Revealing the Role of the Ionomer at the Triple-Phase Boundary in a Proton-Exchange Membrane Water Electrolyzer.

In the anodic catalyst layer of a proton-exchange membrane (PEM) water electrolyzer, the triple-phase boundary (TPB) is mainly distributed on the surface of ultrafine iridium-based catalysts encapsulated by the ionomer within the catalyst-ionomer agglomerate. It is found that the ionomer at the TPB acts as a barrier to mass transport and a buffer for the bubble coverage during the oxygen evolution reaction (OER). The barrier effect can decrease the OER performance of the catalysts inside the agglomerate by ≤23%, while the buffer effect can separate the bubble evolution sites from the OER sites, turning the instant deactivation caused by the bubble coverage into a gradual performance loss caused by local water starvation. However, this local water starvation still deteriorates the catalyst performance because of the affinity of the ionomer surface for bubbles. Introducing additional transport paths into the agglomerate can reduce the barrier effect and regulate the bubble behavior, reducing the overpotential by 0.308 V at 5 A cm-2.

Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion.

BACKGROUND: For the first time, we investigated the oncological role of plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7 (TEM7), in hepatocellular carcinoma (HCC). AIM: To investigate the oncological profile of PLXDC1 in HCC. METHODS: Based on The Cancer Genome Atlas database, we analyzed the expression of PLXDC1 in HCC. Using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, we validated our results. The prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features, such as patient survival, methylation level, tumor immune microenvironment features, and immune cell surface checkpoint expression. Finally, to assess the immune evasion potential of PLXDC1 in HCC, we used the tumor immune dysfunction and exclusion (TIDE) website and immunohistochemical staining assays. RESULTS: Based on immunohistochemistry, qRT-PCR, and Western blot assays, overexpression of PLXDC1 in HCC was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and PLXDC1-related risk scores were also associated with a poor prognosis. CONCLUSION: As a result of this study analyzing PLXDC1 from multiple biological perspectives, it was revealed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial.

Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) present a promising alternative, capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders. This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP. The research design included administering UC-MSCs at escalating doses of 0.5 × 106 cells/kg, 1.0 × 106 cells/kg, and 2.0 × 106 cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase, followed by a dose of 2.0 × 106 cells/kg weekly for the dose-expansion phase. Adverse events, platelet counts, and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period. Ultimately, 12 (with an addition of three patients in the 2.0 × 106 cells/kg group due to dose-limiting toxicity) and six patients were enrolled in the dose-escalation and dose-expansion phase, respectively. Thirteen patients (13/18, 72.2%) experienced one or more treatment emergent adverse events. Serious adverse events occurred in four patients (4/18, 22.2%), including gastrointestinal hemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). The response rates were 41.7% in the dose-escalation phase (5/12, two received 1.0 × 106 cells/kg per week, and three received 2.0 × 106 cells/kg per week) and 50.0% (3/6) in the dose-expansion phase. The overall response rate was 44.4% (8/18) among all enrolled patients. To sum up, UC-MSCs are effective and well tolerated in treating refractory ITP (ClinicalTrials.gov ID: NCT04014166).

Knowledge, attitudes, and practices regarding cancer screening and primary prevention among ethnic minorities in mainland China: A literature review.

Objective: Cancer screening and primary prevention are effective strategies for addressing the burden of cancer. However, cancer health disparity exists in accessing cancer screening services among ethnic minorities in mainland China. Exploring knowledge, attitudes, and practices regarding cancer screening and primary prevention is an effective way to understand minority groups' participation in these activities and the barriers to their participation. However, no review has summarized the relevant evidence. This study explored the evidence on cancer screening and primary prevention among ethnic minorities in mainland China, including their knowledge (knowledge level and awareness rate), attitudes (positive/negative attitudes, beliefs, and perceptions), and practices (uptake and participation rate). Methods: Five online databases (MEDLINE, EMBASE, PubMed, China National Knowledge Infrastructure [CNKI], and Wanfang Data) were searched to identify literature. Data on knowledge, attitudes, and practices regarding cancer screening and primary prevention among ethnic minority groups and the influential factors were extracted and summarized. Results: Twelve articles on studies with a total of 36,464 participants were included. Most of the studies focused only on breast and cervical cancer, women, and Uyghurs. The ethnic minority groups in the reviewed studies had a low level of knowledge about cancer screening and primary prevention and insufficient practices (cancer screening and primary prevention service uptake rate < 40.0%) but moderate to highly positive attitudes. Conclusions: This review revealed the insufficient knowledge and practices of cancer screening and primary prevention among ethnic minority groups in mainland China, whose members hold generally positive attitudes toward screening. More evidence pertaining to diverse ethnic minority groups and other cancer types is needed.

Metabolomics profile and machine learning prediction of treatment responses in immune thrombocytopenia: A prospective cohort study.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction and impaired platelet production. The mechanisms underlying ITP and biomarkers predicting the response of drug treatments are elusive. We performed a metabolomic profiling of bone marrow biopsy samples collected from ITP patients admission in a prospective study of the National Longitudinal Cohort of Hematological Diseases. Machine learning algorithms were conducted to discover novel biomarkers to predict ITP patient treatment responses. From the bone marrow biopsies of 91 ITP patients, we quantified a total of 4494 metabolites, including 1456 metabolites in the positive mode and 3038 metabolites in the negative mode. Metabolic patterns varied significantly between groups of newly diagnosed and chronic ITP, with a total of 876 differential metabolites involved in 181 unique metabolic pathways. Enrichment factors and p-values revealed the top metabolically enriched pathways to be sphingolipid metabolism, the sphingolipid signalling pathway, ubiquinone and other terpenoid-quinone biosynthesis, thiamine metabolism, tryptophan metabolism and cofactors biosynthesis, the phospholipase D signalling pathway and the phosphatidylinositol signalling system. Based on patient responses to five treatment options, we screened several metabolites using the Boruta algorithm and ranked their importance using the random forest algorithm. Lipids and their metabolism, including long-chain fatty acids, oxidized lipids, glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine biosynthesis, helped differentiate drug treatment responses. In conclusion, this study revealed metabolic alterations associated with ITP in bone marrow supernatants and a potential biomarker predicting the response to ITP.

Proteomics landscape and machine learning prediction of long-term response to splenectomy in primary immune thrombocytopenia.

This study aimed to identify key proteomic analytes correlated with response to splenectomy in primary immune thrombocytopenia (ITP). Thirty-four patients were retrospectively collected in the training cohort and 26 were prospectively enrolled as validation cohort. Bone marrow biopsy samples of all participants were collected prior to the splenectomy. A total of 12 modules of proteins were identified by weighted gene co-expression network analysis (WGCNA) method in the developed cohort. The tan module positively correlated with megakaryocyte counts before splenectomy (r = 0.38, p = 0.027), and time to peak platelet level after splenectomy (r = 0.47, p = 0.005). The blue module significantly correlated with response to splenectomy (r = 0.37, p = 0.0031). KEGG pathways analysis found that the PI3K-Akt signalling pathway was predominantly enriched in the tan module, while ribosomal and spliceosome pathways were enriched in the blue module. Machine learning algorithm identified the optimal combination of biomarkers from the blue module in the training cohort, and importantly, cofilin-1 (CFL1) was independently confirmed in the validation cohort. The C-index of CFL1 was >0.7 in both cohorts. Our results highlight the use of bone marrow proteomics analysis for deriving key analytes that predict the response to splenectomy, warranting further exploration of plasma proteomics in this patient population.

Mapping and identification of a reverse mutation of Rht2 that enhances plant height and thousand grain weight in an elite wheat mutant induced by spaceflight.

As climate change continues to negatively impact our farmlands, abiotic factors like salinity and drought stress increasingly threaten global food security. The development of elite germplasms with resistance to multiple abiotic stresses is essential for breeding climate-resilient wheat cultivars. In this study, we determined that the previously reported salt-tolerant st1 mutant, obtained via spaceflight mutagenesis, may also resist to drought stress at the seedling stage. Moreover, our field trial revealed that yield-related traits including plant height, 1000-grain weight, and spike number per plant were significantly increased in st1 compared to the wild type. An F2 population of 334 individuals derived from a cross between the wild type and st1 displayed a bimodal distribution indicating that st1 plant height is controlled by a single major gene. Our Bulked Segregant Analysis and exome capture sequencing indicate that this gene is located on chromosome 4D. Further genetic linkage and gene sequence analysis suggests that a reverse mutation of Rht2 is putatively responsible for plant height variation in st1. Our genotypic and phenotypic analysis of the F2 population and F3 lines indicate that this reverse mutation significantly increases plant height and thousand grain weight but slightly decreases spike number per plant. Together, these results supply helpful information for the utilization of Rht2 in wheat breeding and provide an important material for breeding environmentally resilient, high-yield wheat varieties.

Effects of immersive virtual reality for alleviating anxiety, nausea and vomiting among patients with paediatric cancer receiving their first chemotherapy: protocol for a randomised controlled trial.

INTRODUCTION: Anxiety, nausea and vomiting are common side effects suffered by paediatric patients receiving chemotherapy. Emerging evidence supports the efficacy of immersive virtual reality (IVR) on improving anxiety and distress symptoms including nausea and vomiting in this vulnerable group. This trial aims to evaluate the effects of IVR intervention on anxiety, chemotherapy-induced nausea and vomiting and anticipatory nausea and vomiting in patients with paediatric cancer receiving first chemotherapy. METHOD AND ANALYSIS: An assessor-blinded, randomised controlled trial with a mixed methods evaluation approach. On the basis of our pilot results, 128 chemotherapy-naive patients with paediatric cancer scheduled to receive their first intravenous chemotherapy will be recruited from a public hospital and randomly allocated to intervention (n=64) or control groups (n=64). The intervention group will receive the IVR intervention for three sessions: 2 hours before the first chemotherapy, 5 min before and during their first chemotherapy and 5 min before and during their second chemotherapy, respectively. The control group will receive standard care only. A subsample of 30 participants in the intervention group will be invited for a qualitative interview. Study instruments are: (1) short form of the Chinese version of the State Anxiety Scale for Children, (2) visual analogue scale for anticipatory nausea and vomiting, (3) Chinese version of the Multinational Association of Supportive Care in Cancer Antiemesis Tool and (4) individual face-to-face semistructured interviews to explore intervention participants' perceptions of the IVR intervention. ETHICS AND DISSEMINATION: This study has been approved by the Hong Kong Children's Hospital Research Ethics Committee (HKCH-REC-2021-009). The findings will be disseminated in peer-reviewed journals and through local or interventional conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2100048732.

Unraveling the Effects of Carbon Corrosion on Oxygen Transport Resistance in Low Pt Loading Proton Exchange Membrane Fuel Cells.

Cost and durability have become crucial hurdles for the commercialization of proton exchange membrane fuel cells (PEMFCs). Although a continuous reduction of Pt loading within the cathode catalyst layers (CCLs) can lead to cost savings, it also increases the oxygen transport resistance, which is further compounded by key material degradation. Hence, a further understanding of the mechanism of significant performance loss due to oxygen transport limitations at the triple phase boundaries (TPBs) during the degradation process is critical to the development of low Pt loading PEMFCs. The present study systematically investigates the impact of carbon corrosion in CCLs on the performance and oxygen transport process of low Pt loading PEMFCs through accelerated stress tests (ASTs) that simulate start-up/shutdown cycling. A decline in peak power density from 484.3 to 251.6 mW cm-2 after 1500 AST cycles demonstrates an apparent performance loss, especially at high current densities. The bulk and local oxygen transport resistances (rbulk and Rlocal) of the pristine cell and after 200, 600, 1000, and 1500 AST cycles are quantified by combining the limiting current method with a dual-layer CCL design. The results show that rbulk increased from 1527 to 1679 s cm-2, Rlocal increased from 0.38 to 0.99 s cm-1, and the local oxygen transport resistance with the normalized Pt surface area (rlocal) exhibited an increase from 18.5 to 32.0 s cm-1, indicating a crucial impact on the structure collapse and changes in the chemical properties of the carbon supports in the CCLs. Further, the interaction between the ionomer and carbon supports during the carbon corrosion process is deeply studied via electrochemical quartz crystal microbalance and molecular dynamics simulations. It is concluded that the oxygen-containing functional groups on the carbon surface could impede the adsorption of ionomers on carbon supports by creating an excessively water-rich layer, which in turn aggravates the formation of ionomer agglomerations within the CCLs. This process ultimately leads to the destruction of the TPBs and hinders the transport of oxygen through the ionomer.

Fatigue and health-related quality of life in patients with immune thrombocytopenia: a longitudinal assessment in China.

BACKGROUND: There is lacking studies of longitudinally assessment of fatigue and health-related quality of life (HRQoL) among Chinese immune thrombocytopenia (ITP) adults. We aimed to evaluate changes in fatigue and HRQoL and identify the associated factors. METHODS: Patients' characteristics, Functional Assessment of Chronic Illness Therapy (FACIT-F) and the ITP-specific Patient Assessment Questionnaire (ITP-PAQ) scores at admission (T0), at discharge (T1), and three months after discharge (T2) were collected. Linear mixed effects models were used to examine changes over time. RESULTS: We included 175 patients. The mean score of FACIT-F at T0 was 37.2 and increased at T1 (39.0), while then decreased at T2 (34.7). Patients who were single, retired, had persistent ITP, splenomegaly had more severe fatigue, whereas those who had not received any prior treatment and had a bleeding score of 0 at admission had milder fatigue. The mean score of ITP-PAQ was 57.7 at T0, then gradually increased to 60.3 at T1 and 62.8 at T2. Patients with persistent ITP and those who have never received treatment for ITP have better HRQoL. CONCLUSION: ITP adults' fatigue and HRQoL were impaired. Patients' fatigue improved at discharge but worsened at three months after discharge, while HRQoL gradually improved over time.

Establishment and application of three predictive models of anastomotic leakage after rectal cancer sphincter-preserving surgery.

BACKGROUND: Anastomotic leakage (AL) occurs frequently after sphincter-preserving surgery for rectal cancer and has a significant mortality rate. There are many factors that influence the incidence of AL, and each patient's unique circumstances add to this diversity. The early identification and prediction of AL after sphincter-preserving surgery are of great significance for the application of clinically targeted preventive measures. Developing an AL predictive model coincides with the aim of personalised healthcare, enhances clinical management techniques, and advances the medical industry along a more precise and intelligent path. AIM: To develop nomogram, decision tree, and random forest prediction models for AL following sphincter-preserving surgery for rectal cancer and to evaluate the predictive efficacy of the three models. METHODS: The clinical information of 497 patients with rectal cancer who underwent sphincter-preserving surgery at Jincheng People's Hospital of Shanxi Province between January 2017 and September 2022 was analyzed in this study. Patients were divided into two groups: AL and no AL. Using univariate and multivariate analyses, we identified factors influencing postoperative AL. These factors were used to establish nomogram, decision tree, and random forest models. The sensitivity, specificity, recall, accuracy, and area under the receiver operating characteristic curve (AUC) were compared between the three models. RESULTS: AL occurred in 10.26% of the 497 patients with rectal cancer. The nomogram model had an AUC of 0.922, sensitivity of 0.745, specificity of 0.966, accuracy of 0.936, recall of 0.987, and accuracy of 0.946. The above indices in the decision tree model were 0.919, 0.833, 0.862, 0.951, 0.994, and 0.955, respectively and in the random forest model were 1.000, 1.000, 1.000, 0.951, 0.994, and 0.955, respectively. The DeLong test revealed that the AUC value of the decision-tree model was lower than that of the random forest model (P < 0.05). CONCLUSION: The random forest model may be used to identify patients at high risk of AL after sphincter-preserving surgery for rectal cancer owing to its strong predictive effect and stability.

Virtual Reality-Based Intervention to Reduce Preoperative Anxiety in Adults Undergoing Elective Surgery: A Randomized Clinical Trial.

IMPORTANCE: Preoperative anxiety is common among adult patients undergoing elective surgery and is associated with negative outcomes. Virtual reality (VR)-based interventions have been considered simpler, safer, and more effective for reducing anxiety in patients undergoing surgery than conventional care. OBJECTIVE: To examine the effectiveness of a VR-based intervention with preoperative education in reducing preoperative anxiety among adult patients undergoing elective surgery. DESIGN, SETTING, AND PARTICIPANTS: An assessor-blinded prospective randomized clinical trial was conducted to recruit adult patients aged 18 years or older who were scheduled for their first elective surgery procedure under general anesthesia within the next 2 to 4 weeks at a preanesthesia assessment clinic in Hong Kong from July to December 2022. INTERVENTIONS: Participants were randomly assigned to either an intervention group (an 8-minute immersive 360° VR video tour in the operating theater via a head-mounted display console) or a control group (standard care). MAIN OUTCOMES AND MEASURES: The primary outcome of preoperative anxiety was measured using the Amsterdam Preoperative Anxiety and Information Scale (range, 6-30; higher scores indicate greater anxiety), and the secondary outcomes (ie, stress, preparedness, and pain) were assessed by Visual Analog Scale at 3 time points: baseline at beginning of clinical session (T0), at the end of the clinical session immediately after the intervention (T1), and before the surgery (T2). Pain, satisfaction levels, and postoperative length of stay were evaluated after the surgery (T3). Simulation sickness was assessed after the intervention by use of the Simulation Sickness Questionnaire. A generalized estimating equations model was applied to compare changes in outcomes over time. RESULTS: A total of 74 participants (mean [SD] age, 46.34 [14.52] years; 38 men [51.4%] and 36 women [48.6%]) were recruited and randomized to the control group (37 participants) and intervention group (37 participants). Compared with the control group, the VR-based intervention group showed significantly decreased preoperative anxiety at T1 (ß, -5.46; 95% CI, -7.60 to -3.32; P < .001) and T2 (ß, -5.57; 95% CI, -7.73 to -3.41; P < .001), lower stress at T1 (ß, -10.68; 95% CI, -16.00 to -5.36; P < .001) and T2 (ß, -5.16; 95% CI, -9.87 to -0.45; P = .03), and higher preparedness at T1 (ß, 6.60; 95% CI, 0.97 to 12.19; P = .02). Satisfaction levels were significantly increased in the intervention group vs the control group (mean [SD] score, 81.35 [9.24] vs 65.28 [8.16]; difference, 16.07; 95% CI, 12.00 to 20.15; P < .001). No significant differences in pain and postoperative length of stay were found. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that a VR-based intervention is a feasible and effective way to reduce preoperative anxiety in adult patients undergoing elective surgery. Given the promising results of this study, further study in the form of large-scale, multicenter, randomized clinical trials with broader implementation is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100051690.

Nursing students' perceived anxiety and heart rate variability in mock skill competency assessment.

BACKGROUND: Skill competency assessments induce stress and anxiety and may affect nursing student performance. Little is known about stress and perceived anxiety levels and their relationship in the mock skill competency assessment. METHODS: A cross-sectional study was conducted to examine the stress levels (as assessed by heart rate variability, HRV) and perceived anxiety before, during and after the mock skill competency assessment, and to explore their relationships to performance in a total of ninety first-year undergraduate nursing students. RESULTS: The HRV decreased significantly during the assessment and increased significantly 10 min after the assessment (p < 0.01). Higher performers showed significantly lower HRV during and after the assessment (p < 0.01). The assessment score was negatively correlated with HRV during and after the assessment (p < 0.05). CONCLUSIONS: Considering assessment-related stress and anxiety through a mock assessment prior to the actual skill assessment provides implications for future nursing education.

Endoplasmic Reticulum Stress in Systemic Lupus Erythematosus and Lupus Nephritis: Potential Therapeutic Target.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Approximately one-third to two-thirds of the patients with SLE progress to lupus nephritis (LN). The pathogenesis of SLE and LN has not yet been fully elucidated, and effective treatment for both conditions is lacking. The endoplasmic reticulum (ER) is the largest intracellular organelle and is a site of protein synthesis, lipid metabolism, and calcium storage. Under stress, the function of ER is disrupted, and the accumulation of unfolded or misfolded proteins occurs in ER, resulting in an ER stress (ERS) response. ERS is involved in the dysfunction of B cells, macrophages, T cells, dendritic cells, neutrophils, and other immune cells, causing immune system disorders, such as SLE. In addition, ERS is also involved in renal resident cell injury and contributes to the progression of LN. The molecular chaperones, autophagy, and proteasome degradation pathways inhibit ERS and restore ER homeostasis to improve the dysfunction of immune cells and renal resident cell injury. This may be a therapeutic strategy for SLE and LN. In this review, we summarize advances in this field.