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Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R‐induced upregulation of miR‐210, a hypoxia‐responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR‐210 in regulating the effects of isoflurane preconditioning on OGD/R‐induced cardiomyocyte injury, AC16 cells were transfected with anti‐miR‐210 or control anti‐miRNA. Results showed that isoflurane preconditioning attenuated OGD/R‐induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK‐MB levels), which could be reversed by anti‐miR‐210. Isoflurane preconditioning also prevented OGD/R‐induced increase in apoptotic rate, caspase‐3 and caspase‐9 activities, and Bax level and decrease in Bcl‐2 expression level, while anti‐miR‐210 blocked these effects. We also found that anti‐miR‐210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R‐induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p‐DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR‐210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR‐210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R‐induced cardiac cytotoxicity by regulating the miR‐210/BNIP3 axis. Isoflurane preconditioning elicited cardioprotection against OGD/R‐induced cardiomyocyte injury via maintaining mitochondrial function by regulating the miR‐210/BNIP3 axis. Our study provided new evidence for the underlying molecular mechanisms of protective effects of isoflurane preconditioning against OGD/R‐induced injury in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)‐induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ‐induced psoriasis‐like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin‐draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin‐draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor‐β (TGFβ) messenger RNA (mRNA) and interleukin‐23 (IL‐23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFβ/PU.1/IL‐23 signal axis. Significance statement: In this study, we explore the regulatory mechanism of Yinxieling (YXL), a clinically effective Chinese herbal medicine, on the differentiation and functions of langerhans cells (LCs) in psoriasis‐like mice. As the results show, YXL significantly alleviates psoriasis‐like skin inflammation induced by IMQ in mice. Although it has no obvious effect on dendritic cells in skin‐draining lymph nodes, it can significantly reduce the expression of LCs and PU.1+LCs in skin lesions, as well as inhibits the migration and maturation of LCs, and prevent its antigen presentation so as to effectively alleviate the psoriasis‐like skin inflammation on mice. Our investigation provides experimental basis to better understand the mechanism of traditional herbal medicine for psoriasis. [ABSTRACT FROM AUTHOR]

BackgroundMany app-based interventions targeting women with breast cancer have been developed and tested for effectiveness. However, information regarding the evaluation of the usage of these interventions is scarce. A better understanding of usage data is important to determine how women use apps and how these interventions affect health outcomes. ObjectiveThis study aimed to examine the usage duration and login frequency of an app-based intervention, the Breast Cancer e-Support (BCS) program, and to investigate the association between usage data and participants’ demographic and medical characteristics. MethodsThis study is a secondary data analysis of a randomized controlled trial assessing the effectiveness of the BCS program. The BCS program contains four modules: Learning Forum, Discussion Forum, Ask-the-Expert Forum, and Your Story Forum. A total of 57 women in the intervention group accessed the BCS program during their 12-week chemotherapy. The app’s background system tracked the usage duration and login frequency for each forum and the entire BCS program. ResultsThe total usage duration per participant ranged from 0 to 9371 minutes, and the login frequency per participant ranged from 0 to 774 times. The Discussion Forum and the Learning Forum were the most frequently used modules. The general linear model showed that age, education, family monthly income, and employment were associated with BCS usage duration and/or login frequency. Age (F1,45=10.09, P=.003, B=115.34, 95% CI 42.22-188.47) and education level (F1,45=7.22, P=.01, B=1949.63, 95% CI 487.76-3411.50) were positively associated with the usage duration of the entire BCS program. Family monthly income was positively associated with the usage duration of the Learning Forum (F1,45=11.85, P=.001, B=1488.55, 95% CI 617.58-2359.51) and the login frequency of the entire BCS program (F1,45=4.47, P=.04, B=113.68, 95% CI 5.33-222.03). Employment was negatively associated with the usage duration of the Ask-the-expert Forum (F1,45=4.50, P=.04, B=–971.87, 95% CI –1894.66 to –49.07) and the Your Story Forum (F1,45=5.36, P=.03, B=–640.71, 95% CI –1198.30 to –83.11) and positively associated with the login frequency of the entire BCS program (F1,45=10.86, P=.002, B=192.88, 95% CI 75.01-310.74). No statistical differences were found between BCS usage data and cancer stage, BMI, comorbidity, types of surgery, or cycles of chemotherapy. ConclusionsOverall, this study found considerable variability in the usage of app-based interventions. When health care professionals incorporate app-based interventions into their routine care for women with breast cancer, the learning and discussion functions of apps should be strengthened to promote engagement. Additionally, characteristics of women with breast cancer, such as age, level of education, income, and employment status, should be taken in consideration to develop tailored apps that address their particular needs and therefore improve their engagement with the app. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12616000639426; http://www.ANZCTR.org.au/ACTRN12616000639426.aspx

N2 electroreduction reaction (NRR) enables an eco‐friendly NH3 synthesis under mild conditions, which is regarded as a carbon‐neutral alternative technology to the traditional Haber–Bosch process. However, its practical applications are seriously impeded by the difficulty in N2 adsorption and activation over catalysts, as well as the competing hydrogen evolution reaction (HER). In this work, a novel bismuth molybdate nanocatalyst with sufficient oxygen vacancies and high Biconcentration (41.9 at%), BiMoO‐OVs, is synthesized and demonstrated as an excellent NRR electrocatalyst. Benefiting from synergistic effect of the adequate Bi active centers with inert HER activity provided by the high concentration of Bi, and the reinforced N2 adsorption and activation ability of oxygen vacancies, the as‐synthesized BiMoO‐OVs presents a high Faradaic efficiency of 16.38% with a NH3 yield rate of 3.65 µg h−1 cm−2 at −0.4 V (vs RHE) in neutral electrolyte, which outperforms those of most Bi‐based NRR nanocatalysts. Noticeably, it also presents excellent electrochemical durability for at least 24 h. The present work provides a simple and effective strategy for designing low‐cost and high‐performance Bi‐based catalysts. [ABSTRACT FROM AUTHOR]

Among gynecological malignancies, ovarian cancer has the highest mortality rate and has sparked widespread interest in studying the mechanisms underlying ovarian cancer development. Based on TCGA and GEO databases, we investigated the highly expressed autophagy‐related genes that determine patient prognosis using limma differential expression and Kaplan–Meier survival analyses. The biological processes associated with these genes were also predicted using GO/KEGG functional enrichment analysis. CCK‐8, cell scratch, and transwell assays were used to investigate the effects of PXN on the proliferation, migration, and invasion abilities of ovarian cancer cells. Transmission electron microscopy was used to observe the autophagosomes. The expression of autophagy proteins and the PI3K/Akt/mTOR and p110β/Vps34/Beclin1 pathway proteins in ovarian cancer cells was detected using western blot; autophagy protein expression was further detected and localized using cellular immunofluorescence. A total of 724 autophagy‐related genes were found to be overexpressed in ovarian ‐cancer tissues, with high expression of PEX3, PXN, and RB1 associated with poor prognosis in patients (p <.05). PXN activates and regulates signaling pathways related to cellular autophagy, ubiquitination, lysosomes, PI3K‐Akt, and mTOR. Autophagosomes were observed in all cell groups. The increase in PXN gene expression promoted the proliferation, migration, and invasion of ovarian cancer cells, increased the expression of SQSTM1/p62 protein, decreased LC3II/LC3Ⅰ, inhibited the phosphorylation of Akt and mTOR proteins, and suppressed the expression of PI3K(p110β) and Beclin1 proteins. The decrease in PXN expression also confirmed these changes. Thus, PXN is highly expressed during ovarian cancer and is associated with poor patient prognosis. It may promote ovarian cancer cell proliferation, migration, and invasion by inhibiting cellular autophagy via suppression of the p110β/Vps34/Beclin1 pathway. Significance statement: The described experimental study not only provides an important theoretical basis for new therapeutic tools and targets for metastatic ovarian cancer, but also has great potential for the development of adjuvant therapies for ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body's adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors. Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated. Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group. Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients. [ABSTRACT FROM AUTHOR]

Objective: Polo‐like kinase 1 (PLK1), a serine/threonine‐protein kinase, functions as a potent oncogene in the initiation and progression of tumor. The aim of this study is to assess potential correlations between PLK1 expression and immune infiltration in breast cancer (BRCA) and construct a PLK1‐based immune risk model applicable for prognosis and treatment response prediction in BRCA. Methods: We collected data on PLK1 gene expression in BRCA patients from The Cancer Genome Atlas (TCGA) database. Thereafter, we analyzed the associations of PLK1 expression with immune cell infiltration and immunomodulators, and established a prognostic risk model based on seven PLK1‐associated immunomodulator genes and a nomogram for survival prediction. Results: BRCA prognosis, clinical stage progression, and tumor classification were all shown to be substantially correlated with PLK1 expression. The PLK1 gene was significantly enriched in T cell and B cell receptors and molecules of the chemokine signaling pathways. Specifically, PLK1 expression was positively correlated with the CD8+ T cell and regulatory T cell (Tregs) activation and negatively correlated with M2 macrophage infiltration. The seven‐genes‐based risk model could serve as an independent prognostic factor of BRCA. The risk model was markedly correlated with the expression of programmed cell death protein 1/programmed cell death ligand 1 (PD‐1/PD‐L1; both p < 0.001) immune checkpoints, and tumor mutation burden (TMB). High‐ and low‐risk BRCA patients identified by the risk model responded differently to anti‐PD‐1 and/or anti‐CTLA4 therapy, as well as common chemotherapy drugs, like cisplatin, paclitaxel, and gemcitabine. Conclusion: This PLK1‐based immune risk model can effectively predict the prognosis and tumor progression of BRCA, identify gene mutations, and evaluate patient's response toward immunotherapy and chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Background. Lymphatic metastasis is a common phenomenon of cervical cancer. Tumor necrosis factor-α (TNF-α) was found to be closely associated with lymphatic cancer metastasis. However, the mechanism through which TNF-α regulates lymphatic metastasis in cervical cancer remains unclear. Methods. In this study, cervical cancer cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with or without TNF-α for 48 h, and then the corresponding conditional medium (CM-TNF-α or CM) was collected. The level of vascular endothelial growth factor (VEGFC) in the corresponding CM was then detected using an enzyme-linked immunosorbent assay (ELISA). Next, human lymphatic endothelial cells (HLECs) were cultured in CM-TNF-α or CM for 48 h. Cell viability was measured using the cell counting kit-8 (CCK-8) assay, and angiogenesis was detected using a tube formation assay. Subsequently, the expressions of AKT, p-AKT, ERK, and p-ERK in HLECs were detected using western blotting. In addition, to further investigate the effect of TNF-α on the progression of cervical cancer, a C33A subcutaneous xenograft model was established in vivo. Results. We found that TNF-α significantly stimulated cervical cancer cells to secrete VEGFC. Additionally, the CM collected from the TNF-α-treated cervical cancer cells notably promoted the proliferation, migration, and angiogenesis of HLECs; however, these changes were reversed by MAZ51, a VEGFR3 inhibitor. Moreover, TNF-α obviously elevated D2-40 and VEGFC protein expressions in tumor tissues, promoting lymphangiogenesis and lymphatic metastasis in vivo. Meanwhile, TNF-α markedly upregulated p-AKT and p-ERK expressions in tumor tissues, whereas these changes were reversed by MAZ51. Conclusion. Collectively, TNF-α could promote tumorigenesis, lymphangiogenesis, and lymphatic metastasis in vitro and in vivo in cervical cancer via activating VEGFC-mediated AKT and ERK pathways. These results may provide new directions for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

The pollution of ammonia-nitrogen in water became more serious with the development of the industry. In this paper, hydroxyapatite (HAP) was prepared from waste fish scales; the XRD, FTIR, SEM, TEM and Raman were used to characterize the prepared samples, and the prepared HAP samples were studied as degradation photocatalyst and adsorbing material for the removal of ammonia-nitrogen. The ammonia-nitrogen removal efficiency (ANRE, Removal Rate = (Initial Concentration–Current Concentration)/Initial Concentration × 100%) of the samples was also discussed. The results showed that the HAP sample, which was calcinated at 800 °C for 2 h, had the best ANRE, which was 41%. The UV-Vis, EIS, and PL were used to analyze the reason for the different ANRE. The reason for the high ANRE was attributed to the samples' superior adsorption capability resulting from their large specific surface area, as well as their superior properties for photocatalytic degradation. This was a meaningful work to explore a treatment of ammonia-nitrogen by HAP. [ABSTRACT FROM AUTHOR]

Intrauterine adhesion (IUA) is a gynaecological disease caused by uterine cavity surgeries and infections that leads to partial or total occlusion of the uterine cavity. However, the underlying mechanism(s) and progression of the disease have not yet been identified. IUA has a high recurrence rate and poor prognosis, and effective drugs to prevent adhesion are lacking. Therefore, establishing an effective animal model of IUA is of great significance for revealing the pathogenesis of IUA and the mechanism(s) governing drug effects. Rats, mice, rabbits, and other animals are currently used to establish intrauterine adhesion models. The IUA induction methods include chemical, thermal, or mechanical damage and mechanical damage combined with an infective method. We analysed the advantages and disadvantages of various models and their clinical simulations in order to provide a precise animal model for exploring the pathogenesis, treatment strategies, and prevention of IUA. [ABSTRACT FROM AUTHOR]

Electrocatalytic N 2 reduction reaction (NRR) is of great potential as a sustainable and alternative technique to the energy-intensive Haber-Bosch process for NH 3 production. However, its practical applications are impeded by the low NH 3 yield and Faradaic efficiency (FE) mainly due to the inert N≡N triple bond and the competing hydrogen evolution reaction (HER). Herein, ruthenium-doped defect-rich SnO 2 nanoparticles on carbon cloth (Ru–SnO 2 /CC) are synthesized for efficient electrocatalytic NRR under ambient conditions. The catalysts exhibit an NH 3 yield of 4.83 μg h−1 cm−2 with a FE of 17.01% at −0.2 V vs. reversible hydrogen electrode in 0.1 M Na 2 SO 4. The integration of Ru species, SnO 2 and oxygen vacancies leads a synergistic catalytic system, in which the semiconducting SnO 2 particles not only stabilize the Ru active centers but also suppress the HER, while the oxygen vacancies in SnO 2 lattice help to promote the N 2 adsorption and enhance the activity of the Ru active centers. Overall, this synergy result in a unique local environment around the Ru active sites that favors the NRR process, which is further reinforced by the binder-free and facile electron transfer nature of CC, leading to the outstanding NRR catalytic activity and durability. These results outperform majority of the noble-metals-based electrocatalysts under similar conditions. This metal-doping tuned local environment manipulation may open up a promising avenue to the design and fabrication of efficient catalysts for N 2 electroreduction. A self-supporting electrocatalyst, Ru–SnO 2 /CC, exhibits excellent performance in neutral electrolyte towards N 2 electroreduction due to the synergistic effect provided by Ru active centers, SnO 2 , oxygen vacancies and carbon cloth. [Display omitted] • Ru doped defect-rich SnO 2 nanoparticles decorated on carbon cloth are successfully fabricated. • Ru–SnO 2 /CC exhibits outstanding activity and selectivity towards N 2 electroreduction. • The crucial roles of engineering local environment are systematically investigated. [ABSTRACT FROM AUTHOR]

Paraquat (PQ) has high acute toxicity, even at low concentrations. For most people, the main pathway of exposure to PQ is through the diet. Therefore, the development of simple and efficient methods for PQ testing is critical for ensuring food safety. In this study, a new electrochemical detection strategy for paraquat is proposed based on the specific binding of PQ to its nucleic acid aptamer. Firstly, the Zn/Fe bimetallic ZIF derived nanoporous carbon (Zn/Fe-ZIF-NPC) and nickel hexacyanoferrate nanoparticles (NiHCF-NPs) were sequentially modified onto the glassy carbon electrode (GCE). NiHCF-NPs served as the signal probes, while Zn/Fe-ZIF-NPC facilitated electron transfer and effectively enhanced the sensing signal of NiHCF-NPs. Au nanoparticles (AuNPs) were then electrodeposited on the NiHCF-NPs/Zn/Fe-ZIF-NPC/GCE and then the thiolated aptamer was assembled on the AuNPs/NiHCF-NPs/Zn/Fe-ZIF-NPC/GCE via Au-S bonding. When incubated with PQ, the formation of PQ–aptamer complexes delayed the interfacial electron transport reaction of NiHCF-NPs, which caused a decrease in the current signals. As a result, simple and highly sensitive detection of PQ can be readily achieved by detecting the signal changes. A linear range was obtained from 0.001 to 100 mg/L with a detection limit as low as 0.34 μg/L. Due to the recognition specificity of the aptamer to its target molecule, the proposed method has excellent anti-interference ability. The prepared electrochemical aptasensor was successfully used for PQ assay in lettuce, cabbage and agriculture irrigation water samples with recoveries ranging from 96.20% to 104.02%, demonstrating the validity and practicality of the proposed method for PQ detection in real samples. [ABSTRACT FROM AUTHOR]

Four actinomycete strains isolated from the coral Acropora austera and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from Streptomyces diacarni SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A–B (1–2), chlocarbazomycin E (3), and brocarbazomycin A (4), together with three known chlocarbazomycins A–C (5–7) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds 1 and 2 have the rare sulfur-containing carbazole nuclei, and 3 and 4 contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns. [ABSTRACT FROM AUTHOR]

Herein, a method of ultrasound treatment combined with surfactant aqueous phase dispersion was proposed for the extraction of high-purity gutta-percha in its native state from enzymatic hydrolyzed Eucommia ulmoides pericarps. Firstly, the plant tissues wrapped around gutta-percha were destructed through enzymatic hydrolysis, then the plant tissues debris still attached to gutta-percha were further stripped off by ultrasound. Finally, under the "amphiphilic" action of sodium dodecyl sulfate (SDS), the entangled gutta-percha was untwined, allowing the residual plant tissue debris to be released and precipitated, thus high purity gutta-percha was obtained. The process parameters were optimized through single factor and response surface experiments. The optimal parameters for ultrasonic treatment were displayed as follows: frequency of 40 kHz, power of 320 W, time of 7.3 h, temperature of 50 °C, and material-to-liquid ratio of 1:70 g/mL, and for the aqueous phase dispersion of surfactant were SDS concentration 1.7%, temperature 80 °C, stirring speed 1200 rpm, solid-to-liquid ratio 1:60 g/mL, and time 60 h. Under optimal conditions, the purity of gutta-percha reached 95.4 ± 0.31% and its weight average molecular weight (Mw) was 20.85 × 104. Moreover, the obtained gutta-percha maintained its native filamentous form. The obtained products were characterized by IR, NMR, XRD, TGA, DSC, and tensile experiments, which showed that the obtained product was gutta-percha and maintained the natural α- and β- crystal structure. The proposed method overcomes the disadvantages of the traditional organic solvent method, which has great environmental pollution and destroys the gutta-percha structure. This is also the first reported method to obtain high purity gutta-percha while maintaining its native state. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is the leading cause of cardiovascular mortality, which is related to cardiac myocyte apoptosis. Butorphanol is an opioid receptor agonist with potential cardioprotective function. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)‐induced cardiomyocyte apoptosis. The overlapping targets of ischemic heart disease and butorphanol were analyzed according to GeneCards, ParmMapper, Cytoscape, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Human cardiomyocyte AC16 cells were incubated with butorphanol and then stimulated with OGD/R. Cell injury was investigated by Cell Counting Kit‐8, lactate dehydrogenase (LDH) assay kit, TUNEL staining, caspase‐3 activity assay kit, and Western blotting. The proteins in signaling pathways were measured using Western blotting. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple signaling pathways. Butorphanol alone showed little cytotoxicity to cardiomyocytes, and it protected against OGD/R‐induced viability inhibition, LDH release, cell apoptosis, and increase of caspase‐3 activity and expression levels of cleaved caspase‐3 and Bim. Butorphanol promoted the activation of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) and hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathways and attenuated the activation of the mitogen‐activated protein kinase (MAPK) signaling in OGD/R‐treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R‐induced cardiomyocyte apoptosis through activating the PI3K/Akt/FoxO and HIF‐1α/VEGF pathways and inactivating the MAPK pathway. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)‐induced cardiomyocyte apoptosis. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple pathways. Butorphanol protected against OGD/R‐induced apoptosis. Butorphanol promoted the PI3K/Akt/FoxO and HIF‐1α/VEGF pathways and attenuated the MAPK signaling in OGD/R‐treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R‐induced cardiomyocyte apoptosis through multiple pathways. [ABSTRACT FROM AUTHOR]

Electrocatalytic nitrogen reduction reaction (NRR) under ambient conditions is still seriously impeded by the inferior NH3 yield and low Faradaic efficiency, especially at low overpotentials. Herein, we report the synthesis of nano‐sized RuO2 and Bi2O3 particles grown on functionalized exfoliated graphene (FEG) through in situ electrodeposition, denoted as RuO2−Bi2O3/FEG. The prepared self‐supporting RuO2−Bi2O3/FEG hybrid with a Bi mass loading of 0.70 wt% and Ru mass loading of 0.04 wt% shows excellent NRR performance at low overpotentials in acidic, neutral and alkaline electrolytes. It achieves a large NH3 yield of 4.58±0.16 μgNH3 h−1 cm−2 with a high Faradaic efficiency of 14.6 % at −0.2 V versus reversible hydrogen electrode in 0.1 M Na2SO4 electrolyte. This performance benefits from the synergistic effect between Bi2O3 and RuO2 which respectively have a fairly strong interaction of Bi 6p orbitals with the N 2p band and abundant supply of *H, as well as the binder‐free characteristic and the convenient electron transfer via graphene nanosheets. This work highlights a new electrocatalyst design strategy that combines transition and main‐group metal elements, which may provide some inspirations for designing low‐cost and high‐performance NRR electrocatalysts in the future. [ABSTRACT FROM AUTHOR]

Objective: To explore the application effects of hierarchical, diversified soft skills training in clinical nursing training. Methods: This is a prospective study. There involved a total of 124 nurses who participated in the training in our hospital. The participants were randomly allocated to the study group and the control group, with 62 nurses in each group. Study group received hierarchical, diversified nursing soft skills training and control group received conventional nursing training only. The core competence, knowledge, operation skills and clinical competence of nurses in the two groups before and after training were measured and compared, and the satisfaction of doctors and patients in the two groups after training were observed. Results: The scores of education and consultation, professional development, legal and ethical practice, interpersonal relationship, leadership, clinical nursing and critical thinking were compared between the two groups before the training (P >.05). After the training, however, the scores of abovementioned items in the two groups were higher than those before treatment, and compared with the control group, the scores in the study group were significantly higher (P <.05). Before the training, the scores of theoretical knowledge, operation skills and clinical competence of nurses in the two groups were compared (P >.05). After training, the scores of those items of nurses in the two groups were higher than those before treatment. Compared with the control group, the scores of theory, operation skills and clinical competence of nurses in the study group were significantly higher (P <.05). Moreover, the study group showed significant higher satisfaction of doctors and patients (P <.05). Conclusion: Hierarchical, diversified soft skills training in clinical nursing training programme obtained better outcomes in the core competence, knowledge, operation skills and clinical competence of nursing staff, and promoted the satisfaction of doctors and patients, which can be utilised for clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objective: Opioid medications used to be the key method for the pain management after spine surgery; most of the opioids may cause many adverse reactions. The purpose of this research was to observe the role of dexmedetomidine combined with butorphanol in the pain management of patients after posterior spinal surgery. Methods: This research was conducted at the First Hospital Affiliated to Jinzhou Medical University, China from May 2018 to January 2019. Sixty patients who underwent posterior spinal surgery were equally divided into two groups randomly: Group B who received butorphanol 0.125 mg/kg and Group DB who received dexmedetomidine (DEX) 0.1 µg/kg/hour plus butorphanol (B) 0.125 mg/kg. The patient-controlled analgesia was conducted to deliver a bolus dose of 0.5 ml. followed by an infusion of 2 ml/hour and a lockout time of 15 minutes nutes. Heart rate, mean arterial pressure, respiration rate, pulse oxygen saturation, visual analog scale score (VAS), and Ramsay sedation score were recorded as follows: 1 hour (T1), 2 hours (T2), 6 hours (T3), 12 hours (T4), and 24 hours (T5) post-surgery. The total number of buttons pressing of patient controlled intravenous analgesia (PCIA) and supplementary analgesic agents was observed and adverse drug reactions and total rate of patient satisfaction were evaluated statistically. Results: VAS scores at different intervals in DB group were significantly lower compared with the B group after surgery; while the score of Ramsay sedation was remarkably higher in DB group. The total number of buttons pressing of PCIA was less than that of the B group and the frequency of nausea was notably lower in DB group (p < 0.05). The total rate of satisfaction with analgesia in DB group was higher after surgery. Conclusion: DEX could enhance the analgesic effect of butorphanol after posterior spinal surgery with lesser adverse reactions. [ABSTRACT FROM AUTHOR]

Isoflurane, one of the commonly used inhalation anesthetics worldwide in clinical practice, may generate substantial risks of neurotoxicity in the developing brains. The present study aimed to illustrate the effects and underlying mechanisms of miR-214 on isoflurane-induced neurotoxicity in human neuroblastoma cell line SH-SY5Y. SH-SY5Y cells were transfected with miR-214 or miR-con alone or in combination with pcDNA empty vector or pcDNA-PTEN in the presence of 3% isoflurane and incubated for 48 h. Cell viability, lactate dehydrogenase (LDH) release, apoptosis, and caspase-3/7 activity were evaluated using CCK-8, LDH release assay, flow cytometry analysis, and caspase-3/7 activity assay, respectively. The superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) activities were measured using commercial kits. miR-214 expression and alterations of the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway were detected by qRT-PCR and Western blot, respectively. The interaction between miR-214 and PTEN was explored by luciferase reporter assay. We found that isoflurane exposure induced neurotoxicity in SH-SY5Y cells, as evidenced by the reduced cell viability, increased LDH release, apoptotic rate, caspase-3/7 activity, and oxidative stress levels. Moreover, isoflurane exposure decreased the expression of miR-214 and affected the PTEN/PI3K/Akt pathway in SH-SY5Y cells. miR-214 overexpression significantly suppressed isoflurane-induced viability reduction, LDH release, apoptosis and oxidative stress, as well as inactivation of the PI3K/Akt pathway in SH-SY5Y cells. Interestingly, PTEN was identified as a target of miR-214. Moreover, PTEN upregulation blocked the effects of miR-214 on isoflurane-induced neurotoxicity in SH-SY5Y cells. In conclusion, miR-214 protected against isoflurane-induced neurotoxicity in SH-SY5Y cells via regulation of PI3K/Akt pathway by targeting PTEN, contributing to better understanding the underlying mechanisms of anesthetics-induce neurotoxicity. • miR-214 inhibits isoflurane-induced viability reduction and LDH release in SH-SY5Y cells. • miR-214 suppresses isoflurane-induced apoptosis of SH-SY5Y cells. • miR-214 attenuates isoflurane-induced oxidative stress and inactivation of PTEN/PI3K/Akt pathway. • PTEN is a target of miR-214 in SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to investigate the difference in disease severity between influenza A and B among hospitalized adults using a novel ordinal scale and existing clinical outcome end points. Methods A prospective, observational study was conducted over the 2016–2018 influenza seasons in a central hospital. The primary outcome was the rate of clinical improvement, defined as a decline of 2 categories from admission on a 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death), or hospital discharge up to day 28. Results In total, 574 eligible patients were enrolled, including 369 (64.3%) influenza A cases and 205 (35.7%) influenza B cases. The proportion of patients with a worse ordinal scale at admission was higher in influenza A than influenza B (P =.0005). Clinical improvement up to 28 days occurred in 82.4% of patients with influenza A and 90.7% of patients with influenza B (P =.0067). The Cox model indicated that influenza B patients had a higher clinical improvement probability than influenza A cases (adjusted hazard ratio [HR], 1.266; 95% confidence interval [CI], 1.019–1.573; P =.0335). A similar pattern was observed in weaning oxygen supplement (adjusted HR, 1.285; 95% CI, 1.030–1.603; P =.0261). In-hospital mortality for influenza A was marginally higher than influenza B (11.4% vs 6.8%; P =.0782). Conclusions Our findings indicated that hospitalized patients with influenza A were more ill and had delayed clinical improvement compared with those with influenza B virus infection. [ABSTRACT FROM AUTHOR]

MVIIA (ziconotide) is a specific inhibitor of N-type calcium channel, Cav2.2. It is derived from Cone snail and currently used for the treatment of severe chronic pains in patients unresponsive to opioid therapy. However, MVIIA produces severe side-effects, including dizziness, nystagmus, somnolence, abnormal gait, and ataxia, that limit its wider application. We previously identified a novel inhibitor of Cav2.2, ω-conopeptide SO-3, which possesses similar structure and analgesic activity to MVIIA's. To investigate the key residues for MVIIA toxicity, MVIIA/SO-3 hybrids and MVIIA variants carrying mutations in its loop 2 were synthesized. The substitution of MVIIA's loop 1 with the loop 1 of SO-3 resulted in significantly reduced Cav2.2 binding activity in vitro ; the replacement of MVIIA loop 2 by the loop 2 of SO-3 not only enhanced the peptide/Cav2.2 binding but also decreased its toxicity on goldfish, attenuated mouse tremor symptom, spontaneous locomotor activity, and coordinated locomotion function. Further mutation analysis and molecular calculation revealed that the toxicity of MVIIA mainly arose from Met 12 in the loop 2, and this residue inserts into a hydrophobic hole (Ile 300 , Phe 302 and Leu 305 ) located between repeats II and III of Cav2.2. The combinative mutations of the loop 2 of MVIIA or other ω-conopeptides may be used for future development of more effective Cav2.2 inhibitors with lower side effects. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, there has been a strong association between transient receptor potential (TRP) channels and the development of various malignancies, drug resistance, and resistance to radiotherapy. Consequently, we have investigated the relationship between transient receptor potential channels and cervical cancer from multiple angles. Methods: Patients' mRNA expression profiles and gene variants were obtained from the TCGA database. Key genes in transient receptor potential channel prognosis-related genes (TRGs) were screened using the least absolute shrinkage and selection operator (LASSO) regression method, and a risk signature was constructed based on the expression of key genes. Various analyses were performed to evaluate the prognostic significance, biological functions, immune infiltration, and response to immunotherapy based on the risk signature. Results: Our research reveals substantial differences between high and low-risk groups in prognosis, tumor microenvironment, tumor mutational load, immune infiltration, and response to immunotherapy. Patients in the high-risk group exhibited poorer prognosis, lower tumor microenvironment scores and reduced response to immunotherapy while showing increased sensitivity to specific targeted drugs. In vitro experiments further illustrated that inhibiting transient receptor potential channels effectively decreased the proliferation, invasion, and migration of cervical cancer cells. Discussion: This study highlights the significant potential of transient receptor potential channels in cervical cancer, emphasizing their crucial role in prognostic prediction and personalized treatment strategies. The combination of TRP inhibitors with immunotherapy and targeted drugs may offer promise for individuals affected by cervical cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Lin, Wu, Zheng, Cui, Cai, Li, Zheng and Sun.)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis is a clinically prevalent chronic progressive liver disease characterized by diffuse liver damage resulting from long-term or repeated actions of 1 or more etiological factors. However, the impact of CENPF and nuclear division cycle 80 (NDC80) genes on rehabilitation nursing of HCC and cirrhosis remains unclear. HCC and cirrhosis datasets GSE63898 and GSE89377 profile files were downloaded from the gene expression omnibus database generated on platforms GPL13667 and GPL6947, respectively. Differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), survival analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were conducted. Gene expression heatmaps were plotted. miRNAs regulating central DEGs were selected through TargetScan. A total of 626 DEGs were identified. According to gene ontology (GO) analysis, they were primarily enriched in small molecule metabolic processes, drug metabolic processes, binding of identical proteins, and lipid metabolic processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis results indicated that the target genes were mainly enriched in metabolic pathways, phagosomes, glycine, serine, and threonine metabolism. The construction and analysis of the PPI network revealed 3 core genes (NDC80, CENPF, RRM2). Gene expression heatmaps showed that core genes (CENPF, NDC80) were highly expressed in HCC and cirrhosis samples. CTD analysis found that 2 genes (CENPF and NDC80) were associated with liver, jaundice, ascites, fever, dyspepsia, and hepatic encephalopathy. CENPF and NDC80 are highly expressed in HCC and cirrhosis, and CENPF and NDC80 might be the biomarkers of rehabilitation nursing of HCC and cirrhosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cervical cancer (CC) remains one of the most common and deadly malignancies in women worldwide. FBXO5 , a protein-coding gene, is highly expressed in a variety of primary tumors and promotes tumor progression, however, its role and prognostic value in CC remain largely unknown. Methods: A key differential gene, FBXO5 , was screened according to WGCNA based on immunohistochemical assays of clinical samples, multiple analyses of the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, including survival analysis, tumor mutational burden, GO, KEGG, tumor immune infiltration, and chemotherapeutic drug sensitivity, to explore the expression and prognostic value of FBXO5 in CC. The migration and invasiveness of cervical cancer cells following FBXO5 knockdown and overexpression were examined using wound healing and transwell assays, and the viability of cancer cells was assessed using CCK8 and EdU assays. Results: FBXO5 was discovered to be substantially expressed in CC tissues using data from our CC cohort and the TCGA database, and a survival analysis indicated FBXO5 as a predictive factor for poor overall survival in CC patients. In vitro , CC cells were more inclined to proliferate, migrate, and invade when FBXO5 was upregulated as opposed to when it was knocked down., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jiang, Zheng, Cui, Li, Wu, Cai, Zheng and Sun.)