Metabolomics reveals the importance of metabolites in Mussaenda pubescens for antioxidant properties and quality traits.

Mussaenda pubescens (Mp) is a valuable medicinal plant that has traditionally been used for medicinal purposes or as a tea substitute. However, there are few studies on the comprehensive and dynamic evaluation of Mp metabolites. This study used an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach and biochemical analysis to investigate substance changes in leaves at three different stages and elucidate the relationship between metabolites and antioxidant capacity. The findings showed that Mp leaves contained 957 metabolites, the majority of which were phenolic acids, lipids, and terpenoids. The metabolite profiling of Mp leaves was significantly influenced by their growth and development at different stages. A total of 317 differentially accumulated metabolites (DAMs) were screened, including 150 primary metabolites and 167 secondary metabolites, with 202 DAMs found in bud leaf vs. tender leaf, 54 DAMs in tender leaf vs. mature leaf, and 254 DAMs in bud leaf vs. mature leaf. Total phenolics, flavonoids, and anthocyanin concentrations decreased as Mp leaves grew and developed, whereas terpenoids increased significantly. The secondary metabolites also demonstrated a positive correlation with antioxidant activity. Phenolics, flavonoids, terpenoids, and anthocyanins were the primary factors influencing the antioxidant activity of leaves. These findings provide new insights into the metabolite formation mechanism, as well as the development and utilization of Mp tea.

An Inductive Reasoning Model based on Interpretable Logical Rules over temporal knowledge graph.

Extrapolating future events based on historical information in temporal knowledge graphs (TKGs) holds significant research value and practical applications. In this field, the methods currently utilized can be classified as either embedding-based or logical rule-based. Embedding-based methods depend on learned entity and relation embeddings for prediction, but they suffer from the lack of interpretability due to the opaque reasoning process. On the other hand, logical rule-based methods face scalability challenges as they heavily rely on predefined logical rules. To overcome these limitations, we propose a hybrid model that combines embedding-based and logical rule-based methods to capture deep causal logic. Our model, called the Inductive Reasoning Model based on Interpretable Logical Rule (ILR-IR), aims to provide interpretable insights while effectively predicting future events in TKGs. ILR-IR delves into historical information, extracting valuable insights from logical rules embedded within relations and interaction preferences between entities. By considering both logical rules and interaction preferences, ILR-IR offers a comprehensive perspective for predicting future events. In addition, we propose the incorporation of a one-class augmented matching loss during optimization, which serves to enhance performance of the model during training. We evaluate ILR-IR on multiple datasets, including ICEWS14, ICEWS0515, and ICEWS18. Experimental results demonstrate that ILR-IR outperforms state-of-the-art baselines, showcasing its superior performance in TKG extrapolation reasoning. Moreover, ILR-IR demonstrates remarkable generalization capabilities, even when applied to related datasets that share a common relation vocabulary. This suggests that our proposed model exhibits robust zero-shot reasoning abilities. For interested parties, we have made our code publicly available at https://github.com/mxadorable/ILR-IR.

Distribution and antimicrobial resistance patterns of urinary pathogens in preoperative midstream urine cultures from Chinese patients with urinary calculi: a meta-analysis.

BACKGROUND AND OBJECTIVE: This study comprehensively evaluates the distribution patterns and antimicrobial resistance profiles of urinary pathogens in Preoperative midstream urine cultures collected from patients with urinary calculi in China over the last two decades. METHODS: A cross-sectional analysis of 41 studies was conducted. A systematic search across various databases, including Wanfang Data, CNKI, SinoMed, Embase, PubMed, and Web of Science, was carried out, covering the time period from 2002 to 2022. Using R 4.2.1 software, a meta-analysis was performed to assess heterogeneity using Cochran's Q test and the I2 statistic. RESULTS: In the analysis of preoperative midstream urine cultures from Chinese patients with urinary calculi, gram-negative bacteria dominated at 69%, with Escherichia coli (43%), Klebsiella pneumoniae (8%), Proteus mirabilis (6%), Pseudomonas aeruginosa (5%), Acinetobacter baumannii (3%), and Enterobacter cloacae (4%) being prominent. Gram-positive organisms included Enterococcus faecalis (9%), Enterococcus faecium (5%), and Staphylococcus aureus (4%). Over time, proportions of Proteus mirabilis, Enterococcus faecalis, and Staphylococcus aureus decreased, while Klebsiella pneumoniae and Pseudomonas aeruginosa increased. Notably, Escherichia coli proportion reduced from 37 to 33% within the last two decades. Antimicrobial resistance analysis indicated declining resistance in E. coli (e.g., co-trimoxazole from 73 to 55%, gentamicin from 64 to 40%), but rising resistance in piperacillin and cefotaxime (34-60%). Enterococcus faecalis exhibited increasing resistance to ampicillin (5-69%), gentamicin (59-94%), and tetracycline (77-89%) over time, while resistance to levofloxacin and ciprofloxacin notably decreased (72-16% and 49-8%, respectively). CONCLUSION: Over the past two decades, the proportion of gram-negative bacteria was declined, while the proportion of gram-positive bacteria increased. Escherichia coli remained the most common pathogen in the urine culture of patients with urinary calculi in China and the resistance of Escherichia coli to commonly used antibiotics increased. Clinicians should select appropriate antibiotics according to the results of urine culture and drug sensitivity test to reduce the occurrence of antibiotic resistance.

Screening of Sugarcane Proteins Associated with Defense against Leifsonia xyli subsp. xyli, Agent of Ratoon Stunting Disease.

Sugarcane is the most important sugar crop and one of the leading energy-producing crops in the world. Ratoon stunting disease (RSD), caused by the bacterium Leifsonia xyli subsp. xyli, poses a huge threat to ratoon crops, causing a significant yield loss in sugarcane. Breeding resistant varieties is considered the most effective and fundamental approach to control RSD in sugarcane. The exploration of resistance genes forms the foundation for breeding resistant varieties through molecular technology. The pglA gene is a pathogenicity gene in L. xyli subsp. xyli, encoding an endopolygalacturonase. In this study, the pglA gene from L. xyli subsp. xyli and related microorganisms was analyzed. Then, a non-toxic, non-autoactivating pglA bait was successfully expressed in yeast cells. Simultaneously the yeast two-hybrid library was generated using RNA from the L. xyli subsp. xyli-infected sugarcane. Screening the library with the pglA bait uncovered proteins that interacted with pglA, primarily associated with ABA pathways and the plant immune system, suggesting that sugarcane employs these pathways to respond to L. xyli subsp. xyli, triggering pathogenicity or resistance. The expression of genes encoding these proteins was also investigated in L. xyli subsp. xyli-infected sugarcane, suggesting multiple layers of regulatory mechanisms in the interaction between sugarcane and L. xyli subsp. xyli. This work promotes the understanding of plant-pathogen interaction and provides target proteins/genes for molecular breeding to improve sugarcane resistance to L. xyli subsp. xyli.

CREB: A Promising Therapeutic Target for Treating Psychiatric Disorders.

Psychiatric disorders are complex, multifactorial illnesses. It is challenging for us to understand the underlying mechanism of psychiatric disorders. In recent years, the morbidity of psychiatric disorders has increased yearly, causing huge economic losses to the society. Although some progress, such as psychotherapy drugs and electroconvulsive therapy, has been made in the treatment of psychiatric disorders, including depression, anxiety, bipolar disorder, obsessive-compulsive and autism spectrum disorders, antidepressants and psychotropic drugs have the characteristics of negative effects and high rate of relapse. Therefore, researchers continue to seek suitable interventions. cAMP response element binding protein (CREB) belongs to a protein family and is widely distributed in the majority of brain cells that function as a transcription factor. It has been demonstrated that CREB plays an important role in neurogenesis, synaptic plasticity, and neuronal growth. This review provides a 10-year update of the 2013 systematic review on the multidimensional roles of CREB-mediated transcriptional signaling in psychiatric disorders. We also summarize the classification of psychiatric disorders and elucidate the involvement of CREB and related downstream signalling pathways in psychiatric disorders. Importantly, we analyse the CREB-related signal pathways involving antidepressants and antipsychotics to relieve the pathological process of psychiatric disorders. This review emphasizes that CREB signalling may have a vast potential to treat psychiatric disorders like depression. Furthermore, it would be helpful for the development of potential medicine to make up for the imperfection of current antidepressants and antipsychotics.

Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial.

Importance: The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear. Objective: To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases. Design, Setting, and Participants: This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with ERBB2-positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023. Interventions: Patients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg/m2, twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects. Main Outcomes and Measures: The primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function. Results: A total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points. Conclusions and Relevance: The results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with ERBB2-positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation. Trial Registration: ClinicalTrials.gov Identifier: NCT04582968.

Noncovalent Conjugates of Anthocyanins to Wheat Gluten: Unraveling Their Microstructure and Physicochemical Properties.

Intake of polyphenol-modified wheat products has the potential to reduce the incidence of chronic diseases. In order to determine the modification effect of polyphenols on wheat gluten protein, the effects of grape skin anthocyanin extract (GSAE, additional amounts of 0.1%, 0.2%, 0.3%, 0.4%, and 0.5%, respectively) on the microstructure and physicochemical properties of gluten protein were investigated. The introduction of GSAE improves the maintenance of the gluten network and increases viscoelasticity, as evidenced by rheological and creep recovery tests. The tensile properties of gluten protein were at their peak when the GSAE level was 0.3%. The addition of 0.5% GSAE may raise the denaturation temperature of gluten protein by 6.48 °C-9.02 °C at different heating temperatures, considerably improving its thermal stability. Furthermore, GSAE enhanced the intermolecular hydrogen bond of gluten protein and promoted the conversion of free sulfhydryl groups to disulfide bonds. Meanwhile, the GSAE treatment may also lead to protein aggregation, and the average pore size of gluten samples decreased significantly and the structure became denser, indicating that GSAE improved the stability of the gluten spatial network. The positive effects of GSAE on gluten protein properties suggest the potential of GSAE as a quality enhancer for wheat products.

HINT2 may be One Clinical Significance Target for Patient with Diabetes Mellitus and Reduced ROS-Induced Oxidative Stress and Ferroptosis by MCU.

The World Health Organization (WHO) predicted that patients with diabetes around the world will increase to 600 million by 2040, of which about 1/3 will develop diabetic nephropathy (DN). Therefore, the present study aimed to uncover therapeutic effect of HINT2 and determined its possible mechanisms. Patients with diabetes mellitus and normal volunteers were enrolled at our hospital. Male C57BL/6 mice were fed with a high fat diet and injected intraperitoneally with STZ for once (100 mg/kg body weight). Mouse podocytes (MPC5) cells were induced with 20 mmol/l D-glucose. Inhibition of HINT2 mRNA expression levels in patients with DN was observed, compared with normal group. The serum of HINT2 mRNA expression was negative in correlation with blood sugar, tubulo-interstitial damage, glomerular damage score or urine protein level in patients with DN. HINT2 expression in kidney tissue of mice with DN were downregulated. HINT2 presented reduced DN and inflammation and ROS-induced oxidative stress in model of DN. HINT2 promoted ferroptosis in model of DN by mitochondrial membrane potential. HINT2 suppressed MCU expression in model of DN. HINT2 protein combined with MCU protein increased MCU protein ubiquitination. HINT2 triggers mitochondrial Ca2+ influx to increase ROS production level by MCU. Taken together, these findings demonstrated that HINT2 reduced ROS-induced Oxidative stress and ferroptosis by MCU, suggesting that HINT2 may be a feasible strategy to treat DN.

Adjuvant medial versus entire supraclavicular lymph node irradiation in high-risk early breast cancer (SUCLANODE): a protocol for a multicenter, randomized, open-label, phase 3 trial.

BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .

Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal LINC01963 to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells.

BACKGROUND: Hyperglycemia is widespread in the world's population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. METHODS: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1ß, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. RESULTS: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1ß, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1ß, IL-18, ROS, MDA, and LDH. CONCLUSION: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

The Changes in Metabolites, Quality Components, and Antioxidant Activity of Tea (Camellia sinensis) Infected with Exobasidium vexans by Applying UPLC-MS/MS-Based Widely Targeted Metabolome and Biochemical Analysis.

Blister blight infection with Exobasidium vexans is one of the most destructive foliar diseases that seriously affect the quality and yield of tea. This research investigated the metabolite changes of healthy and infected leaves on tea cultivar 'Fuding Dabaicha' and further explored the potential antimicrobial substances against E. vexans infection. In total, 1,166 compounds were identified during the entire course of an infection, among which 73 different common compounds were significantly accumulated involved in the important antimicrobial substances of flavonoids and phenolic acids, including kaempferol (3,5,7,4'-tetrahydroxyflavone), kaempferol-3-O-sophoroside-7-O-glucoside, phloretin, 2,4,6-trihydroxybenzoic acid, galloylprocyanidin B4, and procyanidin C1 3'-O-gallate, which indicated that these metabolites might positively dominate resistance to E. vexans. Furthermore, relevant biological pathways, such as the flavone and flavonol biosynthesis, flavonoid biosynthesis, and phenylpropane pathways, were more closely related to resistance to E. vexans. Additionally, total flavonoids, phenolics, alkaloids, and terpenoids contributing to antimicrobial and antioxidant capacity were significantly altered during four different infection periods, especially the Leaf_S2 stage (the second stage of infection), in which the most concentration accumulated. The leaves affected by E. vexans infection at the second stage had the relatively highest antioxidant activity. Accordingly, this study provides a theoretical support for and comprehensive insights into the effects on the metabolite changes, tea quality components, and antioxidant activity of blister blight caused by E. vexans.

[Spatiotemporal Distribution Characteristics of Air Pollution and Health Risks in Key Cities of China].

Based on the monitoring data of five pollutants in 168 key cities under air pollution prevention and control in China from 2015 to 2020, using the MAKESENS model and the aggregate risk index(ARI), this study quantitatively analyzed the spatial and temporal distribution characteristics of air pollution and health risks in China and the six urban agglomerations. The results showed that:① PM2.5 pollution was the most serious pollution in Chinese key cities. Only 15% of the cities' six-year average concentrations of PM2.5 reached the National Secondary Standard, followed by that of NO2; 77% of the cities' six-year average concentrations of NO2 reached the National Secondary Standard. The urban agglomerations of Beijing-Tianjin-Hebei and Fenwei plain had the most serious air pollution, and the six-year average concentrations of PM2.5, SO2, CO, and NO2 were higher than those of other urban agglomerations. ② The concentrations of PM2.5, SO2, CO, and NO2 in key cities of China showed a decreasing trend, whereas the concentration of O3 in other urban agglomerations showed an increasing trend, except in the Chengdu-Chongqing urban agglomeration. The concentration of SO2 in the urban agglomerations of Beijing-Tianjin-Hebei and Fenwei plain changed the most significantly. ③ The health risk of air pollution in the key cities of China generally showed a decreasing trend, with a sharp decline from 2017 to 2018, and the population exposed to extremely high risks dropped from 160 million to 32.54 million. The urban agglomeration in the middle reaches of the Yangtze River had the most significant decline in health risks, whereas the key cities in China faced higher health risks in spring and winter seasons. ④ The Beijing-Tianjin-Hebei and Fenwei plain urban agglomerations had the highest health risks, and the urban agglomeration in the middle reaches of the Yangtze River had the lowest; O3 gradually replaced PM2.5 as the main pollutant affecting the health risk. These results can provide a reference for evaluating the effectiveness of urban air pollution control in China during the 13th Five-Year Plan period.

Phenolic Profile and Bioactivity Changes of Lotus Seedpod and Litchi Pericarp Procyanidins: Effect of Probiotic Bacteria Biotransformation.

Theoretically, lactic acid bacteria (LABs) could degrade polyphenols into small molecular compounds. In this study, the biotransformation of lotus seedpod and litchi pericarp procyanidins by Lactobacillus plantarum 90 (Lp90), Streptococcus thermophilus 81 (ST81), Lactobacillus rhamnosus HN001 (HN001), and Pediococcus pentosus 06 (PP06) were analysed. The growth curve results indicated that procyanidins did not significantly inhibit the proliferation of LABs. Ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS) revealed that procyanidin B2 and procyanidin B3 in lotus seedpod decreased by 62.85% and 25.45%, respectively, with ST81 metabolised, while kaempferol and syringetin 3-O-glucoside content increased. Although bioconversion did not increase the inhibitory function of procyanidins against glycosylation end-products in vitro, the 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) free radical scavenging capacity and ferric reducing antioxidant power of litchi pericarp procyanidins increased by 157.34% and 6.8%, respectively, after ST81 biotransformation. These findings may inspire further studies of biological metabolism of other polyphenols and their effects on biological activity.

RhB-Embedded Mn-MOF with Cyclotriphosphazene Skeleton as Dual-Emission Sensor for Putrescine as well as Smart Fluorescent Response of Aromatic Diamines and Nitrophenol.

Luminescent metal-organic framework composites with multiple luminescence emissions have been efficient sensing platforms. Herein, a fluorescent sensor (RhB@1-0.4) with dual-emission fluorescence properties was prepared by introducing rhodamine B (RhB) into the framework of complex 1, [Mn2.5(HCPCP)(H2O)4]·(CH3CN)0.5 [HCPCP = hexa-(4-carboxyl-phenoxy)-cyclotriphosphazene and CH3CN = acetonitrile), which is a novel crystalline two-dimensional (2D) coordinated organic framework material. It is a highly desirable material, realizing a ratiometric fluorescence response to putrescine with a high signal-to-noise ratio, and the detection limit can be as low as 6.8 µM. In addition, RhB@1-0.4 exhibited a better fluorescent sensing performance for aromatic diamines and nitrophenols compared with that of complex 1. It is a potential functionalized MOF material for the application of multichannel fluorescence sensing.

Attitudes and Practices Surrounding Opioid Prescriptions following Open Reduction Internal Fixation of Distal Radius and Ankle Fractures: A Survey of the Canadian Orthopaedic Association Membership.

Background: The past two decades have seen a significant increase in consequences associated with nonmedical misuse of prescription opioids, such as addiction and unintentional overdose deaths. This study aimed to use an electronic survey to assess attitudes and opioid-prescribing practices of Canadian orthopaedic surgeons and trainees following open reduction internal fixation (ORIF) of distal radius and ankle fractures. This study was the first to assess these factors following ORIF of distal radius and ankle fractures using a survey design. Methods: A 40-item survey was developed focusing on four themes: respondent demographics, opioid-prescribing practice, patients with substance use disorders, and drug diversion. The survey was distributed among members of the Canadian Orthopaedic Association. Descriptive statistics were used to summarize respondent demographics and outcomes of interest. A Chi-square test was used to determine if proportion of opioid prescriptions between attending surgeons and surgeons in training was equal. Results: 191 surveys were completed. Most respondents prescribed 10-40 tabs of immediate-release opioids, though this number varied considerably. While most respondents believed patients consumed only 40-80% of the prescribed opioids (73.6%), only 28.7% of respondents counselled patients on safe storage/disposal of leftover opioids. 30.5% of respondents felt confident in their knowledge of opioid use and mechanisms of addiction. Most respondents desired further education on topics such as procedure-based opioid-prescribing protocols (74.2%), alternative pain management strategies (69.7%), and mechanisms of opioid addiction (49.0%). Conclusions: The principle finding of this study is the lack of a standardized approach to postoperative prescribing in distal radius and ankle fractures, illustrated by the wide range in number of opioids prescribed by Canadian orthopaedic surgeons. Our data suggest a trend towards overprescription among respondents following distal radius and ankle ORIF. Future studies should aim to rationalize interventions targeted at reducing postoperative opioid prescribing for common orthopaedic trauma procedures.

Effects of degree of milling on nutritional quality, functional characteristics and volatile compounds of brown rice tea.

This study investigated the effects of rice preparation using different degrees of milling (DOM) from 0% to 13% on the nutritional composition, functional properties, major volatile compounds and safety of brown rice tea (BRT). We found that 2% DOM reduced 52.33% of acrylamide and 31.88% of fluorescent AGEs. When DOM was increased from 0% to 13%, the total phenolic content (TPC) of brown rice tea decreased by 48.12%, and the total flavonoid content (TFC) and condensed tannin content (CTC) also decreased significantly, with the smallest decrease at 2% DOM. In addition, the inhibitory activities of α-amylase, α-glucosidase and pancreatic lipase as well as the antioxidant activity also decreased gradually. Analysis by electronic nose and gas chromatography-mass spectrometry (GC-MS) showed that alkanes, furans, aldehydes, pyrazines and alcohols were the major volatiles in BRT, with 2% DOM having the greatest retention of aroma compounds. An orthogonal partial least squares discriminant analysis (OPLS-DA) and VIP score (VIP > 1 and p < 0.05) analysis were used to screen 25 flavor substances that contributed to the differences in BRT aroma of different DOMs. These results suggest that 2% milled BRT can improve safety and palatability while maximizing the retention of flavor compounds and nutrients. The findings of this study contribute to an enhanced understanding of the dynamics of changes and preservation of aroma compounds and nutrients present during the processing of BRT.

Inosine enhances tumor mitochondrial respiration by inducing Rag GTPases and nascent protein synthesis under nutrient starvation.

Metabolic heterogeneity of tumor microenvironment (TME) is a hallmark of cancer and a big barrier to cancer treatment. Cancer cells display diverse capacities to utilize alternative carbon sources, including nucleotides, under poor nutrient circumstances. However, whether and how purine, especially inosine, regulates mitochondrial metabolism to buffer nutrient starvation has not been well-defined yet. Here, we identify the induction of 5'-nucleotidase, cytosolic II (NT5C2) gene expression promotes inosine accumulation and maintains cancer cell survival in the nutrient-poor region. Inosine elevation further induces Rag GTPases abundance and mTORC1 signaling pathway by enhancing transcription factor SP1 level in the starved tumor. Besides, inosine supplementary stimulates the synthesis of nascent TCA cycle enzymes, including citrate synthesis (CS) and aconitase 1 (ACO1), to further enhance oxidative phosphorylation of breast cancer cells under glucose starvation, leading to the accumulation of iso-citric acid. Inhibition of the CS activity or knockdown of ACO1 blocks the rescue effect of inosine on cancer survival under starvation. Collectively, our finding highlights the vital signal role of inosine linking mitochondrial respiration and buffering starvation, beyond serving as direct energy carriers or building blocks for genetic code in TME, shedding light on future cancer treatment by targeting inosine metabolism.

Favorable prognosis of breast cancer brain metastases patients with limited intracranial and extracranial metastatic lesions.

BACKGROUND: Breast cancer brain metastases (BCBM) are highly heterogenous with widely differing survival. The prognosis of the oligometastatic breast cancer (BC) patients with brain metastases (BM) has not been well studied. We aimed to investigate the prognosis of BCBM patients with limited intracranial and extracranial metastatic lesions. METHODS: Four hundred and forty-five BCBM patients treated between 1st January 2008 and 31st December 2018 at our institute were included. Clinical characteristics and treatment information were obtained from patient's medical records. The updated breast Graded Prognostic Assessment (Breast GPA) was calculated. RESULTS: The median OS after diagnosis of BM were 15.9 months. Median OS for patients with GPA 0-1.0, 1.5-2, 2.5-3 and 3.5-4 were 6.9, 14.2, 21.8, 42.6 months respectively. The total number of intracranial and extracranial metastatic lesions, in addition to the Breast GPA, salvage local therapy and systemic therapy (anti-HER2 therapy, chemotherapy and endocrine therapy) were demonstrated to be associated with prognosis. One hundred and thirteen patients (25.4%) had 1-5 total metastatic lesions at BM diagnosis. Patients with 1-5 total metastatic lesions had a significantly longer median OS of 24.3 months compared to those with greater than 5 total metastatic lesions with a median OS of 12.2 months (P < 0.001; multivariate HR 0.55, 95% CI, 0.43-0.72). Among the patients with 1-5 metastatic lesions, median OS for GPA 0-1.0 was 9.8 months, compared to 22.8, 28.8 and 71.0 for GPA 1.5-2.0, 2.5-3.0 and 3.5-4.0 respectively, which is much longer than the corresponding patients with greater than 5 total metastatic lesions, with medium OS of 6.8, 11.6, 18.6 and 42.6 months respectively for GPA 0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0. CONCLUSIONS: The patients with 1-5 total metastatic lesions demonstrated better OS. The prognostic value of the Breast GPA and the survival benefit of salvage local therapy and continuation of systemic therapy after BM were confirmed.

Insights into nutrition, flavor and edible quality changes of golden pomfret (Trachinotus ovatus) fillets prepared by different cooking methods.

Introduction: In recent years, Asia has seen an increase in demand for golden pomfret (Trachinotus ovatus). Especially in instant (ready-to-eat) and prepared (ready-to-cock) food processing industry. Thermal processing is a vital part of food processing. However, no comprehensive analysis has been reported on its flavor, nutrition and edible quality changes during the key thermal processing. Methods: Accordingly, in this study, we evaluated the effects of different cooking methods (steaming, frying, microwaving and baking) on the color, texture, cooking loss, nutrition composition, volatile flavor substances and other indicators of golden pomfret filets. Results and Discussion: The results showed that the steamed samples (SS) had the lowest cooking loss and fat content, the highest moisture content, complete appearance and the lowest levels of hardness and chewiness. Fried samples (FS) had a notable difference in fatty acid composition. The content of unsaturated fatty acids (UFAs) increased significantly, while the relative content of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) decreased from 7.88 to 1.42%, lower than other groups. The essential amino acid index (EAAI) of microwaved samples (MS) was 94.89, which was higher than other groups. Baked samples (BS) had the highest relative content of umami amino acids (UAAs) and sweet amino acids (SAAs), which was 8.08 mg/100 mg and 5.19 mg/100 mg, respectively. Hexanal and nonanal were detected in control samples (CK), SS, FS, MS and BS. While pyrazine compounds were detected only in FS and BS. Steaming and microwaving treatment of golden pomfret resulted in better nutritional preservation, which was more conducive to human health. Frying and baking treatment of golden pomfret had better taste and flavor and higher sensory scores. The nutrition, flavor and edible quality of golden pomfret under different cooking methods were related and interactive. Cooking loss and fat content can be used as simple evaluation indicators to compare the overall quality of different cooking methods. This study provides a reference for the thermal processing technology and industrial production of golden pomfret.

Copper-Mediated and Palladium-Catalyzed Cross-Coupling of Indoles and N-Methylpyridinium Salts: A Practical Way to Prepare 3-(Pyridin-2-yl)indoles.

Herein, a Pd/Cu bimetallic-catalyzed direct C-H heteroarylation of pyridines via the traceless protecting group strategy is described. A series of N-methyl-activated pyridines and 1-methylindoles are coupled with high regioselectivity to produce the corresponding 3-(pyridin-2-yl)indoles in moderate to good yields, wherein related electron-rich heterocycles (e.g., indole, 1-methylpyrrole, benzofuran, benzo[b]thiophene) are also applicable. Streamlined operation, good functional group tolerance, and late-stage modifications make this twofold C-H activation protocol an attractive route for the synthesis of 3-(pyridin-2-yl)indole derivatives.