Discrepancies in ASPECTS obtained by artificial intelligence and experts: Associated factors and prognostic implications.

PURPOSE: The differences between the Alberta Stroke Program Early CT Score (ASPECTS) obtained by experts and artificial intelligence (AI) software require elucidation. We aimed to characterize the discrepancies between the ASPECTS obtained by AI and experts and determine the associated factors and prognostic implications. METHODS: This multicenter, retrospective, observational cohort study included patients showing acute ischemic stroke caused by large-vessel occlusion in the anterior circulation. ASPECTS was determined by AI software (RAPID ASPECTS) and experts from the core laboratory. Interclass correlation coefficients (ICCs) and Bland-Altman plots were used to illustrate the consistency and discrepancies; logistic regression analyses were used to assess the correlates of inconsistency; and receiver operating characteristic analyses were performed to assess the diagnostic performance for predicting unfavorable clinical outcomes. RESULTS: The study population included 491 patients. The ICC for the expert and AI ASPECTS was 0.63 (95 % confidence interval [CI]: 0.25-0.79).The mean difference between expert and AI ASPECTS was 2.24. Chronic infarcts (odds ratio [OR], 1.9; 95 % CI, 1.1-3.4; P=0.021) and expert scores in the internal capsule (OR, 2.9; 95 % CI, 1.1-7.7; P=0.034) and lentiform (OR, 2.4; 95 % CI, 1.3-4.7; P=0.008) were significant correlates of inconsistency. The ASPECTS obtained by AI showed a significantly higher area under the curve for unfavorable outcomes (0.68 vs. 0.63, P=0.04). CONCLUSIONS: In comparison with expert ASPECTS, AI ASPECTS overestimated the infarct extent. Future studies should aim to determine whether AI ASPECTS assessments should use a lower threshold to screen patients for endovascular therapy.

Single-cell sequencing combined with spatial transcriptomics reveals that the IRF7 gene in M1 macrophages inhibits the occurrence of pancreatic cancer by regulating lipid metabolism-related mechanisms.

AIM: The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1-type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. METHODS: By utilising single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co-culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage-derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage-derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage-derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation-associated proteins in tumour tissues was examined using immunohistochemistry. RESULTS: Through combined analysis of scRNA-seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis. CONCLUSION: Overexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage-derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future.

The incidence, clinical features and risk factors for postoperative retropharyngeal hematoma and related dyspnea following anterior cervical discectomy and fusion: a single-center study of 10615 patients.

BACKGROUND CONTEXT: Postoperative retropharyngeal hematoma (PRH) and related dyspnea are rare but life-threatening complications following anterior cervical discectomy and fusion (ACDF) that require urgent recognition and treatment. However, current knowledge of PRH after ACDF is limited. Meanwhile, whether the morphological features of upper airway are the risk factors of PRH remains unknown. PURPOSE: The study aimed to investigate the incidence, clinical features, and risk factors, especially the morphological features of upper airway, of PRH and related dyspnea following ACDF. STUDY DESIGN: A nested case‒control study. PATIENT SAMPLE: Consecutive patients who underwent ACDF at a single institute from January 2010 to December 2021 were retrospectively reviewed. OUTCOME MEASURES: The outcome measures included the incidence, clinical features, intervention, outcome and risk factors for PRH and related dyspnea. METHODS: All patients with PRH were classified into the hematoma group. For each PRH subject, 3 control subjects without PRH were randomly selected as the control group. The clinical features, interventions and outcomes of patients were described. Potential risk factors were evaluated, including demographics, comorbidities, surgical characteristics, coagulation function, blood loss, preoperative blood pressure, and the morphological features of upper airway [prevertebral soft tissue thickness (PVT) and location of transverse arytenoid muscle (TAM) and epiglottis]. Univariate tests and multivariable logistic regression analysis were used to determine the risk factors for PRH. Subgroup analysis was also conducted for PRH patients with and without dyspnea. RESULTS: Among the 10615 patients who underwent ACDF, 18 (0.17%) developed PRH. The median time from the index surgery to PRH formation was 8.5 hours (25 and 75 percentile: 4 hours to 24 hours). All the PRH patients initially presented with wound swelling. Twelve (0.11%) patients presented dyspnea due to PRH, 2 of whom received urgent intubation and 1 of whom received emergent tracheotomy. All patients underwent hematoma evacuation, and most of them presented with completely relieved symptoms after evacuation, except for 1 patient who died from ischemic hypoxic encephalopathy. A level between the epiglottis and the TAM (LET) greater than 2, ossification of posterior longitudinal ligament (OPLL) and higher diastolic blood pressure (DBP) before surgery were found to be risk factors for PRH formation. Subgroup analysis revealed that a smaller prevertebral soft tissue thickness at C5 was associated with the development of dyspnea. CONCLUSION: This study is the largest study to date focusing on the PRH and related dyspnea after ACDF. Our study showed that the incidences of PRH and related dyspnea after ACDF were 0.17% and 0.11%, respectively. The predominant symptoms of PRH were wound swelling and acute dyspnea. Most PRH cases occurred in the acute postoperative period. We demonstrated the risk factors for PRH to be (1) OPLL, (2) LET≥2 and (3) higher DBP before surgery and advocate paying increased attention to upper airway morphological features for identifying the risk of PRH after ACDF. With urgent recognition and timely intervention, severe clinical outcomes could be avoided.

Psychometric properties and measurement invariance of the Chinese version of the cognitive emotion regulation questionnaire-short in patients with cancer.

OBJECTIVE: The study aimed to evaluate the psychometric properties and measurement invariance (MI) of the Chinese version of the cognitive emotion regulation questionnaire-short (CERQ-short) in cancer patients. METHODS: This cross-sectional study included 505 cancer patients from mainland China. In addition to sociodemographic and clinical characteristics, the CERQ-short and the distress thermometer were included in the study measures. RESULTS: Item analysis indicated a promising result. And the results of CFA indicated that the CERQ-short demonstrated satisfactory factorial validity in cancer patients. Cronbach's alpha coefficients were between 0.663 and 0.910, while McDonald's omega coefficients were between 0.664 and 0.910. The CERQ-short had sufficient convergent, discriminant and concurrent validity among cancer patients. Lastly, MI supported that the CERQ-short demonstrated strong measurement equivalence across gender, residence and age. CONCLUSIONS: This study shows that the Chinese version of the CERQ-short has convincing psychometric properties and MI, which supports its use in cancer patients.

Comparison of vonoprazan bismuth-containing triple therapy with quadruple therapy in Helicobacter pylori-infected treatment-naive patients: a prospective multicenter randomized controlled trial.

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

The effectiveness of positive psychological interventions for patients with cancer: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To evaluate the effectiveness of positive psychological interventions on quality of life, positive psychological outcomes and negative psychological outcomes in patients with cancer. BACKGROUND: Patients with cancer often suffer from various psychological problems and have a poor quality of life. Positive psychological interventions have been increasingly applied to patients with cancer, but the results of these studies have not been synthesized. DESIGN: A systematic review and meta-analysis of randomized controlled trials according to PRISMA. METHODS: Six English databases and four Chinese databases were searched from the inception to December 2022. Two reviewers independently assessed the risk of bias using the Cochrane Risk of Bias tool. RevMan was used for meta-analysis. RESULTS: Twenty-nine randomized controlled trials examined the effects of positive psychological interventions including meaning therapy, dignity therapy, positive psychotherapy, mindfulness- based intervention, life review, expressive writing intervention, acceptance and commitment psychotherapy, attention and interpretation therapy, compassion training and spiritual therapy on patients with cancer. Positive psychological interventions significantly improved the quality of life, enhanced positive psychological outcomes including well-being, meaning of life, self-esteem, optimism, resilience and self-efficacy and alleviated negative psychological outcomes including depression, anxiety and hopelessness. However, the heterogeneity of some outcomes was rather high, due to the wide diversity of the interventions included. CONCLUSION: Positive psychological interventions have potentially positive effects on improving quality of life, enhancing positive psychological outcomes and alleviating negative psychological outcomes in patients with cancer. However, due to the heterogeneity and the lack of follow-up studies, more high-quality studies are needed to confirm the results of our review and to clarify the long-term effects of positive psychological interventions. RELEVANCE TO CLINICAL PRACTICE: As feasible psychological interventions, healthcare professionals can consider applying appropriate positive psychological interventions according to the condition of cancer patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The Neurocomputational Mechanism Underlying Decision-Making on Unfairness to Self and Others.

Fairness is a fundamental value in human societies, with individuals concerned about unfairness both to themselves and to others. Nevertheless, an enduring debate focuses on whether self-unfairness and other-unfairness elicit shared or distinct neuropsychological processes. To address this, we combined a three-person ultimatum game with computational modeling and advanced neuroimaging analysis techniques to unravel the behavioral, cognitive, and neural patterns underlying unfairness to self and others. Our behavioral and computational results reveal a heightened concern among participants for self-unfairness over other-unfairness. Moreover, self-unfairness consistently activates brain regions such as the anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex, spanning various spatial scales that encompass univariate activation, local multivariate patterns, and whole-brain multivariate patterns. These regions are well-established in their association with emotional and cognitive processes relevant to fairness-based decision-making. Conversely, other-unfairness primarily engages the middle occipital gyrus. Collectively, our findings robustly support distinct neurocomputational signatures between self-unfairness and other-unfairness.

PA200-Mediated Proteasomal Protein Degradation and Regulation of Cellular Senescence.

Cellular senescence is closely related to DNA damage, proteasome inactivity, histone loss, epigenetic alterations, and tumorigenesis. The mammalian proteasome activator PA200 (also referred to as PSME4) or its yeast ortholog Blm10 promotes the acetylation-dependent degradation of the core histones during transcription, DNA repair, and spermatogenesis. According to recent studies, PA200 plays an important role in senescence, probably because of its role in promoting the degradation of the core histones. Loss of PA200 or Blm10 is a major cause of the decrease in proteasome activity during senescence. In this paper, recent research progress on the association of PA200 with cellular senescence is summarized, and the potential of PA200 to serve as a therapeutic target in age-related diseases is discussed.

[A new sesquiterpene from Syringa oblata].

In this study, the chemical components of ethanol extract from the aromatic parts of Syringa oblata were systematically separated and purified by silica gel column chromatography, thin layer plate preparation and liquid phase preparation. Combined with ultraviolet analyzer(UV), infrared analyzer(IR), nuclear magnetic resonance analyzer(NMR), high resolution mass spectrometer(HR-ESI-MS), X-ray diffraction and other spectrum technology as well as literature physicochemical data comparison methods for structural identification, a total of 10 compounds were identified. They were identified as oblatanoid D(1),(-)-T-muurolol(2), oblatanoid E-G(3-5), 14-noreudesma-3-hydroxy-3-en-2,9-dione(6), 1-isopropyl-2,7-dimethylnaphthalene(7), isocoradiol(8), α-calacorene(9), cadin-4-en-1-ß-ol(10). Compound 1 is a new sesquiterpene compound that has not been reported, and the other 9 compounds are isolated from S. oblata for the first time. The compound 1 has a significant protective effect on the LPS-induced inflammatory injury model of RAW264.7 cells.

Effects of meaning therapy on spirituality, psychological health, and quality of life in patients with cancer: A systematic review and meta-analysis of randomized controlled trials.

Objective: This study aimed to systematically review studies of meaning therapy on patients with cancer and to evaluate its effectiveness on spiritual outcomes, psychological outcomes, and quality of life (QOL). Methods: A comprehensive literature search were performed in five international databases (PubMed, Embase, Web of Science, The Cochrane Library, and CINAHL) and four Chinese databases (CNKI, Wanfang Data, VIP, and CBM) from the inception to August 2023. The methodological quality of each included studies was evaluated by using the revised Cochrane risk-of-bias tool for randomized trials. The random-effects model or fixed-effects model was utilized for effect size analysis, and the standardized mean difference (SMD) or mean difference (MD) along with its corresponding 95% confidence interval (CI) was computed. Meta-analysis was conducted by using the RevMan software 5.4.1. Results: Eight randomized controlled trials with 1251 participants were included in this review. Meta-analyses revealed that meaning therapy can significantly improve the spiritual outcomes including meaning in life (SMD = -0.48; 95% CI = -0.89 to -0.07; P = 0.02), hopelessness (SMD = -0.30; 95% CI = -0.51 to -0.09; P = 0.005), self-esteem (MD = -2.74; 95% CI = -4.17 to -1.32; P = 0.0002) and spiritual well-being (MD = -3.32; 95% CI = -5.63 to -1.01; P = 0.005), psychological outcomes including anxiety (MD = -0.66; 95% CI = -1.30 to -0.01; P = 0.05), depression (SMD = -0.37; 95% CI = -0.55 to -0.20; P < 0.0001), psychological distress (SMD = -0.35; 95% CI = -0.70 to -0.01; P = 0.04) and desire for hastened death (MD = -0.76; 95% CI = -1.47 to -0.05; P = 0.04), and QOL (SMD = -0.29; 95% CI = -0.50 to -0.09; P = 0.006) in patients with cancer. Conclusions: Meaning therapy has positive effects on improving spirituality, psychological health, and QOL of patients with cancer. More high-quality randomized controlled trials with larger sample sizes are warranted to confirm the results of our review and to clarify the long-term effects of meaning therapy in the future. Systematic review registration: PROSPERO (No. CRD42021278286).

[Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills].

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

Genetically modified pigs: Emerging animal models for hereditary hearing loss.

Hereditary hearing loss (HHL), a genetic disorder that impairs auditory function, significantly affects quality of life and incurs substantial economic losses for society. To investigate the underlying causes of HHL and evaluate therapeutic outcomes, appropriate animal models are necessary. Pigs have been extensively used as valuable large animal models in biomedical research. In this review, we highlight the advantages of pig models in terms of ear anatomy, inner ear morphology, and electrophysiological characteristics, as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss. Additionally, we discuss the prospects, challenges, and recommendations regarding the use pig models in HHL research. Overall, this review provides insights and perspectives for future studies on HHL using porcine models.

Population-based screening for colorectal cancer in Wuhan, China.

Fecal DNA test has emerged as a non-invasive alternative for colorectal cancer (CRC) screening in average-risk population. However, there is currently insufficient evidence in China to demonstrate the effectiveness of population-based CRC screening using fecal DNA based test. Here, a large-scale real-world study for CRC screening was implemented in Wuhan, Hubei province, China. A total of 98,683 subjects aged between 45 and 60 years were screened by a fecal DNA test (ColoTect®) which detected methylation status of SDC2, ADHFE1, and PPP2R5C. Participants who tested positive were advised to receive diagnostic colonoscopy. 4449 (4.5%) subjects tested positive for fecal DNA test, and 3200 (71.9%) underwent colonoscopy. Among these, 2347 (73.3%) had abnormal colonoscopy findings, of which 1330 (56.7%) subjects received pathological diagnosis. Detection rates for CRC and advanced precancerous lesions were 1.3% and 2.3%, respectively. Detection rates for nonadvanced adenomas and polyps were 14.0% and 21.6%, respectively. 28.0% of all colonoscopies showed colorectal neoplasm but lack pathological diagnosis. 6.1% showed other abnormalities such as enteritis. In conclusion, preliminary real-world evidence suggested that fecal DNA tests had promising diagnostic yield in population-based CRC screening. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=192838, identifier ChiCTR2300070520.

Discovery of novel peptide-dehydroepiandrosterone hybrids inducing endoplasmic reticulum stress with effective in vitro and in vivo anti-melanoma activities.

Steroid hybrids have emerged as a type of advantageous compound as they could offer improved pharmacological and pharmaceutical properties. Here, we report a series of novel peptide-dehydroepiandrosterone hybrids, which would effectively induce endoplasmic reticulum stress (ERS) and lead to apoptosis with outstanding in vitro and in vivo anti-melanoma effects. The lead compound IId among various steroids conjugated with peptides and pyridines showed effective in vivo activity in B16 xenograft mice: in medium- and high-dose treatment groups (60 and 80 mg/kg), compound IId would significantly inhibit the growth of tumours by 98%-99% compared to the control group, with the highest survival rate as well. Further mechanism studies showed that compound IId would damage the endoplasmic reticulum and upregulate the ERS markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), which could further regulate caspase and Bcl-2 family proteins and lead to cell apoptosis. The compound IId was also proven to be effective in inhibiting B16 cell migration and invasion.

Identification, characterization and application of M16AT, a new organic solvent-tolerant (R)-enantio-selective type IV amine transaminase from Mycobacterium sp. ACS1612.

Biocatalysis has emerged as a powerful alternative to traditional chemical methods, especially for asymmetric synthesis. As biocatalysts usually exhibit excellent chemical, regio- and enantioselectivity, they facilitate and simplify many chemical processes for the production of a broad range of products. Here, a new biocatalyst called, R-selective amine transaminases (R-ATAs), was obtained from Mycobacterium sp. ACS1612 (M16AT) using in-silico prediction combined with a genome and protein database. A two-step simple purification process could yield a high concentration of pure enzyme, suggesting that industrial application would be inexpensive. Additionally, the newly identified and characterized R-ATAs displayed a broad substrate spectrum and strong tolerance to organic solvents. Moreover, the synthetic applicability of M16AT has been demonstrated by the asymmetric synthesis of (R)-fendiline from of (R)-1-phenylethan-1-amine.

Inhibition of HMGB1 improves experimental mice colitis by mediating NETs and macrophage polarization.

OBJECTIVE: Inflammatory bowel disease (IBD) is listed by the World Health Organization as one of the modern intractable diseases. High mobility histone box 1 (HMGB1), originally described as a non-histone nucleoprotein involved in transcriptional regulation, was later identified as a pro-inflammatory cytokine that may contribute to the pathogenesis of inflammatory diseases such as IBD. Neutrophil extracellular traps (NETs) play an important role in the pathophysiology of IBD The aim of this study was to investigate the role of HMGB1 in experimental colitis mice and its potential mechanisms of action. METHODS: We first constructed the experimental colitis mouse model. Intervention of mice by rhHMGB1 supplementation or HMGB1 inhibition. The pathological morphology of the colon was observed using HE staining. Apoptosis of colonic tissue intestinal epithelial cells was evaluated using Tunel assay. The expression of HMGB1, ZO-1 and occludin in colon tissue was detected by immunohistochemistry, ELISA and western-blot. We also assessed the effects of HMGB1 on colonic injury, NETs content, macrophage polarization and inflammatory cells in mice. The regulatory effect of HMGB1 inhibition on NETs was assessed by combining DNase I. RESULTS: Inhibition of HMGB1 significantly reduced the inflammatory model in experimental colitis mice, as evidenced by reduced body weight, increased colonic length, reduced DAI scores and apoptosis, reduced inflammatory response, and improved colonic histopathological morphology and intestinal mucosal barrier function. Meanwhile, inhibition of HMGB1 was able to reduce the expression of CD86, citH3 and MPO and increase the expression of CD206 in the colonic tissue of mice. In addition, DNase I intervention was also able to improve colonic inflammation in mice. And the best effect was observed when DNase I and inhibition of HMGB1 were intervened together. CONCLUSION: Inhibition of HMGB1 ameliorates IBD by mediating NETs and macrophage polarization.

Post-synthetic modified luminescent metal-organic framework for the detection of berberine hydrochloride in a traditional Chinese herb.

In this work, a novel fluorescence sensor UiO-66-PSM based on post-synthetic modified metal-organic frameworks was prepared for the detection of berberine hydrochloride (BBH) in the traditional Chinese herb Coptis. UiO-66-PSM was synthesized by a simple Schiff base reaction with UiO-66-NH2 and phthalaldehyde (PAD). The luminescence quenching can be attributed to the photo-induced electron transfer process from the ligand of UiO-66-PSM to BBH. The UiO-66-PSM sensor exhibited fast response time, low detection limit, and high selectivity to BBH. Moreover, the UiO-66-PSM sensor was successfully applied to the quantitative detection of BBH in the traditional Chinese herb Coptis, and the detection results obtained from the as-fabricated fluorescence sensing assay were consistent with those of high-performance liquid chromatography (HPLC), indicating that this work has potential applicability for the detection of BBH in traditional Chinese herbs.

The effects of hospice care education on first-year undergraduate nursing students in mainland China: A mixed-methods study.

BACKGROUND: With the rising number of people with end-stage chronic diseases, the demand for hospice care has increased dramatically. As the future health professionals for the implementation of hospice care, undergraduate nursing students in mainland China still lack knowledge and skills of hospice care, thus hospice care education plays a vital role in its development. OBJECTIVES: To understand the effects of hospice care education on nursing students' death attitudes, end-of-life attitudes, humanistic care qualities, and their learning experiences. DESIGN: This study used a mixed-methods design. SETTING: A University of Chinese Medicine in mainland China. PARTICIPANTS: The first-year undergraduate nursing students (n = 65). METHODS: A mixed-methods study was conducted to evaluate the impact of a hospice care course from March to June 2021. The quantitative part included a quasi-experimental study designed with pre- and post-intervention measurements and the qualitative part included a descriptive qualitative study with semi-structured individual interviews. RESULTS: The quantitative data revealed that after the course, nursing students experienced improvements in their death attitudes, end-of-life attitudes, and humanistic care qualities. Two categories were identified from the qualitative data. The category of "Gain from learning" included 4 themes (Confronting death and thinking about life; Understanding and agreeing with the idea of hospice care; Perceiving the humanistic spirit of medicine; Enhancing of the nursing discipline cognition and professional identity) and the category of "Course feedback" included 2 themes (Expressing recognition for the course arrangement; Making suggestions on the course optimization). CONCLUSIONS: Hospice care education had a positive influence on nursing students. Students expressed satisfaction with the course arrangement. However, future hospice care courses should further optimize the curriculum designs by increasing the discussion of death-related topics, sharing more real clinical cases, recruiting students from different majors, and providing clinical practice, to provide high-quality nursing education for the development of hospice care.

Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.

Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.