Effect of X-ray irradiation on renal excretion of bestatin through down-regulating organic anion transporters via the vitamin D receptor in rats.

Pharmacokinetic changes induced by radiation following radiotherapy ("RT-PK" phenomenon) are of great significance to the effectiveness and safety of chemotherapeutic agents in clinical settings. The aims of this study were to clarify the organic anion transporters (Oats) involved in the "RT-PK" phenomenon of bestatin in rats following X-ray irradiation and to elucidate its potential mechanism via vitamin D signalling. Pharmacokinetic studies, uptake assays using rat kidney slices and primary proximal tubule cells, and molecular biological studies were performed. Significantly increased plasma concentrations and systemic exposure to bestatin were observed at 24 and 48 h following abdominal X-ray irradiation, regardless of oral or intravenous administration of the drugs in rats. Reduced renal clearance and cumulative urinary excretion of bestatin were observed at 24 and 48 h post-irradiation in rats following intravenous administration. The uptake of the probe substrates p-aminohippuric acid and oestrone 3-sulfate sodium in vitro and the expression of Oat1 and Oat3 in vivo were reduced in the corresponding models following irradiation. Moreover, the upregulation of the vitamin D receptor (Vdr) in mRNA and protein levels negatively correlated with the expressions and functions of Oat1 and Oat3 following irradiation. Additionally, elevated plasma urea nitrogen levels and histopathological changes were observed in rats after exposure to irradiation. The "RT-PK" phenomenon of bestatin occurs in rats after exposure to irradiation, possibly resulting in the regulation of the expressions and activities of renal Oats via activation of the Vdr signalling pathway.

Assessment of drug-drug interaction of dapagliflozin with LCZ696 based on an LC-MS/MS method.

The co-administration of dapagliflozin (DPF) and sacubitril/valsartan (LCZ696) has emerged as a promising therapeutic approach for managing heart failure. Given that DPF and LCZ696 are substrates for P-glycoprotein, there is a plausible potential for drug-drug interactions when administered concomitantly. To investigate the pharmacokinetic changes when these drugs are co-administered, we have established and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method capable of simultaneously detecting DPF, LBQ657 (the active metabolite of sacubitril) and valsartan in rat plasma. This method has demonstrated selectivity, sensitivity, and accuracy. Drug-drug interactions were examined by the LC-MS/MS method. The mechanisms were investigated using everted intestinal sac models and Caco-2 cells. The results showed that DPF significantly increased the area under the curve (AUC(0-t)) (3,563.3 ± 651.7 vs. 7,146.5 ± 1,714.9 h µg/L) of LBQ657 (the active metabolite of sacubitril) and the AUC(0-t) (24,022.4 ± 6,774.3 vs. 55,728.3 ± 32,446.3 h µg/L) of valsartan after oral co-administration. Dapagliflozin significantly increased the amount of LBQ657 and valsartan in intestinal sacs by 1- and 1.25-fold at 2.25 h. Caco-2 cell uptake studies confirmed that P-glycoprotein is the transporter involved in this interaction. This finding enhances the understanding of drug-drug interactions in the treatment of heart failure and provides a guidence for clinical therapy.

The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.

NADPH oxidase, as a major source of intracellular reactive oxygen species (ROS), assumes an important role in the immune response and oxidative stress response of the body. NADPH 9 oxidase 2 (NOX2) is the first and most representative member of the NADPH oxidase family, and its effects on the development of tumor cells are gaining more and more attention. Our previous study suggested that NCF4 polymorphism in p40phox, a key subunit of NOX2, affected the outcome of diffuse large B-cell lymphoma patients treated with rituximab. It hypothesized that NOX2-mediated ROS could enhance the cytotoxic effects of some anti-tumor drugs in favor of patients with tumors. Several reviews have summarized the role of NOX2 and its congeners-mediated ROS in anti-tumor therapy, but few studies focused on the relationship between the expression of NOX2 and anti-tumor drug resistance. In this article, we systematically introduced the NOX family, represented by NOX2, and a classification of the latest inhibitors and agonists of NOX2. It will help researchers to have a more rational and objective understanding of the dual role of NOX2 in tumor drug resistance and is expected to provide new ideas for oncology treatment and overcoming drug resistance in cancer.

[Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models].

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

Comparisons of biometric parameters measurements by OPD-SCAN â ¢ and Pentacam in cataract.

BACKGROUND: Comparison of OPD-Scan III and Pentacam measurements of relevant parameters guiding the selection of multifocal intraocular lenses in cataract patients. METHODS: A retrospective study included 120 patients (120 eyes) with cataract. Their chord kappa, chord alpha, corneal spherical aberration, and pupil size were measured by OPD-Scan Ⅲ and Pentacam. Pairwise t-tests, Pearson tests, and Bland-Altman analyses were used, respectively, to assess the difference, correlation, and agreement between the devices. RESULTS: There was no significant difference in photopic chord kappa and corneal spherical aberration between the two instruments (P = 0.054, P = 0.065). Chord alpha and pupil size varied significantly between the two instruments (P < 0.001). OPD-Scan III results revealed a significant association between photopic chord kappa and mesopic chord kappa (r = 0.823, P < 0.001). There was a significant positive correlation between photopic and mesopic chord kappa measured by OPD-Scan Ⅲ and chord kappa measured by Pentacam (r = 0.840, r  = 0.757, P < 0.001). The chord alpha evaluated by the two tools had a moderate correlation (r = 0.442, P < 0.001) between them. Bland-Altman analysis showed that there was excellent agreement between the two instruments in measuring chord kappa and corneal spherical aberration, while the chord alpha and pupil size were not consistent. CONCLUSIONS: The chord kappa and corneal spherical aberration measured by OPD-Scan III and Pentacam were consistent in the preoperative decision making of multifocal intraocular lens implantation in cataract patients, both of which have clinical guiding significance. In addition, OPD-Scan III provides more comprehensive day and night chord kappa and pupil diameters, which improves clinical advice for patients with complicated ocular diseases and high demands for nocturnal vision.

Seasonal variations of macrozoobenthic community trophic structure in the waters adjacent to the seaweed beds of Dalian Island in the North Yellow Sea.

To investigate the effects of algal detritus export on the trophic structure of macrozoobenthic community in the adjacent benthic habitat during the bloom and decline of macroalgae, we collected macrozoobenthos from the adjacent sea area of Dalian Island in the North Yellow Sea in May (the algal bloom period) and August (the algal decay period) of 2020. We quantifyied the seasonal changes in the trophic structure of macrozoobenthic community by using carbon and nitrogen stable isotope techniques. Results showed that δ13C and δ15N values of macrozoo-benthos in May ranged from -23.14‰ to -14.24‰, 6.21‰ to 12.90‰, respectively, and -22.36‰ to -14.13‰, 5.33‰ to 12.00‰, respectively in August. Results of PERMANOVA analysis showed that δ13C values of macrozoobenthos differed significantly between the two months, while δ15N values were not significantly different. Based on the Euclidean distance, the macrozoobenthic communities in both months could be classified into five trophic functional groups. The trophic levels of macrozoobenthos ranged from 2.00 (Nitidotellina minuta) to 3.97 (Glycera onomichiensis) in May and from 2.00 (N. minuta) to 3.96 (G. onomichiensis) in August. The δ13C range, δ15N range, mean centroid distance, total area and corrected standard ellipse areas which represented community trophic structure indices in August were higher than those in May. Our results indicated that the trophic diversity level and trophic niche width of the macrozoobenthic community in the adjacent sea area of the seaweed bed were higher in the algal decline season.

The Role of Post-Translational Modifications in Regulation of NLRP3 Inflammasome Activation.

Pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) induce NLRP3 inflammasome activation, and subsequent formation of active caspase-1 as well as the maturation of interleukin-1ß (IL-1ß) and gasdermin D (GSDMD), mediating the occurrence of pyroptosis and inflammation. Aberrant NLRP3 inflammasome activation causes a variety of diseases. Therefore, the NLRP3 inflammasome pathway is a target for prevention and treatment of relative diseases. Recent studies have suggested that NLRP3 inflammasome activity is closely associated with its post-translational modifications (PTMs). This review focuses on PTMs of the components of the NLRP3 inflammasome and the resultant effects on regulation of its activity to provide references for the exploration of the mechanisms by which the NLRP3 inflammasome is activated and controlled.

Effects of Schisandra chinensis Polysaccharide-Conjugated Selenium Nanoparticles on Intestinal Injury in Mice.

Schisandra chinensis polysaccharide (SCP) is an experimental therapeutic for the treatment of intestinal injury. Selenium nanoparticle modification can improve the bioactivity of polysaccharides. In this study, SCP was firstly extracted and purified by a DEAE-52 column, then SCP-Selenium nanoparticles (SCP-Se NPs) were prepared, and the procedure was optimized. Thereafter, the obtained SCP-Se NPs were characterized by transmission electron microscope, X-ray diffraction, energy-dispersive X-ray spectroscopy, and Fourier transform infrared spectroscopy. The influence of different storage environments on the stability of colloidal SCP-Se NPs was also investigated. Finally, the therapeutic effects of SCP-Se NPs on LPS-induced intestinal inflammatory injuries in mice were evaluated. Results showed that the optimized SCP-Se NPs were amorphous, uniform, spherical particles with a diameter of 121 nm, and the colloidal solution was stable at 4 °C for at least 14 d. Moreover, SCP-Se NPs could more effectively alleviate LPS-induced diarrhea, intestinal tissue injury, and tight junction destruction and decrease the elevated expression levels of TNF-α, IL-1ß, and IL-6 compared with SCP. These results demonstrate that SCP-Se NPs may alleviate LPS-induced enteritis through their anti-inflammatory effects, indicating that SCP-Se NPs can serve as a good candidate for preventing and treating enteritis in the livestock and poultry industry.

OAT3 Participates in Drug-Drug Interaction between Bentysrepinine and Entecavir through Interactions with M8-A Metabolite of Bentysrepinine-In Rats and Humans In Vitro.

Bentysrepinine (Y101) is a novel phenylalanine dipeptide for the treatment of hepatitis B virus. Renal excretion played an important role in the elimination of Y101 and its metabolites, M8 and M9, in healthy Chinese subjects, although the molecular mechanisms of renal excretion and potential drug-drug interactions (DDIs) remain unclear. The present study aimed to determine the organic anion transporters (OATs) involved in the renal disposition of Y101 and to predict the potential DDI between Y101 and entecavir, the first-line agent against HBV and a substrate of OAT1/3. Pharmacokinetic studies and uptake assays using rat kidney slices, as well as hOAT1/3-HEK293 cells, were performed to evaluate potential DDI. The co-administration of probenecid (an inhibitor of OATs) significantly increased the plasma concentrations and area under the plasma concentration-time curves of M8 and M9 but not Y101, while reduced renal clearance and the cumulative urinary excretion of M8 were observed in rats. The time course of Y101 and M8 uptake via rat kidney slices was temperature-dependent. Moreover, the uptake of M8 was inhibited significantly by probenecid and benzylpenicillin, but not by p-aminohippurate or tetraethyl ammonium. M8 was found to be a substrate of hOAT3, but Y101 is not a substrate of either hOAT1 or hOAT3. Additionally, the entecavir inhibited the uptake of M8 in the hOAT3-transfected cells and rat kidney slices in vitro. Interestingly, no significant changes were observed in the pharmacokinetic parameters of Y101, M8 or entecavir, regardless of intravenous or oral co-administration of Y101 and entecavir in rats. In conclusion, M8 is a substrate of OAT3 in rats and humans. Furthermore, M8 also mediates the DDI between Y101 and entecavir in vitro, mediated by OAT3. We speculate that it would be safe to use Y101 with entecavir in clinical practice. Our results provide useful information with which to predict the DDIs between Y101 and other drugs that act as substrates of OAT3.

Perceived Participation in Decision-Making on Primary Surgery and Associated Factors Among Early Breast Cancer Patients: A Cross-sectional Study.

BACKGROUND: Breast cancer patients wish to participate in the treatment decision-making, but the perceived participation was inconsistent with the willingness, leading to poor patient outcomes. OBJECTIVE: The aims of this study were to explore the perceived participation in the primary surgery decision-making among Chinese patients with early-stage breast cancer (BCa) and to analyze the relationships of demographic and clinical factors, participation competence, self-efficacy, social support, and doctors' promotion of participation with the guidance of the capability, opportunity, motivation-behavior system (the COM-B system). METHODS: Paper surveys were used to collect data from 218 participants. The participation competence, self-efficacy, social support, and the doctor facilitation of involvement were evaluated to measure factors related to perceived participation among early-stage BCa. RESULTS: Perceived participation was low, and participants with a high level of participation competence, self-efficacy, and social support and who were employed and had a higher education level and higher family income perceived higher participation in primary surgery decision-making. CONCLUSIONS: Perceived participation was low and may be facilitated by patients' internal and external factors during the decision-making process. Health professionals should be aware that patient participation in decision-making is a type of self-care health behavior, and targeted decision support interventions should be provided to facilitate participation. IMPLICATIONS FOR PRACTICE: Patient-perceived participation may be evaluated from the perspective of self-care management behaviors among BCa patients. Nurse practitioners should emphasize their important roles in providing information, patient education, and psychological support to better contribute to the course of the treatment decision-making process for BCa patients who faced primary surgery.

Effect of X-ray radiation on the pharmacokinetics of apatinib in vivo in rats.

Purpose: The "radiotherapy-pharmacokinetic" ("RT-PK") phenomenon refers to the fact that radiation can significantly alter the pharmacokinetic behavior of a drug. At present, it is not clear whether there is an "RT-PK" phenomenon that can affect apatinib during concurrent chemoradiotherapy. In this study, we used a rat irradiation model to study the effects of X-ray radiation on absorption, tissue distribution, and excretion of apatinib. Method: Healthy Sprague-Dawley (SD) rats were randomly divided into control and radiation groups. The radiation group was given an appropriate dose of abdominal X-ray radiation, while the control group was not given irradiation. After 24 h of recovery, both groups were given apatinib solution 45 mg/kg by gavage. A quantitative LC-MS/MS method was developed to determine the concentration of apatinib in the rats, so as to compare the differences between the control and radiation groups and thus investigate the modulating effect of radiation on the pharmacokinetics of apatinib in rats. Results: After abdominal X-ray irradiation, the area under the curve (AUC0-t) of apatinib in rat plasma decreased by 33.8% and 76.3% at 0.5 and 2 Gy, respectively. Clearance (CL) and volume of distribution (Vd) increased and were positively correlated with radiation dose. X-ray radiation significantly reduced the concentration of apatinib in the liver and small intestine, and there was no tissue accumulation. In excretion studies, we found that X-ray radiation reduced the cumulative excretion of apatinib in feces and urine by 11.24% and 86.17%, respectively. Conclusion: Abdominal X-ray radiation decreased plasma exposure, tissue distribution, and excretion of apatinib in rats, suggesting that the RT-PK phenomenon affects apatinib. We speculate that this RT-PK phenomenon is closely related to changes in metabolic enzymes in vivo. In clinical practice, when apatinib is combined with radiotherapy, attention should be paid to adjusting the dose of apatinib and optimizing the treatment plan to alleviate the adverse effects of this RT-PK phenomenon.

Evaluation of JUN, FN1 and LAMB1 polymorphisms in pterygium in a Chinese Han population.

PURPOSE: To explore the underlying molecular mechanism of pterygium and identify the key genes regulating the development of pterygium. METHODS: Differentially expressed mRNAs were obtained from the Gene Expression Omnibus (GEO) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID (http://david.abcc.ncifcrf.gov/). The differential expressions of hub genes were verified using the reverse transcription-real-time fluorescent quantitative PCR (RT-qPCR). The function of the hub genes was further confirmed based on associations between the single nucleotide polymorphisms (SNPs) in hub genes and pterygium. The genotyping results were analyzed using SNPStats online software in five gene models, including codominant, dominant, recessive, overdominant, and log-additive. Five gene models were analyzed using SNPStats. RESULTS: We found that 240 genes were significantly differentially expressed. Functional enrichment analysis showed that focal adhesion pathway is extremely meaningful, among which JUN, FN1, and LAMB1 were verified to significantly differentially express in pterygium (P = 0.0011, P = 0.0018, and P = 0.0050, respectively). However, the all nine candidate SNPs (rs11688, rs3748814 in JUN; rs1263, rs1132741, rs1250259 in FN1; rs20556, rs35710474, rs25659, rs4320486 in LAMB1), were not statistically associated with pterygium. CONCLUSION: Our results demonstrated that JUN, FN1, and LAMB1 polymorphisms were not associated with susceptibility to pterygium in Chinese Han population. Considering the fact that these three genes are differentially expressed in pterygium, further research is needed to explain its involvement in pterygium.

[Identification of chemical constituents in Zhachong Shisanwei Pills by UPLC-Q-TOF-MS/MS].

Zhachong Shisanwei Pills, composed of 13 Chinese medicinal materials, are used for treating the diseases such as hemiplegia, pain of muscles and bones, rheumatism, and joint pain. The chemical composition and pharmacodynamics of Zhachong Shisanwei Pills have not been reported. Ultra-performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to quickly identify the chemical components of Zhachong Shisanwei Pills, which was performed with Shim-pack GIST C_(18) column(4.6 mm×150 mm, 5 µm). The gradient elution was conducted with methanol-0.05% acetic acid as the mobile phase. Electrospray ionization mass spectrometry(ESI-MS) was carried out in both positive and negative ion modes. The compounds were identidied based on accurate relative molecular weight, fragment ion species, and the MS data of reference substances and in literature. In conclusion, a total of 98 compounds were identified, including 19 organic acids, 36 flavonoids, 13 volatile oils, 8 tannins, 5 2-(2-phenylethyl)chromones, 5 amino acids, 3 sesquiterpenoids, 3 alkaloids, and 2 other compounds. This study characte-rized the chemical components of Zhachong Shisanwei Pills rapidly for the first time, laying a foundation for further research on the pharmacodynamic material basis and quality evaluation.

Assembled graph neural network using graph transformer with edges for protein model quality assessment.

Acquainting protein's structure is of vital importance to accurately understanding its function. Computational method of deep learning has made great progress in protein structure prediction from sequence, and has the potential to help structural biology research. The computational methods usually require independent protein structure model quality assessment to select the best from the model pool or guide protein structure refinement. We construct a graph neural network finely assembled with Graph Transformer Feature Extractor and message-passing layers for protein model quality assessment. The graph based method can more naturally embody the protein structure than a sequence or voxelized representation method. Although the widely used graph convolutional network has a strong ability to learn spatial patterns, it does not weigh the dependencies of different nodes on other nodes. So we introduce Graph Transformer to excavate the different degrees of neighboring residue nodes contributing to their local environments and extract local features. This is subsequently followed by message-passing layers to transmit-receive local information. Our network makes better use of edge information and is lightweight since relatively few input features and number of network layers, and experimental results demonstrate that our model outperforms various existing methods. Core code is made freely available at: https://github.com/Crystal-Dsq/proteinqa.

Tricarboxylate Citrate Transporter of an Oleaginous Fungus Mucor circinelloides WJ11: From Function to Structure and Role in Lipid Production.

The citrate transporter protein (CTP) plays an important role in citrate efflux from the mitochondrial matrix to cytosol that has great importance in oleaginous fungi. The cytoplasmic citrate produced after citrate efflux serves as the primary carbon source for the triacylglycerol and cholesterol biosynthetic pathways. Because of the CTP's importance, our laboratory has extensively studied its structure/function relationships in Mucor circinelloides to comprehend its molecular mechanism. In the present study, the tricarboxylate citrate transporter (Tct) of M. circinelloides WJ11 has been cloned, overexpressed, purified, kinetically, and structurally characterized. The Tct protein of WJ11 was expressed in Escherichia coli, isolated, and functionally reconstituted in a liposomal system for kinetic studies. Our results showed that Tct has a high affinity for citrate with Km 0.018 mM. Furthermore, the tct overexpression and knockout plasmids were created and transformed into M. circinelloides WJ11. The mitochondria of the tct-overexpressing transformant of M. circinelloides WJ11 showed a 49% increase in citrate efflux, whereas the mitochondria of the tct-knockout transformant showed a 39% decrease in citrate efflux compared to the mitochondria of wild-type WJ11. To elucidate the structure-function relationship of this biologically important transporter a 3D model of the mitochondrial Tct protein was constructed using homology modeling. The overall structure of the protein is V-shaped and its 3D structure is dimeric. The transport stability of the structure was also assessed by molecular dynamics simulation studies. The activity domain was identified to form hydrogen bond and stacking interaction with citrate and malate upon docking. Tricarboxylate citrate transporter has shown high binding energy of -4.87 kcal/mol to citric acid, while -3.80 kcal/mol to malic acid. This is the first report of unraveling the structural characteristics of WJ11 mitochondrial Tct protein and understanding the approach of the transporting toward its substrate. In conclusion, the present findings support our efforts to combine functional and structural data to better understand the Tct of M. circinelloides at the molecular level and its role in lipid accumulation.

Investigation of the metabolites of five major constituents from Berberis amurensis in normal and pseudo germ-free rats.

Berberis amurensis (Berberidaceae) is a traditional Chinese medicine, which is often used to treat hypertension, inflammation, dysentery and enteritis. It contains alkaloids, mainly including berberine, berbamine, magnoflorine, jatrorrhizine and palmatine. Berberis amurensis extracts (BAEs) is often orally taken. Oral herbs might be metabolized by intestinal bacteria in the small intestine. However, the interaction between the herb and the gut microbiota is still unknown. In the current study, UPLC/Q-TOF-MS/MS combined with Metabolitepilot and Peakview software was used to identify the metabolites of BAEs in anti-biotic cocktail induced pseudo germ-free rats and normal rats. As a result, a total of 46 metabolites in normal rats were detected and its main metabolic pathways include demethylation, dehydrogenation, methylation, hydroxylation, sulfation and glucuronidation. Only 29 metabolites existed in pseudo germ-free rats. Dehydrogenated metabolites (M29, M30, M34 and M36), methylated metabolites (M33, M41 and M46) and other metabolites were not detected in pseudo germ-free rats. The result implied that the intestinal bacteria have an influence on the metabolism of BAEs. Furthermore, this investigation might contribute to the understanding of the metabolism of BAEs, and further promote its clinical application.

Molecular Mechanism of Citrate Efflux by the Mitochondrial Citrate Transporter CT in Filamentous Fungus Mucor circinelloides WJ11.

The mitochondrial citrate transporter (MCT) plays an important role in citrate efflux from the mitochondria in eukaryotes, and hence provides a direct correlation between carbohydrate metabolism and lipid synthesis. Our previous studies on transporters confirmed the presence of two MCTs (TCT and CT) in oleaginous Mucor circinelloides WJ11 associated with high lipid accumulation. However, the molecular mechanism of citrate efflux from the mitochondria by MCT in M. circinelloides is still unclear. To study the citrate transport mechanism of CT, the citrate transporter gene was expressed in Escherichia coli, and its product was purified. The citrate transport activity of the protein was studied in CT reconstituted liposomes. Our results showed high efficiency of CT for [14C] citrate/citrate exchange with K m 0.01 mM at 25°C. Besides citrate, other molecules such as oxaloacetate, malate, fumarate, succinate aconitate, oxoadipate, isocitrate, and glutamate also promote citrate transport. In addition, the ct overexpression and knockout plasmids were constructed and transferred into M. circinelloides WJ11, and the mitochondria were isolated, and the transport activity was studied. Our findings showed that in the presence of 10 mM malate, the mitochondria of ct-overexpressing transformant showed 51% increase in the efflux rate of [14C] citrate, whereas the mitochondria of the ct-knockout transformant showed 18% decrease in citrate efflux compared to the mitochondria of wild-type WJ11. This study provided the first mechanistic evidence of citrate efflux from the mitochondria by citrate transporter in oleaginous filamentous fungus M. circinelloides, which is associated with high lipid accumulation.

The Work Experience of Newly Recruited Male Nurses during COVID-19: A Qualitative Study.

PURPOSE: This study was to investigate the work experience of newly recruited male nurses during the COVID-19 pandemic. METHODS: With a phenomenological approach, this qualitative study was adopted semistructured interviews by phone or video calls. A total of 9 male nurses newly recruited for the COVID-19 wards in Chinese hospitals were interviewed for this study. And Colaizzi's method was applied for evaluation in the data analysis. RESULTS: Based on our findings, three themes were extracted. First, the newly recruited male nurses showed negative emotions at the beginning of COVID-19 epidemic, which was caused by changes in working conditions and content, but also prompted the nurses to change the way of coping with the crisis. Second, they gradually mastered the working skills and psychological training to cope with COVID-19 and developed a positive attitude toward life and a high sense of professional responsibility. Finally, we learned about their needs to respond to public health emergencies such as the COVID-19 pandemic. CONCLUSION: COVID-19 is a disaster for all of humanity. The newly recruited male nurses are an important force in emergency rescue. Although they suffered from short-term negative emotions, they quickly adapted to the crisis. In order to better prepare for future emergencies, the disaster response capacity of newly recruited male nurses needs to be further improved. In addition, newly recruited male nurses have a strong demand for timely and personalized career development guidance.

Self-efficacy, psychological distress, and marital quality in young and middle-aged couples facing lymphoma: The mediating effect of dyadic coping.

OBJECTIVE: This study explored the mediating role of dyadic coping between self-efficacy, psychological distress and marital quality among young and middle-aged couples facing lymphoma. METHODS: A total of 243 couples in which the patients were lymphoma were recruited to complete Dyadic Coping Inventory, Locke-Wallace Marital Adjustment Scale for both. And Strategies Used by People to Promote Health, Fear of Progression Questionnaire-Short Form for patients; General Self-Efficacy Scale and Hospital Anxiety and Depression Scale for spouses. We used the statistical programs SPSS 20.0 and SPSS Amos 20.0 for data analysis. RESULTS: There were significant correlations between patient-spouse's dyadic coping and marriage quality scores. The patients' dyadic coping scores were significantly associated with their self-efficacy, fear of cancer recurrence scores, marriage quality, their spouse's self-efficacy, and marriage quality. The spouses' dyadic coping scores were significantly associated with their self-efficacy, anxiety, and marriage quality. The actor-partner interdependence mediation model analysis mediator effect of dyadic coping in the relationship between self-efficacy, psychological distress, and marriage quality had a good fit, with χ2 /df = 17.106, p = 0.194; root mean square error of approximation = 0.036; GFI = 0.992; CN = 243. CONCLUSIONS: For both patient and spouses, dyadic coping mediated impact of self-efficacy on marriage quality of themselves and their spouses, and individuals' dyadic coping mediated impact their psychological distress on marriage quality of themselves and spouses. The study highlighted the need for couple-based interventions and including strategies combined with individual and dyadic therapy for both partners.

Surgery decision conflict and its related factors among newly diagnosed early breast cancer patients in China: A cross-sectional study.

AIM: The aim of this study was to explore surgery decision conflict and its related factors among newly diagnosed early breast cancer patients in China. DESIGN: A cross-sectional survey study was conducted. METHODS: A total of 262 patients confronted with surgery decision-making were enrolled. The related factors were assessed with a demographic questionnaire, the Chinese version of the Decision Conflict Scale (DCS-C-16) and the Patient Participation Competence Scale (PPCS). RESULTS: Patients had a high level of decision conflict that was negatively correlated with the PPCS score. Age, marital status, living environment, education level, family income, cancer stage and the PPCS score were independent factors influencing decision conflict. Marital status, education level, cancer stage and participation competence were significant predictors of decision conflict. Patients who had higher participation competence were married, were well educated and had a lower cancer stage were likely to experience lower decision conflict.