the oils to inhibit the biofilm of some pathogenic bacteria.ResultsThe unsaturated fatty acids greatly predominated in broccoli seed oil (84.3%), with erucic acid as the main constituent (33.1%). Other unsaturated fatty acids were linolenic (20.6%) and linoleic (16.1%) acids. The saturated fatty acids fraction comprised the palmitic (6.8%) and stearic acids (0.2%). Broccoli seed oil showed the best AI (0.080) and TI (0.16) indexes. The oils expressed a good antioxidant ability. Except for the watermelon seed oil, the oils exhibited a generally good in vitro anti-inflammatory activity, with IC50 values not exceeding 8.73 micrograms. Broccoli seed oil and green coffee seed oil showed the best acetylcholinesterase inhibitory activity; coffee seed oil and broccoli seed oil were the most effective in inhibiting butyrylcholinesterase (IC50 = 15.7 μg and 20.7 μg, respectively). Pumpkin and green coffee seed oil showed the best inhibitory activity against tyrosinase (IC50 = 2 μg and 2.77 μg, respectively). In several cases, the seed oils inhibited the biofilm formation and the mature biofilm of some gram-positive and gram-negative bacteria, with Staphylococcus aureus resulting in the most sensitive strain. Such activity seemed related only in some cases to the capacity of the oils to act on the sessile bacterial cells' metabolism, as indicated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method.
The short-term efficacy and safety of induction chemotherapy combined with PD-1 inhibitor or anti-EGFR in locoregionally advanced nasopharyngeal carcinoma
Authors: Xiang Xiaoyong , Chen Peng , Lan Fengming , Ma Li , Jin Jing , Zhang Ye 
Published: April 2023

PurposeThis study aimed to investigate the short-term efficacy and safety of induction chemotherapy (IC) combined with PD-1 inhibitor or anti-EGFR in the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC).Methods and materialsWe retrospectively reviewed the clinical data of 206 patients with LA-NPC, including IC combined with anti-PD-1 (57 patients), IC combined with anti-EGFR (28 patients), and IC alone (121 patients). The short-term efficacy was assessed at the end of IC and one month after overall treatment. According to the RECIST v1.1, the short-term efficacy of cervical lymph nodes and primary nasopharynx foci was divided into complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD). The overall response (ORR) was defined as the sum of CR and PR. Acute toxicities were graded according to the CTCAE v5.0. One-way analysis of variance (ANOVA) was used to compare differences in the numerical variables among groups. Fisher Freeman-Halton test or Pearson Chi-square test was used to compare classified variables.ResultsThe ORR rates of primary nasopharynx foci in IC, anti-EGFR, and anti-PD-1 group were 68.60%, 67.9%, and 94.7%, respectively, and the corresponding rates of ORR in cervical lymph nodes were 78.5%, 71.4%, and 93.0%, respectively. There was a statistical difference in the ORR between the three groups. Further analysis showed that after IC or overall treatment, the CR rate of primary nasopharynx foci in the anti-PD-1 group was significantly higher than the other two groups. The most common adverse effects were hematotoxicity, gastrointestinal toxicity, and transaminase elevation. However, there were no statistical differences in the frequency of any common adverse effects between the three groups.ConclusionsThe addition of anti-PD-1 based on IC significantly improved the short-term efficacy of LA-NPC and toxicities were tolerable.
The effect of triple reuptake inhibitor toludesvenlafaxine on neurological function in cerebral ischemic rats
Authors: Sun Xiaohui , Wang Tian , Zhou Lin , Zhang Ce , Fu Fenghua 
Published: April 2023

Purpose: The aim is to investigate the effect of toludesvenlafaxine (Tdv), a reuptake inhibitor of serotonin, norepinephrine, and dopamine, on the neurological function in cerebral ischemic rats and the underlying mechanisms.Material and Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) model was induced in rats and the neuroprotective effects of Tdv were evaluated by infarct size, Garcia test, and beam walking test. Neuronal apoptosis in the peri-infarct area was observed by TUNEL staining. And the apoptosis-related proteins were evaluated with Western blotting. The role of CREB pathway in effect of Tdv was also investigated using Western blotting and immunofluorescence.Results: In the MCAO/R model, administration of Tdv reduced the infarct size, promoted neural functional recovery, decreased the expression of Bax and Caspase-3, and increased the expression of Bcl-2 and BDNF. In addition, Tdv reduced neuronal apoptosis in the peri-infarct area. Tdv increased the expression of phosphorylated CREB. The application of the specific CREB inhibitor, compound 666-15, could reverse the anti-ischemic cerebral injury of Tdv in MCAO/R rats.Conclusion: Tdv ameliorated cerebral ischemic injury through reducing neuronal apoptosis and increasing the expression of BDNF via the activation of CREB pathway.
Efficacy and safety of apatinib versus sorafenib/placebo in first-line treatment for intermediate and advanced primary liver cancer: A systematic review and meta-analysis
Authors: Peng Dan , Cai Yongqing , Chen Geng , Hou Min , Luo Xiaofeng , Dongzhi Zhuoma , Xie Hongjun , Liu Yao 
Published: April 2023

Background: Apatinib is a novel tyrosine kinase inhibitor used in the treatment of advanced hepatocellular carcinoma (HCC). For decades, sorafenib has been a classic first-line treatment option for patients with HCC. This meta-analysis aimed to assess the efficacy and safety of apatinib versus sorafenib/placebo as first-line treatment for intermediate and advanced primary liver cancer (PLC).Methods: A literature search was performed via PubMed, Web of Science, CENTRAL, Embase, CNKI, VIP, and CBM. Data extraction from databases of other languages is not restricted. The Cochrane risk of bias tool, modified Jadad scale, Newcastle–Ottawa scale (NOS), and non-randomized studies of interventions (ROBINS-I) tool were employed to evaluate methodological qualities in original studies. Influence analysis was applied to assess the reliability of pooled results. Publication bias was evaluated using the funnel plot with Begg’s test and Egger’s test.Results: Seven studies were included in the systematic review and meta-analysis. Four randomized controlled trials (RCTs) and one clinical controlled trial (CCT) were used for comparing apatinib with placebo, and two retrospective clinical studies (RCSs) were used for comparing apatinib with sorafenib. Apatinib led to higher overall effects in objective response rate (ORR), disease control rate (DCR), and mean survival time (MST) over placebo (RR = 2.03, 95% CI = 1.46–2.81, p &lt; 0.0001, I2 = 0%; RR = 1.17, 95% CI = 1.04–1.33, p = 0.009, I2 = 45.8%; SMD = 2.63; 95% CI = 1.47–3.78, p &lt; 0.0001, I2 = 92.7%, respectively). Compared to sorafenib, apatinib showed no superiority in ORR and DCR but was inferior in the 6-month and 1-year survival rate (RR = 1.99, 95% CI = 0.85–4.65, p = 0.111, I2 = 68.3%; RR = 1.04, 95% CI = 0.73–1.47, p = 0.840, I2 = 0.0%; RR = 0.63, 95% CI = 0.42–0.97, p = 0.036, I2 = 0.0%; RR = 0.47, 95% CI = 0.29–0.79, p &lt; 0.0001, I2 = 0.0%, respectively). Apatinib had similar adverse effects over placebo but possessed a greater incidence rate of proteinuria and hypertension over sorafenib.Conclusion: In the first-line setting, apatinib might be an alternative treatment approach for patients with intermediate and advanced PLC. Sorafenib alone showed a better survival rate within 1 year and a lower incidence rate in hypertension and proteinuria than apatinib monotherapy.
Biological evaluation and in silico studies of novel compounds as potent TAAR1 agonists that could be used in schizophrenia treatment
Authors: Wang Yunjie , Liu Zhaofeng , Lu Jing , Wang Wenyan , Wang Lin , Yang Yifei , Wang Hongbo , Ye Liang , Zhang Jianzhao , Tian Jingwei 
Published: April 2023

Introduction: Schizophrenia is a serious mental illness that requires effective treatment with minimal adverse effects. As preclinical and clinical research progresses, trace amine-associated receptor 1 (TAAR1) is becoming a potential new target for the treatment of schizophrenia.Methods: We used molecular docking and molecular dynamics (MD) simulations to discover TAAR1 agonists. The agonistic or inhibitory effects of compounds on TAAR1, 5-HT1A, 5-HT2A, and dopamine D2-like receptors were determined. We used an MK801-induced schizophrenia-like behavior model to assess the potential antipsychotic effects of compounds. We also performed a catalepsy assay to detect the adverse effects. To evaluate the druggability of the compounds, we conducted evaluations of permeability and transporter substrates, liver microsomal stability in vitro, human ether-à-go-go-related gene (hERG), pharmacokinetics, and tissue distribution.Results: We discovered two TAAR1 agonists: compounds 50A and 50B. The latter had high TAAR1 agonistic activity but no agonistic effect on dopamine D2-like receptors and demonstrated superior inhibition of MK801-induced schizophrenia-like behavior in mice. Interestingly, 50B had favorable druggability and the ability to penetrate the blood-brain barrier (BBB) without causing extrapyramidal symptoms (EPS), such as catalepsy in mice.Conclusion: These results demonstrate the potential beneficial role of TAAR1 agonists in the treatment of schizophrenia. The discovery of a structurally novel TAAR1 agonist (50B) may provide valuable assistance in the development of new treatments for schizophrenia.
Evaluating the risk of knee osteoarthritis following unilateral ACL reconstruction based on an EMG-assisted method
Authors: Long Ting , Fernandez Justin , Liu Hui , Li Hanjun 
Published: April 2023

Objective: Anterior cruciate ligament reconstruction (ACLR) cannot decrease the risk of knee osteoarthritis after anterior cruciate ligament rupture, and tibial contact force is associated with the development of knee osteoarthritis. The purpose of this study was to compare the difference in bilateral tibial contact force for patients with unilateral ACLR during walking and jogging based on an EMG-assisted method in order to evaluate the risk of knee osteoarthritis following unilateral ACLR.Methods: Seven unilateral ACLR patients participated in experiments. The 14-camera motion capture system, 3-Dimension force plate, and wireless EMG test system were used to collect the participants’ kinematics, kinetics, and EMG data during walking and jogging. A personalized neuromusculoskeletal model was established by combining scaling and calibration optimization. The inverse kinematics and inverse dynamics algorithms were used to calculate the joint angle and joint net moment. The EMG-assisted model was used to calculate the muscle force. On this basis, the contact force of the knee joint was analyzed, and the tibial contact force was obtained. The paired sample t-test was used to analyze the difference between the participants’ healthy and surgical sides of the participants.Results: During jogging, the peak tibial compression force on the healthy side was higher than on the surgical side (p = 0.039). At the peak moment of tibial compression force, the muscle force of the rectus femoris (p = 0.035) and vastus medialis (p = 0.036) on the healthy side was significantly higher than that on the surgical side; the knee flexion (p = 0.042) and ankle dorsiflexion (p = 0.046) angle on the healthy side was higher than that on the surgical side. There was no significant difference in the first (p = 0.122) and second (p = 0.445) peak tibial compression forces during walking between the healthy and surgical sides.Conclusion: Patients with unilateral ACLR showed smaller tibial compression force on the surgical side than on the healthy side during jogging. The main reason for this may be the insufficient exertion of the rectus femoris and vastus medialis.
Effects of cadmium exposure during the breeding period on development and reproductive functions in rare minnow (Gobiocypris rarus)
Authors: Su Liangxia , Li Huanhuan , Qiu Ning , Wu Yinrui , Hu Bing , Wang Rui , Liu Jun , Wang Jianwei 
Published: April 2023

Cadmium is a common reproductive toxin in aquatic systems. Cd exposure of fish species at high concentrations can severely affect the reproductive function of fish. However, the underlying toxicity of cadmium exposure at low concentrations on the reproductive function in parental fish remains unclear. To investigate the impacts of cadmium exposure on reproductive capability, eighty-one male and eighty-one female rare minnows (Gobiocypris rarus) were exposed to cadmium at 0 (control group), 5 and 10 μg/L for 28 days, and then transferred into clean water to pair spawn. The results showed that cadmium exposure at 5 or 10 μg/L for 28 days in rare minnows could reduce the success rates of pair spawning in parent rare minnows, lessen no-spawning activities, and prolong the time for first spawning. Furthermore, the mean egg production of the cadmium exposure group increased. The fertility rate of the control group was significantly higher than that of the 5 μg/L cadmium exposure group. Anatomical and histological data further revealed that the intensity of atretic vitellogenic follicles significantly increased and spermatozoa vacuolated after cadmium exposure (p&lt; 0.05), but slightly increased the condition factor (CF), and relatively stable gonadosomatic index (GSI) values were also observed in the cadmium exposure groups. These observed results indicated that cadmium exposure at 5 or 10 μg/L affected the reproductive activity of paired rare minnow by accumulating Cd in the gonads, and the effect diminished over time. The reproductive risk of low-dose cadmium exposure to fish species remains a cause for concern.
Root architecture and visualization model of cotton group with different planting spacing under local irrigation
Authors: Gao Chao , Li Mingsi , Li Dongwei 
Published: April 2023

Planting spacing plays a key role in the root system architecture of the cotton group under local irrigation. This study used the Cellular Automata (CA) theory to establish a root visualization model for the cotton group at two different planting spacing (30 and 15 cm) within a leaching-pond. At a planting spacing of 30 cm, the lateral roots grew almost horizontally toward the irrigation point, and a logarithmic relationship was observed between root length density and soil water suction. However, at a planting spacing of 15 cm, the lateral roots exhibited overlapping growth and mainly competed for resources, and a power function relationship was observed between root length density and soil water suction. The main parameters of the visualization model for each treatment were essentially consistent with the experimental observations, with respective simulation errors were 6.03 and 15.04%. The findings suggest that the correlation between root length density and soil water suction in the cotton plants is a crucial driving force for the model, leading to a more accurate replication of the root structure development pathway. In conclusion, the root system exhibits a certain degree of self-similarity, which extends into the soil.