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Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and the expression and function of an uncharacterized protein RNF214 in HCC are still unknown. Phase separation has recently been observed to participate in the progression of HCC. In this study, we investigated the expression, function, and phase separation of RNF214 in HCC. We found that RNF214 was highly expressed in HCC and associated with poor prognosis. RNF214 functioned as an oncogene to promote the proliferation, migration, and metastasis of HCC. Mechanically, RNF214 underwent phase separation, and the coiled-coil (CC) domain of RNF214 mediated its phase separation. Furthermore, the CC domain was necessary for the oncogenic function of RNF214 in HCC. Taken together, our data favored that phase separation of RNF214 promoted the progression of HCC. RNF214 may be a potential biomarker and therapeutic target for HCC.

Abstract This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case–control study was conducted, and high-throughput sequencing of the V4–V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.

The investigation was motivated by the widespread use of ultra-high-strength steels in cable-stayed bridges and armor steel plates. These structures are exposed to elevated risks from extreme loads, including vehicle impacts and blast loadings. The study aimed to investigate the mechanical properties of 1770 steel for applications in extreme conditions. The strain rates and temperatures ranged from 0.00095 s−1 to 1303 s−1 and 20 °C–900 °C, respectively. Tensile tests were conducted at various strain rates using a Split Hopkinson Tension Bar for dynamic testing and a universal testing machine for quasi-static testing at room temperature (20 °C). Quasi-static tension at elevated temperatures was carried out using an electromechanical testing machine coupled with a heating device. A uniform temperature distribution inside the specimens was ensured by a 30-min holding time. The results of the tensile test indicate that the 1770 steel displays notable thermal softening effects and strain rate hardening that differ from mild steel. The standard Johnson-Cook (J-C) model was found to be inadequate in accurately predicting the strain rate effects of this specimen. To address this issue, the strain rate parameter C in the standard model was adjusted to create the modified J-C model, which demonstrated good agreement with the experimental results. To further demonstrate the modified model and the identified parameters, drop hammer impact tests and corresponding numerical simulations were conducted. The impact test and numerical simulation results showed good agreement in terms of deformation and contact force. The mechanical properties and the constitutive models can serve as a design reference for the ultra-high-strength 1770 steel in extreme envirnments, as well as a theoretical basis for fitting material models of similar ultra-high-strength steels.

Abstract Background This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). Methods This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. Results A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. Conclusions Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. Trial Registration ISRCTN34355813. Registered on 25/01/2021.

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

Cervical mucus not only provides energy for sperm but also forms a barrier to block sperm. This paper aims to study the microstructure of cervical mucus in dairy cows during the proestrus, estrus, and metestrus and its effect on sperm permeability. The experiment collected cervical mucus from 60 Holstein cows during these phases, then observed the different shapes of the mucus after crystallization, classified the mucus, and analyzed its proportions. Scanning electron microscopy was used to observe the ultrastructure of the cervical mucus and measure the micro-pore sizes, followed by sperm permeability tests using mucus from different estrous stages and counting the number of permeated sperm. The results indicate that cervical mucus from cows in different estrous phases includes four types (L, S, P, G), with each type constituting a different proportion. During the proestrus, the L type was significantly more prevalent than the other types (p < 0.05); during estrus, the S type was significantly more prevalent than the other types (p < 0.05); and during the metestrus, the p type was significantly more prevalent than the other types (p < 0.05). The micro-pore sizes of the same type of cervical mucus did not show significant differences across different estrous phases (p > 0.05). However, within the same estrous phase, there were significant differences in the micro-pore sizes among the four types (p < 0.05). The number of sperm that permeated the cervical mucus during estrus and metestrus was significantly higher than during the proestrus (p < 0.05). This study provides data support for the research on cervical mucus in dairy cows.

Nobiletin (NOB) is one of the major polymethoxyflavone in citrus peels, which has antioxidant activities. The purpose of this study was to investigate the effects of NOB on hypoxia-induced placental oxidative stress and its mechanism. In vitro experiments, JEG-3 hypoxic model was constructed, and treated with 100 μM NOB. In vivo experiment, pregnant rats were injected intraperitoneally with 50 mg/kg body weight NOB daily, and the placental hypoxia model was established by RUPP. NOB hampered the reducing of reducing power in hypoxic cells, promoted NADPH to provide hydrogen donors to regenerate antioxidants GPX and GSH, thereby promoting the decomposition of ROS. NOB alleviated the adverse reaction of hypoxic placental one-carbon metabolism disorder by regulating the levels of homocysteine, DNMTs and TETs. Moreover, NOB suppressed offspring brain damage induced by RUPP. Taken together, NOB attenuated hypoxia-induced placental redox perturbation and subsequent offspring brain injury by modulating one-carbon metabolism.

The epidermal growth factor receptor (EGFR) is the most frequently altered gene in glioblastoma (GBM), which plays an important role in tumor development and anti-tumor immune response. While current molecular targeted therapies against the EGFR signaling pathway and its downstream key molecules have not demonstrated favorable clinical outcomes in GBM. Whereas tumor immunotherapies, especially immune checkpoint inhibitors, have shown durable antitumor responses in many cancers. However, the clinical efficacy is limited in patients carrying EGFR alterations, indicating that EGFR signaling may involve tumor immune response. Recent studies reveal that EGFR alterations not only promote GBM cell proliferation but also influence immune components in the tumor microenvironment (TME), leading to the recruitment of immunosuppressive cells (e.g., M2-like TAMs, MDSCs, and Tregs), and inhibition of T and NK cell activation. Moreover, EGFR alterations upregulate the expression of immunosuppressive molecules or cytokines (such as PD-L1, CD73, TGF-β). This review explores the role of EGFR alterations in establishing an immunosuppressive TME and hopes to provide a theoretical basis for combining targeted EGFR inhibitors with immunotherapy for GBM.

Abstract Background Acute gouty arthritis (AGA) is an inflammatory arthritis clinically characterized by severe pain, swelling, and restricted movement of joints, which may cause physical disability and decrease quality of life. The use of recommended first-line treatment agents for AGA may be limited by adverse events. There has been a traditional use of alternative therapies for AGA. Tibetan medicine Qingpeng ointment is one of the on-market herbal products used for symptom relief of AGA. Previous clinical studies indicated that Qingpeng ointment can relieve pain, swelling, redness, and dysfunction of joints in patients with AGA. However, there is no rigorous randomized trial to demonstrate its benefit for AGA. In order to evaluate the efficacy and safety of Qingpeng ointment for AGA, we designed a randomized controlled trial. Methods This study is designed as a multi-center, randomized, double-blind, placebo-controlled trial. Two hundred and six adults with acute flare of gout, and visual analogue scale (VAS) score of joint pain ≥ 3 points will be recruited. Participants will be randomly assigned to herbal treatment or placebo group at a ratio of 1:1. Qingpeng ointment, or equal placebo ointment, will be applied topically at involved joints twice a day for consecutive 7 days. Patients in both groups would be allowed giving diclofenac sodium sustained-release tablets as rescue therapy when VAS score of joint pain ≥ 7 points during the treatment. The primary outcomes will be joint pain measured by VAS score, and joint swelling measured using width and thickness of affected joints and VAS score. Other outcome measures will be joint mobility, joint redness, C-reactive protein, serum uric acid, and the use of rescue medicine as well as adverse effect. Discussion To the best of our knowledge, this study is the first multi-center, randomized, double-blind, and placebo-controlled clinical trial to assess the efficacy of Tibetan medicine Qingpeng ointment for AGA. The findings of this study would provide evidence for its use to relieve symptoms of AGA. Trial registration ISRCTN ISRCTN34355813 . Registered on 25 January 2021

AIM: To analyze the protective effect of resveratrol on the optic nerve of glaucoma rats and its effect on the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)signal pathway and its related factors.METHODS: SPF grade SD rats were used to cauterize the scleral surface veins to make a right eye glaucoma model. After successful modeling, different doses(10, 20, 40 mg/kg intraperitoneal injection)of resveratrol were used to intervene. Intraocular pressure was measured 2h after the last administration, and retinal slices were made to observe the survival of retinal ganglion cells(RGC). Retinal plaque to observe the survival of retinal ganglion cells(RGC). Real-time fluorescence quantitative PCR and Western blot were used to detect the mRNA and protein expression of retinal PI3K, Akt, basic fibroblast growth factor(bFGF), and brain-derived neurotrophic factor(BDNF).RESULTS: The intraocular pressure(30.25±4.25)mmHg in the model group was higher than that in the low-dose group(26.30±4.05)mmHg, the middle dose group(22.31±3.68)mmHg and the high dose group(18.32±3.21)mmHg, and the model group RGC labeling rate(48.25±4.50)% was lower than the low dose group(56.32±5.05)%, middle dose group(66.03±6.68)% and high dose group(78.56±7.82)%(P

With the development of modern cities, the demand for cleaning glass curtain walls in urban skyscrapers is increasing, and therefore, many researches on facade cleaning robots have been carried out in the past few decades. In this article, a novel type of facade cleaning robot based on four-ducted fan is proposed. To improve the load capacity of the robot, the lifting and horizontal movement are, respectively, supported by an independent lifting mechanism and a lateral movement mechanism. Unlike the previous passive and active suction, the powerful suction power of the robot is provided by the four-ducted fan. Meanwhile, the obstacle-climbing force is caused by the forward of the four-ducted fan that improves the crossing obstacle ability. In addition, an incremental sliding mode algorithm is applied for controlling the posture when the robot crosses obstacles, which can ensure the stable performance of the cleaning robot under disturbance. Some simulations and experiments are conducted and the results demonstrate the effectiveness and robustness of the designed facade cleaning robot.

Background/Aims. Sexual differences exist in endothelial progenitor cells (EPCs), and various cardiovascular risk factors are associated with the preservation of endothelial function in premenopausal women. However, it is unclear whether differences in endothelial function and circulating EPCs exist between overweight premenopausal women and age-matched men. Methods. We compared EPC counting and functions in normal-weight and overweight premenopausal women and men, evaluated endothelial function in each group, and detected the expression of the guanosine triphosphate cyclohydrolase I (GTPCH I) pathway. Results. The number of EPCs was lower in the male group than in the female group, regardless of normal-weight or overweight status, and there was no significant difference between the different weight groups among females or males. Endothelial function and EPC migration and proliferation were preserved in overweight premenopausal women compared with overweight men as were nitric oxide (NO) levels in plasma and secreted by EPCs. Endothelial function, the circulating EPC population, and NO levels were not different between normal-weight and overweight premenopausal women. Flow-mediated dilatation was significantly correlated with EPC function, plasma NO levels, and EPC-secreted NO. Conclusions. This investigation provides the first evidence for sex-based differences in EPC activity and endothelial function in overweight middle-aged individuals; these differences are associated with alterations in NO production and may partly occur through downregulation of the GTPCH I pathway. The present results provide new insights into the mechanism underlying the preserved endothelial function in overweight premenopausal women and may uncover a potential therapeutic target for endothelial repair in overweight population.

An electromagnetic coupling mathematical model is established by finite element method and is verified by the contrastive experiments of copper matrix Ni–TiN cylindrical coating electrode, copper electrode and Cu50W electrode. The wear mechanism of Ni–TiN/Cu composite electrode in the case of high-frequency pulse current is studied, and the influence of the fluctuation frequency of discharge current on electrode wear in micro-EDM is found out. Compared with the electrode made from homogeneous material, the high frequency electromagnetic properties of Ni–TiN composite layer can be used effectively to inhibit the effect of high frequency pulse on the electrode and improve the distribution trend of current density.

In this study, we sequenced and annotated the nearly complete mitochondrial genome (mitogenome) of Sitona callosus (Coleoptera: Curculionidae). This mitogenome was 14,333 bp long and encoded 13 protein-coding genes, 19 transfer RNA genes (tRNAs), and two ribosomal RNA unit genes. Gene rearrangements were presented in a tRNA cluster of six tRNAs between nad3 and nad5, i.e. the ancestral order ARNSEF was changed to be RNSAEF. All tRNAs had a typical secondary cloverleaf structure, except for trnS1 which lacked the dihydrouridine arm. The Bayesian phylogenetic tree of 11 Entiminae species based on the concatenated nucleotide sequences of 13 PCGs showed that S. callosus and S. lineatus formed a clade which was at the basal position in the Entiminae phylogeny.

Here, we determined the complete mitogenome sequence of Sympiezomias velatus (Coleoptera: Curculionidae: Entiminae). This mitogenome was 15,592 bp long with an A + T content of 74.1% and contains 13 protein-coding genes (PCGs), 21 transfer RNA genes (tRNAs), 2 ribosomal RNA unit genes and a large non-coding region (putative control region). The trnI gene was not found in the S. velatus mitogenome. The order and orientation of the mitochondrial genes were identical to the inferred ancestral arrangement of insects except for trnR which was changed to be adjacent the nad3 gene. All tRNAs had the typical cloverleaf structure, except for trnS1 which lacked the dihydrouridine arm. The Bayesian phylogenetic tree of 10 Entiminae species based on the concatenated nucleotide sequences of 13 PCGs strong supported a sister relationship of S. velatus and Barynotus obscures.

In this study we sequenced and annotated the nearly complete mitochondrial genome (mitogenome) of Taiwania circumdata (Coleoptera: Chrysomelidae: Cassidinae), an important insect pest on sweetpotato and water spinach in Southern China. This mitogenome was 13,546 bp long and encoded 13 protein-coding genes (PCGs), 19 transfer RNA genes (tRNAs) and 2 ribosomal RNA unit genes. The T. circumdata mitogenome with an A + T content of 77.9% presented a positive AT-skew (0.126) and a negative GC-skew (−0.160). Eleven PCGs started with a typical ATN codon, whereas the remaining two PCGs used TTG (nad1) and AAT (cox1) as the initial codon. All the 19 tRNAs had a typical secondary cloverleaf structure, except for trnS1 (AGN) which lacked the dihydrouridine arm. Phylogenetic analyses using Bayesian inference and maximum likelihood methods based on the concatenated nucleotide sequences of 13 PCGs recovered a phylogeny of Bruchinae+ ((Galerucinae + Chrysomelinae) + (Criocerinae + Cassidinae)). In Cassidinae, T. circumdata and Laccoptera ruginosa formed a clade, which was sister to three Cassida species.

Hepatocellular cancer (HCC) is a lethal malignancy with poor prognosis and easy recurrence. There are few agents with minor toxic side effects that can be used for treatment of HCC. Evodiamine (Evo), one of the major bioactive components derived from fructus Evodiae, has long been shown to exert anti-hepatocellular carcinoma activity by suppressing activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). In addition, in the Nucleotide-Binding Oligomerization Domain 1 (NOD1) pathway, NOD1 could initiate NF-κB-dependent and MAPK-dependent gene transcription. Recent experimental studies reported that the NOD1 pathway was related to controlling development of various tumors. Here we hypothesize that Evo exerts anti-hepatocellular carcinoma activity by inhibiting NOD1 to suppress NF-κB and MAPK activation. Therefore, we proved the anti-hepatocellular carcinoma activity of Evo on HCC cells and detected the effect of Evo on the NOD1 pathway. We found that Evo significantly induced cell cycle arrest at the G2/M phase, upregulated P53 and Bcl-2 associated X proteins (Bax) proteins, and downregulated B-cell lymphoma-2 (Bcl-2), cyclinB1, and cdc2 proteins in HCC cells. In addition, Evo reduced levels of NOD1, p-P65, p-ERK, p-p38, and p-JNK, where the level of IκBα of HCC cells increased. Furthermore, NOD1 agonist γ-D-Glu-mDAP (IE-DAP) treatment weakened the effect of Evo on suppression of NF-κB and MAPK activation and cellular proliferation of HCC. In an in vivo subcutaneous xenograft model, Evo also exhibited excellent tumor inhibitory effects via the NOD1 signal pathway. Our results demonstrate that Evo could induce apoptosis remarkably and the inhibitory effect of Evo on HCC cells may be through suppressing the NOD1 signal pathway in vitro and in vivo.

OBJECTIVE: The present study aimed to investigate the relationship between obesity and mortality in patients with community-acquired pneumonia (CAP) in China. METHODS: In total, 909 patients with CAP were recruited for this study from January 2010 to June 2015. All patients were selected and divided into 4 groups according to their body mass index (BMI) values. All patients’ clinical information was recorded. The associations among mortality; BMI; the 30-day, 6-month and 1-year survival rates for different BMI classes; the etiology of pneumonia in each BMI group; and the risk factors for 1-year mortality in CAP patients were analyzed. RESULT: With the exception of the level of C-reactive protein (CRP), no other clinical indexes showed significant differences among the different BMI groups. No significant differences were observed among all groups in terms of the 30-d and 6-month mortality rates (p>0.05). There was a significantly lower risk of 1-year mortality in the obese group than in the nonobese group, (p

This study explored the active ingredients and mechanism of Pleurotus placentodes extract (PP-a) in alleviating acute liver injury. According to un-targeted metabolomics analysis, 102 compounds were identified in PP-a, 32 were regarded as active compounds for treating liver injury. PP-a’s targets (203) were observed for liver injury by network pharmacology analysis. Animal tests showed that PP-a significantly reduce inflammatory factors, increase anti-oxidative effects, and repair injured liver tissues, further effectively improving liver function. In addition, the mRNA expression of PTGS2 and NR3C1 was significantly reduced, while the mRNA expression of PPARA was significantly increased in CCl4-induced mice as a result of PP-a. These results suggest that P. placentodes exerts hepatoprotective effects probably by regulating the mRNA expression of PTGS2, NR3C1 and PPARA. For PP-a, L-Histidine, N-Acetyl-D-alloisoleucine, 15-OxoEDE and palmitic acid probably play a critical role in protecting against liver injury in CCl4-indcued mice.