The relationship between self-efficacy and error orientation of nursing students during clinical internships: a cross-sectional study.

Background: Nursing students often make clinical errors due to their limited clinical experience and their orientation toward errors, revealing their attitude and behavioral tendencies regarding nursing errors. Understanding how self-efficacy, motivation, and a sense of security influence the error orientation of nursing students is important for developing strategies to enhance their error orientation. Objectives: This study aimed to explore the relationship between self-efficacy, motivation, and error orientation of nursing students during clinical internships. Method: This was a cross-sectional study. An electronic questionnaire was distributed to nursing students from 14 September 2023 to 30 September at a comprehensive tertiary A teaching hospital in Zhengzhou, Henan province. The instruments used in this study included the General Information Questionnaire, General Self-efficacy Scale, Achievement Motives Scale, Security Scale, and Error Orientation Scale. Statistical Product and Service Software Automatically (SPSSAU) was used to perform statistical description, mediation analysis, and moderated mediation analyses. Results: A total of 510 nursing students were included in this study. The motivation for success and failure-escaping fully mediated the relationships between self-efficacy and error orientation of nursing students, with a mediation effect of 0.101 (95% CI: 0.058-0.144). The security of nursing students moderated both the direct effect of this model and the indirect effect of motivation for failure-escaping. When security was high, the self-efficacy of nursing students was positively correlated with their error orientation, with an effect of 0.059 (95% CI: 0.003~0.116). When security was high, the moderation effect was significant, with an effect of -0.012 (95% CI: -0.026~-0.002). However, at low and median levels of security, the mediation effect was non-existent. Conclusion: The motivation for success and failure escaping play different roles in the paths between self-efficacy and error orientation. Clinical nursing teachers should take measures to enhance the motivation for success but reduce the failure-escaping motivation to improve the error orientation of nursing students. Additionally, it is crucial to pay attention to and improve the sense of security of students during clinical internships.

First report of cucumber green mottle mosaic virus infecting Cynanchum rostellatum in China.

Cucumber green mottle mosaic virus (CGMMV) was first discovered on cucumber in the United Kingdom in 1935 (Ainsworth, 1935), and has spread worldwide except to Antarctica (Jones, 2021). Given its extensive damage, it is considered an important pathogen on global cucurbit plants and fruit crops. In China, CGMMV was first reported on pumpkin in Guangxi Province in 2003 (Qin et al., 2005), and occurred on 34 plants species across 23 provinces (Liu et al., 2016). Cynanchum rostellatum is a member of the family Apocynaceae. In July 2021, leaves of C. rostellatum exhibiting virus-like symptoms (yellowing, severe crinkling, deformation) were observed and collected in Liaoning Province, China. Aphids were also observed on the leaves and stems (Fig. S1) of the plants and were collected. Total RNA was extracted from diseased leaves following the CTAB method, followed by the depletion of ribosomal RNAs (rRNA) with TIANSeq rRNA Depletion Kit (Tiangen, China). The RNAs were, then processed into a DNBSEQ LncRNA-Seq library, and sequenced on the MGISEQ-2000 platform at BGI Genomics (Wuhan, China). A total of 106.98 M clean reads were obtained after data filtering using SOAPnuke software (BGI, China). The clean reads were assembled into contigs using CLC Genomics Workbench 11 (Qiagen, USA) and Trinity v2.0.6 (Haas et al., 2013). A contig (4,760 reads, average coverage:73.76) of 6,391 nucleotides was found to share the highest sequence identity (99.83%) with CGMMV isolate GDLZ (MK933286), irrespective of other virus-like contigs related to Polerovirus and Totivirus. Based on the genome of GDLZ isolate, seven specific primers (Table S1) were designed to amplify the full viral genomic sequences using a PrimeScriptTM One-Step RT-PCR Kit. Seven expected amplicons were obtained, cloned, and sequenced. The complete genome was determined to be 6,423 nucleotides (GenBank accession number OR854819) in length and designated as LNMJ isolate. LNMJ shared 96.8%-99.7% nucleotide sequence identities with CGMMV isolates from China. Phylogenetic analysis based on the complete genome sequences showed that LNMJ clustered together with CGMMV isolates hn (GenBank accession number KC851866), GDLZ (GenBank accession number MK933286), and JD8 (GenBank accession number KM873784) from China. The specific primers LM-TJ-3F/3R were designed to determine the virus-symptom association for LNMJ, and all twelve symptomatic C. rostellatum plants collected from fields tested positive for LNMJ. Two out of six randomly selected aphids from the diseased plants also tested positive. To further prove its infectivity, LNMJ was inoculated mechanically onto ten healthy Nicotiana benthamiana plants, and the results indicated a high infection rate of 80% (8/10), at 30 days post-inoculation despite no distinct symptoms observed. To our knowledge, this is the first report of the natural infection of C. rostellatum plants with CGMMV. C. rostellatum is a widespread herb in China (Wei et al., 2019) and more surveys are needed to determine the distribution of CGMMV. The habitats of C. rostellatum span diverse agroecological zones, and thus our study underscores the potential spillover of CGMMV to neighboring crops as a significant risk.

Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors.

The overall cancer incidence and death toll have been increasing worldwide. However, the conventional therapies have some obvious limitations, such as non-specific targeting, systemic toxic effects, especially the multidrug resistance (MDR) of tumors, in which, autophagy plays a vital role. Therefore, there is an urgent need for new treatments to reduce adverse reactions, improve the treatment efficacy and expand their therapeutic indications more effectively and accurately. Combination therapy based on autophagy regulators is a very feasible and important method to overcome tumor resistance and sensitize anti-tumor drugs. However, the less improved efficacy, more systemic toxicity and other problems limit its clinical application. Nanotechnology provides a good way to overcome this limitation. Co-delivery of autophagy regulators combined with anti-tumor drugs through nanoplatforms provides a good therapeutic strategy for the treatment of tumors, especially drug-resistant tumors. Notably, the nanomaterials with autophagy regulatory properties have broad therapeutic prospects as carrier platforms, especially in adjuvant therapy. However, further research is still necessary to overcome the difficulties such as the safety, biocompatibility, and side effects of nanomedicine. In addition, clinical research is also indispensable to confirm its application in tumor treatment.

Preclinical multi-physiologic monitoring of immediate-early responses to diverse treatment strategies in breast cancer by optoacoustic imaging.

Optoacoustic imaging enables the measurement of tissue oxygen saturation (sO2) and blood perfusion while being utilized for detecting tumor microenvironments. Our aim was to employ multispectral optoacoustic tomography (MSOT) to assess immediate-early changes of hemoglobin level and sO2 within breast tumors during diverse treatments. Mouse breast cancer models were allocated into four groups: control, everolimus (EVE), paclitaxel (PTX), and photodynamic therapy (PDT). Hemoglobin was quantified daily, as well as sO2 and blood perfusion were verified by immunohistochemical (IHC) staining. MSOT showed a temporal window of enhanced oxygenation and improved perfusion in EVE and PTX groups, while sO2 consistently remained below baseline in PDT. The same results were obtained for the IHC. Therefore, MSOT can monitor tumor hypoxia and indirectly reflect blood perfusion in a non-invasive and non-labeled way, which has the potential to monitor breast cancer progression early and enable individualized treatment in clinical practice.

A Bioorthogonal Antidote Against the Photosensitivity after Photodynamic Therapy.

As an effective and non-invasive treatment modality for cancer, photodynamic therapy (PDT) has attracted considerable interest. With the recent advances in the photosensitizing agents, the fiber-optic systems, and other aspects, its application is extended to a wide range of superficial and localized cancers. However, for the few clinically used photosensitizers, most of them suffer from the drawback of causing prolonged photosensitivity after the treatment. As a result, post-PDT management is also a crucial issue. Herein, a facile bioorthogonal approach is reported that can effectively suppress this common side effect of PDT in nude mice. It involves the use of an antidote that contains a black-hole quencher BHQ-3 conjugated with a bicyclo[6.1.0]non-4-yne (BCN) moiety and a tetrazine-substituted boron dipyrromethene-based photosensitizer. By using tumor-bearing nude mice as an animal model, it is demonstrated that after PDT with this photosensitizer, the administration of the antidote can effectively quench the photodynamic activity of the residual photosensitizer by bringing the BHQ-3 quencher close to the photosensitizing unit through a rapid click reaction. It results in substantial reduction in skin damage upon light irradiation. The overall results demonstrate that this simple and facile strategy can provide an effective means for minimizing the photosensitivity after PDT.

The Large Molecular Weight Polysaccharide from Wild Cordyceps and Its Antitumor Activity on H22 Tumor-Bearing Mice.

Cordyceps has anti-cancer effects; however, the bioactive substance and its effect are still unclear. Polysaccharides extracted from Cordyceps sinensis, the fugus of Cordyceps, have been reported to have anti-cancer properties. Thus, we speculated that polysaccharides might be the key anti-tumor active ingredients of Cordyceps because of their larger molecular weight than that of polysaccharides in Cordyceps sinensis. In this study, we aimed to investigate the effects of wild Cordyceps polysaccharides on H22 liver cancer and the underlying mechanism. The structural characteristics of the polysaccharides of WCP were analyzed by high-performance liquid chromatography, high-performance gel-permeation chromatography, Fourier transform infrared spectrophotometry, and scanning electron microscopy. Additionally, H22 tumor-bearing BALB/c mice were used to explore the anti-tumor effect of WCP (100 and 300 mg/kg/d). The mechanism by WCP inhibited H22 tumors was uncovered by the TUNEL assay, flow cytometry, hematoxylin-eosin staining, quantitative reverse transcription-polymerase chain reaction, and Western blotting. Here, our results showed that WCP presented high purity with an average molecular weight of 2.1 × 106 Da and 2.19 × 104 Da. WCP was determined to be composed of mannose, glucose, and galactose. Notably, WCP could inhibit the proliferation of H22 tumors not only by improving immune function, but also by promoting the apoptosis of tumor cells, likely through the IL-10/STAT3/Bcl2 and Cyto-c/Caspase8/3 signaling pathways, in H22 tumor-bearing mice. Particularly, WCP had essentially no side effects compared to 5-FU, a common drug used in the treatment of liver cancer. In conclusion, WCP could be a potential anti-tumor product with strong regulatory effects in H22 liver cancer.

Polysaccharides extracted from mulberry fruits (Morus nigra L.): antioxidant effect of ameliorating H2O2-induced liver injury in HepG2 cells.

BACKGROUND: Mori Fructus is an economical and readily available traditional Chinese medicine and food. Polysaccharides in Mori Fructus have clear antioxidant activity and have been found to alleviate oxidative stress (OS)-induced liver damage in experimental studies. The mechanism of regulation of cellular antioxidant activity by mulberry polysaccharides has been suggested to be Nrf2, but it is not clear whether the Nrf2 pathway is mediated by activation of other targets, and the exact process of effects in hepatocytes has yet to be elucidated. METHODS: In this study, the basic characterization of total polysaccharides extracted from mulberry fruits (Morus nigra Linn.) was analyzed. A model of oxidative damage induced by H2O2 in HepG2 cells was established. The levels of cellular oxidation-related markers, including ROS, SOD and Gpx, were then examined. Furthermore, Q-PCR and Western-blot were used to detect the expression of genes and proteins related to the PI3K/Akt-mediated Nrf2 signaling pathway. RESULTS: The results showed that a total mulberry polysaccharides (TMP) has a molecular weight of 57.5 kDa with a pyranose ring mainly composed of glucose (48.81%), galactose (22.79%) and mannose (18.2%). TMP reduced the accumulation of ROS in HepG2 cells after H2O2 treatment and modulated the activity of SOD and Gpx. Q-PCR and Western-blot showed that TMP could up-regulate the expression of p-PI3K, p-AKT, Nrf2, NQO1 and HO-1. CONCLUSIONS: This study demonstrates that TMP can reduce ROS accumulation in H2O2-treated HepG2 cells and restore cell viability by activating the PI3K/AKT-mediated Nrf2 pathway. TMP may be a potent antioxidant agent that could slow down oxidative damage to the liver.

Enzyme-Responsive Double-Locked Photodynamic Molecular Beacon for Targeted Photodynamic Anticancer Therapy.

An advanced photodynamic molecular beacon (PMB) was designed and synthesized, in which a distyryl boron dipyrromethene (DSBDP)-based photosensitizer and a Black Hole Quencher 3 moiety were connected via two peptide segments containing the sequences PLGVR and GFLG, respectively, of a cyclic peptide. These two short peptide sequences are well-known substrates of matrix metalloproteinase-2 (MMP-2) and cathepsin B, respectively, both of which are overexpressed in a wide range of cancer cells either extracellularly (for MMP-2) or intracellularly (for cathepsin B). Owing to the efficient Förster resonance energy transfer between the two components, this PMB was fully quenched in the native form. Only upon interaction with both MMP-2 and cathepsin B, either in a buffer solution or in cancer cells, both of the segments were cleaved specifically, and the two components could be completely separated, thereby restoring the photodynamic activities of the DSBDP moiety. This PMB could also be activated in tumors, and it effectively suppressed the tumor growth in A549 tumor-bearing nude mice upon laser irradiation without causing notable side effects. In particular, it did not cause skin photosensitivity, which is a very common side effect of photodynamic therapy (PDT) using conventional "always-on" photosensitizers. The overall results showed that this "double-locked" PMB functioned as a biological AND logic gate that could only be unlocked by the coexistence of two tumor-associated enzymes, which could greatly enhance the tumor specificity in PDT.

Non-Esterified Fatty Acid-Induced Apoptosis in Bovine Granulosa Cells via ROS-Activated PI3K/AKT/FoxO1 Pathway.

Non-esterified fatty acid (NEFA), one of negative energy balance (NEB)'s most well-known products, has a significant impact on cows' reproductive potential. Our study used an in vitro model to investigate the deleterious effects of NEFA on bovine granulosa cells (BGCs) and its underlying molecular mechanism. The results showed that high levels of NEFA led to the accumulation of reactive oxygen species (ROS), increased the expression of apoptosis-related factors such as Bcl2-Associated X/B-cell lymphoma-2 (Bax/Bcl-2) and Caspase-3, and down-regulated steroid synthesis-related genes such as sterol regulatory element binding protein 1 (SREBP-1), cytochrome P450c17 (CYP17), and cytochrome P450 aromatase (CYP19), to promote oxidative stress, cell apoptosis, and steroid hormone synthesis disorders in BGCs. In addition, NEFA significantly inhibited phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-AKT) activity and increased forkhead box O1 (FoxO1) expression. To further explore the role of the PI3K/AKT/FoxO1 signaling pathway in NEFA, we found that pretreatment with AKT-specific activator SC79 (5 mg/mL) for 2 h or transfection with FoxO1 knockdown siRNA in BGCs could alleviate the negative effects of NEFA treatment by decreasing Bax/Bcl-2 ratio and Caspase-3 expression, and upregulating SREBP-1, CYP17, and CYP19 expression. Meanwhile, SC79 significantly inhibited NEFA-induced dephosphorylation and massive nuclear translocation of FoxO1. Taken together, the NEFA induced oxidative stress, apoptosis, and steroid hormone synthesis disorders in BGCs by inhibiting the PI3K/AKT pathway that regulates FoxO1 phosphorylation and nuclear translocation. Our findings help to clarify the molecular mechanisms underlying the negative effects of high levels of NEFA on BGCs.

Nursing adherence, barriers and facilitators to conduct post-stroke dysphagia screening and assessment: A study based on theoretical domain framework.

BACKGROUND: There are an increasing number of evidence-based recommendations for managing dysphagia in post-stroke patients. However, it is unclear whether nurses adopt these recommendations in their daily nursing practices. AIMS: This study aimed to explore nurses' adherence, barriers, facilitators and views on dysphagia screening and assessment of post-stroke dysphagia. METHODS: In this study, multiple methods were adopted. In Phase 1, a general information questionnaire and a knowledge-attitude-practice and barriers/facilitators questionnaire for dysphagia screening and assessment were distributed in 55 hospitals online. In Phase 2, semi-structured interviews were conducted to explore nurses' views on barriers. Descriptive and one-way variance analyses were used to analyse the quantitative data, while content analysis was used to analyse the qualitative data. This study adheres to STROBE and COREQ guidelines. RESULTS: Nine hundred and forty-two completed questionnaires were collected. Only 36.52% of the nurses screened for swallow function in patients as a guideline. The biggest barrier was 'memory, attention and decision process', with an average score of 3.22 (.74). The different stages of implementation had various types and degrees of barriers (p < .001). Five themes were extracted after interviews, namely 'Inadequate environment and resource support', 'Increased workload', 'Professional value perception', 'Organisational culture', and 'Poor knowledge and skill'. CONCLUSIONS: Nurses' practice of dysphagia screening and assessment of patients with dysphagia after stroke were inadequate, and the barriers originated from patients, leadership and the nurses themselves. RELEVANCE TO CLINICAL PRACTICE: This research extracted five barriers of guidance adherence for post-stroke dysphagia screening and assessment and identified the different kinds and degrees of barriers in five implementation stages, providing a basis for nursing managers to break through the bottleneck of guideline implementation. PATIENT OR PUBLIC CONTRIBUTION: The nurses recruited in this study completed validated questionnaires in the survey and suggestive answers in interviews.

Guidance Value of Procalcitonin Detection in Selecting Switching Points for Sequential Therapy in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease Complicated by Respiratory Failure.

Objective: To analyse the guiding value of procalcitonin (PCT) for the selection of ventilation switching points in sequential mechanical ventilation for patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and respiratory failure, and to provide a reference for the optimisation of mechanical ventilation for patients with COPD and respiratory failure. Methods: The study included 160 patients with an acute exacerbation of COPD complicated by respiratory failure who received sequential mechanical ventilation treatment. They were divided into two groups of 80 participants. The critical point of the pulmonary infection observation window (PIC) was used as the switching point for sequential mechanical ventilation treatment in the control group, and PCT clinical node was used as the switching point for sequential mechanical ventilation treatment in the observation group. The invasive ventilation time, non-invasive mechanical ventilation time, total mechanical ventilation time, intensive care unit (ICU) treatment time, complication rate and prognosis were compared for the two groups. Results: (1) There was no significant difference in the respiratory rate, heart rate, arterial systolic pressure, arterial oxygen partial pressure, arterial carbon dioxide partial pressure or pH value between the two groups after 1 day of treatment, and (2) invasive mechanical ventilation time, non-invasive mechanical ventilation time, total mechanical ventilation time, ICU treatment time and the incidence of complications were significantly different in the two groups (P = 0.0001). Conclusion: Detecting PCT can guide the selection of ventilation switching points in sequential mechanical ventilation therapy for patients with COPD with respiratory failure in the acute exacerbation stage, effectively reduce the misevaluation of PIC switching points so that patients can obtain stable criteria for judgement and effectively improve the efficiency and safety of mechanical ventilation treatment for patients in the acute exacerbation stage.

HSP90AA1 promotes viability and lactate production but inhibits hormone secretion of porcine immature Sertoli cells.

Heat shock protein 90 (HSP90), as a molecular chaperone, regulates hundreds of protein clients under both physiological and stress conditions in eukaryotic cells. However, the functional role of HSP90 in mammalian male reproduction remains largely unknown. Here, we aimed to investigate the function and effect of HSP90AA1 on the basic and reproductive function of pig immature Sertoli cells (iSCs). We first confirmed that the transfection of pBI-CMV3-HSP90AA1 vector into porcine iSCs for 24 h significantly increased mRNA and protein levels of HSP90AA. Moreover, HSP90AA1 over-expression significantly increased cell viability and the PLK2 mRNA abundance, promoted lactate production via elevating the LDHA activity, and inhibited the secretion of anti-Mullerian hormone and estradiol. In comparison, HSP90AA inhibition by allylamino-17-demethoxygeldanamycin (17-AAG) (2 µM) treatment of pig iSCs for 36 h had a totally contrasting effect, i.e. significantly reduced cell viability, promoted cell apoptosis via modulating expression of genes related to cell cycle and apoptosis (CCNB1, CCN1, PLK2, PTMA, YBX3 and CASP3), suppressed lactate production via dropping LDHA activity, but increased the secretion of anti-Mullerian hormone and estradiol. Taken together, our findings demonstrated that HSP90AA1 could regulate positively cell viability and lactate production, but negatively the secretion of reproductive hormones (anti-Mullerian hormone and estradiol). However, the detailed molecular mechanism of HSP90AA1 remains to be investigated.

Multifunctional Nanosnowflakes for T1-T2 Double-Contrast Enhanced MRI and PAI Guided Oxygen Self-Supplementing Effective Anti-Tumor Therapy.

Introduction: Accurate tumor diagnosis is essential to achieve the ideal therapeutic effect. However, it is difficult to accurately diagnose cancer using a single imaging method because of the technical limitations. Multimodal imaging plays an increasingly important role in tumor treatment. Photodynamic therapy (PDT) has received widespread attention in tumor treatment due to its high specificity and controllable photocytotoxicity. Nevertheless, PDT is susceptible to tumor microenvironment (TME) hypoxia, which greatly reduces the therapeutic effect of tumor treatment. Methods: In this study, a novel multifunctional nano-snowflake probe (USPIO@MnO2@Ce6, UMC) for oxygen-enhanced photodynamic therapy was developed. We have fabricated the honeycomb-like MnO2 to co-load chlorin e6 (Ce6, a photosensitizer) and ultrasmall superparamagnetic iron oxide (USPIO, T1-T2 double contrast agent). Under the high H2O2 level of tumor cells, UMC efficiently degraded and triggered the exposure of photosensitizers to the generated oxygen, accelerating the production of reactive oxygen species (ROS) during PDT. Moreover, the resulting USPIO and Mn2+ allow for MR T1-T2 imaging and transformable PAI for multimodal imaging-guided tumor therapy. Results: TEM and UV-vis spectroscopy results showed that nano-snowflake probe (UMC) was successfully synthesized, and the degradation of UMC was due to the pH/ H2O2 responsive properties. In vitro results indicated good uptake of UMC in 4T-1 cells, with maximal accumulation at 4 h. In vitro and in vivo experimental results showed their imaging capability for both T1-T2 MR and PA imaging, providing the potential for multimodal imaging-guided tumor therapy. Compared to the free Ce6, UMC exhibited enhanced treatment efficiency due to the production of O2 with the assistance of 660 nm laser irradiation. In vivo experiments confirmed that UMC achieved oxygenated PDT under MR/PA imaging guidance in tumor-bearing mice and significantly inhibited tumor growth in tumor-bearing mice, exhibiting good biocompatibility and minimal side effects. Conclusion: The multimodal imaging contrast agent (UMC) not only can be used for MR and PA imaging but also has oxygen-enhanced PDT capabilities. These results suggest that UMC may have a good potential for further clinical application in the future.

Nitrogen Disturbance Awakening the Intrinsic Activity of Nickel Phosphide for Boosted Hydrogen Evolution Reaction.

Invited for this month's cover is the group of Qingfeng Sun at the Zhejiang A&F University. The image shows that the N-doped Ni2 P exhibits excellent electrocatalytic activity for hydrogen evolution reaction (HER). The Research Article itself is available at 10.1002/cssc.202200072.

Nitrogen Disturbance Awakening the Intrinsic Activity of Nickel Phosphide for Boosted Hydrogen Evolution Reaction.

Nickel phosphide (Ni2 P) has emerged as a promising candidate to substitute Pt-based catalysts for hydrogen evolution reaction (HER) due to the hydrogenase-like catalytic mechanism and concomitantly low cost. However, its catalytic activity is still not comparable to that of noble-metal-based catalysts, and innovative strategies are still urgently needed to further improve its performance. Herein, a self-supported N-doped Ni2 P on Ni foam (N-Ni2 P/NF) was rationally designed and fabricated through a facile NH4 H2 PO2 -assisted gas-solid reaction process. As an HER catalyst in alkaline medium, the obtained N-Ni2 P/NF revealed excellent electrocatalytic performance with a distinctly low overpotential of 50 mV at 10 mA cm-2 , a small Tafel slope of 45 mV dec-1 , and long-term stability for 25 h. In addition, the spectroscopic characterizations and density functional theory calculations confirmed that the incorporation of N regulated the original electronic structure of Ni2 P, enhanced its intrinsic catalytic property, optimized the Gibbs free energy of reaction intermediates, and ultimately promoted the HER process. This work provides an atomic-level insight into the electronic structure modulation of metal phosphides and opens an avenue for developing advanced transition metal phosphides-based catalysts.

Identification of Preoperative Serum Metabolites Associated With Postoperative Opioid Consumption in Gastric Cancer Patients by Extreme Phenotype Sampling.

BACKGROUND: Postoperative pain increases patients' risk and opioids remain the main analgesics to relieve it. However, improper use of opioids causes many side effects and identification of suitable preoperative biomarkers that predict postoperative opioid consumption may aid clinicians in improving analgesic strategies for patients. The activity of metabolites modulates multiple phenotypes and can function as biomarkers for disease prediction and diagnosis. OBJECTIVES: In this study, we explore whether preoperative serum metabolites are associated with postoperative opioid consumption in gastric cancer patients by extreme phenotype sampling. STUDY DESIGN: This was a case-control, observational study. SETTING: This study was conducted at Beijing Cancer Hospital. METHODS: One hundred and sixty-nine gastric cancer patients participated in this study. After exclusion of 51 patients, postoperative pain intensity and opioid consumption data of 118 patients were collected. Patients were sorted by gender and classified into 2 groups based on opioid consumption during the 24h postoperative period. Patients in the sufentanil high consumption (SHC) group and patients in the sufentanil low consumption (SLC) group were ranked in the top or bottom 30% of sufentanil consumption, respectively. Untargeted metabolomic analysis of preoperative serum samples from both groups was performed by ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and orthogonal partial least square discriminant analysis. Allele frequencies of DAO rs10156191 and MAOB rs1799836 SNPs in both groups were detected by Sanger sequencing. RESULTS: Thirty-five metabolites in preoperative serum were significantly different between the SLC and SHC groups. Hydrogen phosphate had the highest area under the curve in a ROC analysis (0.98), suggesting that it may serve as a predictive biomarker for postoperative opioid consumption. Differential metabolites unique to the male and female subgroups were also identified. Histidine metabolism was the most altered pathway between the SLC and SHC groups. There were no significant differences in the allele frequencies of 2 SNPs associated with histamine degradation; however, 2 metabolites of histamine degradation, imidazole-4-acetaldehyde, and methylimidazole acetaldehyde, showed different trends in the 2 groups. LIMITATIONS: Our study was restricted to gastric cancer patients with strict exclusion criteria, which may limit the generalizability to other groups. CONCLUSION: Preoperative serum metabolites were associated with postoperative opioid consumption. Different efficiencies of histamine degradation may be one cause of the variable sensitivity of patients to acute pain and warrants further study.

Site-Specific Displacement-Driven Activation of Supramolecular Photosensitizing Nanoassemblies for Antitumoral Photodynamic Therapy.

The delivery and activation of photosensitizers in a specific manner is crucial in photodynamic therapy. For an antitumoral application, it can confine the photodynamic action on the cancer cells, thereby enhancing the treatment efficacy and reducing the side effects. We report herein a novel supramolecular photosensitizing nanosystem that can be specifically activated in cancer cells and tumors that overexpress epidermal growth factor receptor (EGFR). It involves the self-assembly of the amphiphilic host-guest complex of a ß-cyclodextrin-conjugated phthalocyanine-based photosensitizer (Pc-CD) and a ferrocene-substituted poly(ethylene glycol) (Mn = 2000) (Fc-PEG) in aqueous media. The resulting nanosystem Pc-CD@Fc-PEG with a hydrodynamic diameter of 124-147 nm could not emit fluorescence and generate reactive oxygen species due to the self-quenching effect and the ferrocene-based quencher. Upon interactions with molecules of adamantane substituted with an EGFR-targeting peptide (Ad-QRH*) in water and in EGFR-positive HT29 and A431 cells, the ferrocene guest species were displaced, resulting in disassembly of the nanoparticles and restoration of these photoactivities. The half-maximal inhibitory concentration values were down to 1.24 µM (for HT29 cells). The nanosystem Pc-CD@Fc-PEG could also be activated in an Ad-QRH*-treated HT29 tumor in nude mice, leading to increased intratumoral fluorescence intensity and effective eradication of the tumor upon laser irradiation. The results showed that this two-step supramolecular approach can actualize site-specific photosensitization and minimize nonspecific phototoxicity in a general photodynamic treatment.

Developing Smart Nanoparticles Responsive to the Tumor Micro-Environment for Enhanced Synergism of Thermo-Chemotherapy With PA/MR Bimodal Imaging.

With the development of nanotechnology, a theranostics nanoplatform can have broad applications in multimodal image-guided combination treatment in cancer precision medicine. To overcome the limitations of a single diagnostic imaging mode and a single chemotherapeutic approach, we intend to combat tumor growth and provide therapeutic interventions by integrating multimodal imaging capabilities and effective combination therapies on an advanced platform. So, we have constructed IO@MnO2@DOX (IMD) hybrid nanoparticles composed of superparamagnetic iron oxide (IO), manganese dioxide (MnO2), and doxorubicin (DOX). The nano-platform could achieve efficient T2-T1 magnetic resonance (MR) imaging, switchable photoacoustic (PA) imaging, and tumor microenvironment (TME)-responsive DOX release and achieve enhanced synergism of magnetic hyperthermia and chemotherapy with PA/MR bimodal imaging. The results show that IMD has excellent heating properties when exposed to an alternating magnetic field (AMF). Therefore, it can be used as an inducer for tumor synergism therapy with chemotherapy and hyperthermia. In the TME, the IMD nanoparticle was degraded, accompanied by DOX release. Moreover, in vivo experimental results show that the smart nanoparticles had excellent T2-T1 MR and PA imaging capabilities and an excellent synergistic effect of magnetic hyperthermia and chemotherapy. IMD nanoparticles could significantly inhibit tumor growth in tumor-bearing mice with negligible side effects. In conclusion, smart IMD nanoparticles have the potential for tumor diagnosis and growth inhibition as integrated diagnostic nanoprobes.

Melatonin mitigates Chloroquine-induced defects in porcine immature Sertoli cells.

Chloroquine (CQ) could function as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway, and is widely used on malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear. Here we showed that CQ could reduce iSC viability in a dose-dependent manner. CQ treatment (20 µM) on iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis, which could be partially rescued by melatonin (MT) (10 nM). Transcriptome profiling identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20 µM CQ vs. DMSO), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, only 467 (224 up- and 243 down-regulated) DEGs (CQ + MT vs. DMSO) could be found after MT (10 nM) addition, enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction pathways. Therefore, the partial rescue effects of MT on CQ treatment were confirmed by multiple assays (cell viability, ROS level, mitochondrial function, apoptosis, and mRNA levels of selected genes). Collectively, CQ treatment could impair porcine iSC viability by deranging the signaling pathways related to apoptosis and autophagy, which could be partially rescued by MT supplementation.

Gossypol exposure induces mitochondrial dysfunction and oxidative stress during mouse oocyte in vitro maturation.

Gossypol is a yellow natural polyphenolic compound extracted from the seeds, leaves, stems, and flower buds of the cotton plant. Several studies have shown that exposure to gossypol impacts reproductive health in both humans and animals. However, whether gossypol exposure would influence oocyte quality has not yet been determined. Here, we studied the effects of gossypol on the meiotic maturation of mouse oocytes in vitro. The results revealed that gossypol exposure did not affect germinal vesicle breakdown (GVBD) but significantly reduced polar body extrusion (PBE) rates. Moreover, we observed meiotic spindle organization and chromosome alignment were entirely disturbed after gossypol exposure. Further, gossypol exposure also caused mitochondrial dysfunction and abruptly decreased the levels of cellular ATP, and diminished the mitochondrial membrane potential (MMP). Accordingly, gossypol-induced oxidative stress was confirmed through an increased level of reactive oxygen species (ROS). Early apoptosis incidence also increased as identified by positive Annexin-V signaling. Collectively, the above findings provide evidence that gossypol exposure impaired oocyte meiotic maturation, disturbed spindle structure and chromosome dynamics, disrupted mitochondrial function, induced oxidative stress, and triggered early apoptosis. These findings emphasize gossypol's adverse effects on oocyte maturation and thus on female fertility.