Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia.

Converging findings have established that the endocannabinoid (eCB) system serves as a possible target for the development of new treatments for pain as a complement to opioid-based treatments. Here we show in male and female mice that enhancing levels of the eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition of its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or in the ventral tegmental area (VTA) with JZL184, leads to a substantial attenuation of the rewarding effects of opioids in male and female mice using conditioned place preference and self-administration paradigms, without altering their analgesic properties. These effects are driven by CB1 receptors (CB1Rs) within the VTA as VTA CB1R conditional knockout, counteracts JZL184's effects. Conversely, pharmacologically enhancing the levels of the other eCB, anandamide (AEA), by inhibition of fatty acid amide hydrolase (FAAH) has no effect on opioid reward or analgesia. Using fiber photometry with fluorescent sensors for calcium and dopamine (DA), we find that enhancing 2-AG levels diminishes opioid reward-related nucleus accumbens (NAc) activity and DA neurotransmission. Together these findings reveal that 2-AG counteracts the rewarding properties of opioids and provides a potential adjunctive therapeutic strategy for opioid-related analgesic treatments.

Real-world effectiveness of molnupiravir, azvudine and paxlovid against mortality and viral clearance among hospitalized patients with COVID-19 infection during the omicron wave in China: A retrospective cohort study.

OBJECTIVES: In this retrospective cohort study, we aimed to assess clinical effectiveness and viral clearance following the use of molnupiravir, azvudine and paxlovid in hospitalized patients with COVID-19 in China dominated by the omicron BA.5.2 and BF.7 subvariant of SARS-CoV-2. METHODS: Enrolled patients were assigned to the molnupiravir group or the azvudine group or the paxlovid group or the control group (not taking any antiviral drugs). The primary outcome of the cohort study was viral clearance and viral burden rebound after treatment and the secondary outcome was 28-day all-cause mortality. The four groups were propensity score-matched (1:1). We plotted viral load trends for each antiviral drug intervention using locally weighted regression (LOWESS) smoothed data. Multivariate logistic regression (stepwise algorithm) models were used to determine any risk factors for 28-day mortality. RESULTS: Of the 1537 patients receiving any treatment, 886 (57.6 %) received molnupiravir, 390 (25.4 %) received azvudine, 94 (6.1 %) received paxlovid, and 167 (10.9 %) did not use any antiviral drugs. Our data analysis showed that age (OR = 1.05, 95 % CI: 1.03-1.07, P < 0.001), Charlson comorbidty index (OR = 1.32, 95 % CI: 1.18-1.48, P < 0.001), severity of COVID-19 (P < 0.001), gamma globulin (OR = 2.04, 95 % CI: 1.03-3.99, P = 0.039) and corticosteroids use (OR = 2.3, 95 % CI: 1.19-4.69, P = 0.017) were independent prognostic factors for 28-day mortality in COVID-19 patients. After propensity score matching (PSM), the paxlovid recipients (OR = 0.22, 95 % CI: 0.05-0.83, P = 0.036) or azvudine recipients (OR = 0.27, 95 % CI: 0.07-0.91, P = 0.046) had lower 28-day mortality compared to their matched controls. Viral rebound occurred in the control group around days 9-16, while no viral rebound was found in any of the three oral antiviral groups. We found that molnupiravir group performed comparably in terms of the rate of nucleic acid conversion negative compared with the paxlovid group, while azvudine group performed slightly worse compared with the paxlovid group or molnupiravir group. CONCLUSIONS: In our retrospective cohort of hospitalized patients with COVID-19 during the wave of omicron strain, the molnupiravir, paxlovid and azvudine recipients showed a faster and more stable decrease in viral load and rare virus rebound in response to antiviral treatments when compared to the controls. The study supported that initiation treatment with paxlovid and azvudine was associated with significantly lower risk of all-cause death within 28 days.

Public perception of cultural ecosystem services in historic districts based on biterm topic model.

Historic districts are integral components of urban space, possessing diverse ecosystems that can offer various cultural services to the public. Urbanization and tourism development have led to the degradation of the ecological landscapes within historic districts, impacting sustainable development. Incorporating Cultural Ecosystem Services (CES) into the environmental research of historic districts can meet people's spiritual needs, enhance intangible benefits for humanity, and promote the conservation of the ecological environment within historic districts. Therefore, this study conducted perceptual quantification research on CES in four typical historic districts in Fuzhou City, crawling the online comment data through Python, mined its potential themes using Biterm Topic Model (BTM), and extracted and categorized the indicators of CES of historic districts by combining with expert consultation; meanwhile, the satisfaction of CES of historic districts is further explored with the help of two methods, namely, sentiment analysis and Importance-Performance analysis (IPA), and summarized the public perception of CES of historic districts. The results of the study show that: (1) the dimensions of public perception of CES in urban historic districts include Cultural Heritage, Leisure Tourism, Aesthetic Enjoyment, Spiritual Fulfillment, Inspiration, and Science Education six indicators, of which Leisure Tourism is most easily perceived by the public, but its satisfaction is not high; (2) the public's perception of positive emotions towards the CES of historic districts in Fuzhou is greater than negative emotions, with positive emotions accounting for 80.61%; (3) the public's overall satisfaction with the CES of Fuzhou's historic districts is high, and according to the final analysis results of the IPA, the four historic districts of Fuzhou are respectively proposed to improve the opinions. Based on big data, this study explores the public perception characteristics of CES in Fuzhou historic districts to promote its sustainable development and improve public well-being, which is of great significance to protecting the ecological environment of historic districts and improving the quality of cultural services.

Non-trade-off Changes in Soil Conservation Service and Soil Loss on the Tibetan Plateau Underlying the Impacts of Climate Change and human activities.

Climate change and human activities have significantly influenced soil loss and the soil conservation service, posed threats to regional ecological sustainability. However, the relationships and underlying driving forces between potential soil loss, actual soil loss, and soil conservation service have not been well understood. Utilizing the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model, we evaluated the soil conservation service on the Tibetan plateau from 1990 to 2020. We analyzed the spatial and temporal trends and examined the driving factors using linear regression, Pearson correlation, and random forest regression. The soil conservation service exhibited a complex pattern of increase followed by a decrease, with a turning point around 2010. Soil conservation service and soil loss demonstrated non-trade-off changes. The potential soil loss dominated the spatiotemporal patterns of soil conservation service on the Tibetan Plateau. Climatic factors significantly influenced the spatiotemporal patterns of soil conservation service, with annual precipitation emerging as the dominant driving factor, contributing approximately 20%. However, the impacts of human activities became more pronounced since 2010, and the contribution of vegetation to changes in soil conservation service was increased. The impact of the Normalized Difference Vegetation Index (NDVI) on soil conservation service for the grades I, II, and III increased by 13.19%, 3.08%, and 3.41%, respectively. Conversely, in northern Tibet before 2010 and eastern Three-River-Source after 2010, soil conservation service exhibited an increasing trend driven by both climate factors and human activities. Which indicates that the implementation of ecological restoration measures facilitated vegetation improvement and subsequently reduced actual soil loss. This study provides a scientific basis for resource management, land development strategies, and the formulation of ecological restoration measures on the Tibetan Plateau.

Electrochemical Oxidative Difunctionalization of Diazo Compounds with Diselenides and Nucleophiles.

An electrochemical oxidative difunctionalization of diazo compounds with diselenides and nucleophiles has been developed. This innovative approach yields a diverse array of selenium-containing pyrazole esters and alkoxy esters, overcoming the limitations of traditional synthesis methods. Remarkably, various nucleophiles, including acids, alcohols, and pyrazoles, can be seamlessly incorporated. Notably, this protocol boasts high atom efficiency, excellent functional group tolerance, and good efficiency and operates under transition metal- and oxidant-free conditions, distinguishing it in the field.

Aquaculture Performance and Genetic Diversity of a New [(Crassostrea hongkongensis ♀ × C. gigas ♂) ♂ × C. hongkongensis ♀] Variety of the Oyster "South China No. 1" in Beibu Gulf, China.

Crassostrea hongkongensis is an economically important bivalve found in various parts of the South China Sea. A new interspecific backcross ([(Crassostrea hongkongensis ♀ × C. gigas ♂) ♂ × C. hongkongensis ♀]) variety was bred by the South China Sea Institute of Oceanology which named "South China No. 1". This study aims to explore the effects of stocking density on the growth performance of "South China No. 1", compared their growth performance and genetic diversity to C. hongkongensis, and found the best place breeding site for "South China No. 1" in Beibu Gulf. The results showed that stocking a density of 20 oysters/substrate can significantly increase the shell height, shell width, total weight, survival rate, daily shell height gain and daily body mass gain. It was found that the shell height and total weight of "South China No. 1" cultured in Fangchenggang were significantly higher than that of those in Beihai and Qinzhou from September 2018 to November 2018. Similarly, the shell width of oysters in Fangchenggang and Qinzhou was also significantly higher in September 2018, and the interaction between site and stocking density had significant effects on the shell width in March 2018 and November 2018. In addition, the shell height and shell width of "South China No. 1" were significantly higher than that of C. hongkongensis in all three sites. At all three sites, the phytoplankton community structure was mostly dominated by Bacillariophyta. In the Hardy-Weinberg equilibrium test, for the seven populations and ten microsatellites, in 10 of the 70 groups, the segregation distortion was significant. These results suggest that a stocking density of 20 oysters/substrate can promote the shell height, shell width and total weight of "South China No. 1" in Beibu Gulf, China. "South China No. 1" has better growth performance compared with C. hongkongensis. Fangchenggang is a suitable place to cultivate the "South China No. 1" breed according to the total weight and sum of all algal genus abundances. The results of this study can be used as a reference to further understand the stocking density and genetic diversity of the "South China No. 1" breed in Beibu Gulf, China.

Incomplete tuberculosis reporting and registration to the surveillance system in southwestern China of Yunnan Province: an inventory survey.

BACKGROUND: The real-world tuberculosis (TB) surveillance data was generally incomplete due to underreporting and underdiagnosis. The inventory study aimed to assess and quantify the incompletion of surveillance systems in southwestern China. METHODS: The inventory study was conducted at randomly selected health facilities (HF) by multi-stage stratified cluster sampling. The participants were included in the period between August of 2020 in province-level and prefecture-level HF, and in the period between June to December of 2020 in other categories of HF respectively. The clinical committee confirmed medical records were matched to the National Notifiable Disease Reporting System (NNDRS) and the Tuberculosis Information Management System (TBIMS) to define the report and register status. The underreporting and under-register rates were evaluated based on the matched data, and factors associated with underreport and under-register were assessed by the 2-level logistic multilevel model (MLM). RESULTS: We enrolled 7,749 confirmed TB cases in the analysis. The province representative overall underreport rate to NNDRS was 1.6% (95% confidence interval, 95% CI, 1.3 - 1.9), and the overall under-register rate to TBIMS was 9.6% (95% CI, 8.9-10.3). The various underreport and under-register rates were displayed in different stratifications of background TB disease burden, HF level, HF category, and data source of the medical record in HF among prefectures of the province. The intraclass correlation coefficient (ICC) was 0.57 for the underreporting null MLM, indicating the facility-level cluster effect contributes a great share of variation in total variance. The two-level logistic MLM showed the data source of medical records in HF, diagnostic category of TB, and type of TB were associated with underreporting by adjusting other factors (p < 0.05). The ICC for under-register was 0.42, and the HF level, HF category, data source of medical records in HF, diagnostic category of TB and type of TB were associated with under-register by adjusting other factors (p < 0.05). CONCLUSION: The inventory study depicted incomplete TB reporting and registering to NNDRS and TBIMS in southwestern China. It implied that surveillance quality improvement would help advance the TB prevention and control strategy.

Correlation Between Blood Urea Nitrogen and Short- and Long-Term Glycemic Variability in Elderly Patients with Type 2 Diabetes Mellitus Who Were hospitalized:A Retrospective Study.

Objective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and progressively impaired insulin secretion resulting in dynamic fluctuations in glucose levels.High blood urea nitrogen (BUN) levels have been linked to decreased insulin sensitivity, suppressed insulin synthesis and increased risk of incident diabetes mellitus in humans as well as insulin use in patients with T2DM.This study characterize the association between BUN levels and short-term and long-term glycemic variability(GV) in the elderly patients with T2DM who were hospitalized. Methods: A total of 927 elderly patients with T2DM were included in the study. The short-term GV was quantified using parameters such as standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), based on multi-point fingertip blood glucose monitoring. The long-term GV was quantified using parameters such as SD, CV, variation independent of the mean (VIM), and average successive variability (ARV), based on fasting blood glucose(FPG). The relationship between BUN levels and short-term and long-term GV in elderly T2DM who were hospitalized was explored using methods such as Spearman correlation coefficient, linear regression analysis, logistic regression analysis, and interaction tests. Results: In elderly patients with T2DM were hospitalized, there is a significant correlation between BUN levels and both short-term and long-term GV. BUN is negatively correlated with the GV parameter TIR (r=-0.12, P=0.000), and positively correlated with SD (r=0.12, P=0.000), CV (r=0.07, P=0.026), MAGE (r=0.11, P=0.001), FPG-SD (r=0.08, P=0.013), and FPG-CV (r=0.08, P=0.014).Furthermore, the association remains consistent across different age, gender, BMI, and haemoglobin A1c (HbA1c) subgroups (P interaction > 0.05). Conclusion: In elderly patients with T2DM were hospitalized, BUN levels were positively associated with GV.Therefore, monitoring BUN levels were beneficial in assessing the degree of GV.

Generalization of a Deep Learning Model for Continuous Glucose Monitoring-Based Hypoglycemia Prediction: Algorithm Development and Validation Study.

Background: Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. Objective: The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. Methods: We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results: For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms. Conclusions: Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction.

25(OH)D level and vascular lesion scores in kidney histopathology as risk-stratification tool for predicting renal progression in people with type 2 diabetes.

AIM: To evaluate the potential of the combined individual vascular histopathological lesion and serum 25-hydroxy vitamin D [25(OH)D] level as predictors of outcomes in patients with diabetes and chronic kidney disease. METHODS: A total of 190 patients with type 2 diabetes and kidney disease stages 1-4 were retrospectively included. Kaplan-Meier analysis and the log-rank test were performed to assess renal survival differences. And the time-dependent receiver operating characteristic analyses were used to characterize the predictive accuracy. Hazard ratios for vascular lesion scores and 25(OH)D levels with renal outcomes were estimated using Cox proportional hazards regression models with follow-up time. RESULTS: Over a median follow-up of 23.78 (12.61, 37.14) months, 71 patients (37.4 %) experienced the renal outcomes. Enrolled patients with more severe vascular lesions had worse kidney function, heavier proteinuria, lower serum 25(OH)D levels, and higher prevalence of composite kidney outcomes. Baseline serum 25(OH)D was a significant independent risk factor for vascular lesion scores. The effect of serum 25(OH)D level on kidney prognosis was more pronounced in males and those with more exacerbated vascular lesions (score 2). The severity of vascular lesions and serum 25(OH)D levels were associated with unfavorable kidney outcomes. Accordingly, further time-dependent receiver operating characteristic curves confirmed that combined 25(OH)D level and vascular lesion score had a stable and reliable performance in renal outcomes prediction at short and long-term follow-up times. CONCLUSIONS: 25(OH)D level and vascular lesion scores in kidney histopathology could serve as a useful risk-stratification tool for predicting renal progression in patients with type 2 diabetes.

Association of histone modification with the development of schizophrenia.

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

Work experience of breastfeeding nurses returning to work after maternity leave in Liaoning Province of China: A qualitative study.

AIM: With the implementation of China's three-child policy in 2021, the nurse population faces an increase in the number of breastfeeding nurses returning to work after maternity leave. This study aims to describe the work experience of breastfeeding nurses returning to work after maternity leave. DESIGN: A qualitative descriptive design. METHODS: The data were collected through semi-structured interviews with eight nurses and analysed through Braun and Clarke's thematic analysis. RESULTS: Three themes and nine sub-themes emerged from the analysis of the interviews: changes in nurses (emotional changes, physical changes and changes in work); needs for an improving work environment (needs for a supportive workplace and nurse shortage); support for breastfeeding nurses (support from coworkers, support from the manager, support from the organisation and own need for work). PUBLIC CONTRIBUTION: This study highlighted that breastfeeding nurses need an adjustment period when they return to work after maternity leave. Successful breastfeeding requires support from coworkers, managers and the organisation. In addition, workplace support for breastfeeding and management for nurses needs to be improved.

Phosphorus stoichiometric homeostasis of submerged macrophytes and associations with interspecific interactions and community stability in Erhai Lake, China.

According to stoichiometric homeostasis theory, eutrophication is expected to increase the dominance of submerged macrophytes with low homeostatic regulation coefficients (H) relative to those with high H values, ultimately reducing macrophyte community stability. However, empirical evidence supporting this hypothesis is limited. In this study, we conducted a three-year tracking survey (seven sampling events) at 81 locations across three regions of Erhai Lake. We assessed the H values of submerged macrophyte species, revealing significant H values for phosphorus (P) and strong associations of HP values (range: 1.58-2.94) with species and community stability. Moreover, in plots simultaneously containing the dominant high-HP species, Potamogeton maackianus, and its low-HP counterpart, Ceratophyllum demersum, we explored the relationships among eutrophication, interspecific interaction shifts, and community dynamics. As the environmental P concentration increased, the dominance of P. maackianus decreased, while that of C. demersum increased. This shift coincided with reductions in community HP and stability. Our study underpins the effectiveness of H values for forecasting interspecific interactions among submerged macrophytes, thereby clarifying how eutrophication contributes to the decline in stability of the submerged macrophyte community.

Visible light-driven photocatalytic sulfonative oxidation of benzyl secondary amines.

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.

Single-Atom Iron Catalyst as an Advanced Redox Mediator for Anodic Oxidation of Organic Electrosynthesis.

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

Development and validation of models for predicting mortality in intertrochanteric fracture surgery patients with perioperative blood transfusion: a prospective multicenter cohort study.

BACKGROUND: The association between allogenic blood transfusions (ABT) and all-cause mortality in surgically treated hip fracture patients with perioperative transfusion (STHFPT) remained unknown. We aim to introduce transfusion-related factors, new variables to develop and validate models to predict mortality in these patients. METHODS: A prospective multicenter cohort study was conducted with STHFPT hospitalized during Jan. 2018 and Jun. 2021. The database was divided into training cohort and validation cohort in a ratio of 70% to 30% using the randomization method. All participants received a minimum of 2-year follow-up and all participants' overall and eight time-specific survival status were recorded. Prediction models were developed using multivariate logistic regression and Cox regression for variable selection. Model performance was measured by determining discrimination, calibration, overall model performance or precision, and utility. Sensitivity analyses were performed to test robustness of the results. RESULTS: A total of 7074 consecutive patients were prospectively screened and assessed for eligibility to participate. Finally, 2490 patients met our inclusion and exclusion criteria and 1743 (70%) patients were randomized to the training cohort and 747 (30%) to the validation cohort. The median duration of follow-up was 38.4 months (IQR 28.0-62.0). Our novel models highlight that preoperative transfusion is of significance for short-term mortality while mid-term outcomes are predominantly determined by severe complications, pulmonary complications, and advanced age. Our models showed high discriminative power, good calibration and precision for mortality prediction in both training and validation cohorts, especially in short-term mortality prediction. CONCLUSIONS: We introduce transfusion-related factors, new variables to develop and validate models to predict mortality with STHFPT. The models can be further tested and updated with the ultimate goal of assisting in optimizing individual transfusion strategy.

[Analysis of constituents in different parts of Forsythia suspensa by UPLC-Q-TOF-MS and evaluation of their anti-inflammatory activity].

This study aims to characterize and identify the chemical constituents in 11 parts of Forsythia suspensa by using ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with a self-established chemical constituent database, including leaves, flowers, fruits, green F. suspensa, old F. suspensa, and seeds. The quality attributes and differences of different parts of F. suspensa were evaluated by principal component analysis, partial least square discriminant analysis, and other stoichiometric methods. A total of 79 compounds were identified, including 13 phenylethanol glycosides, 10 lignans, 12 flavonoids, 10 organic acids, 14 terpenoids, and 20 other types of compounds. Among them, 34 compounds were the main variables of difference between the different parts of F. suspensa, and the content of each component was relatively higher in the leaves and green F. suspensa. The LPS-induced inflammation model of RAW264.7 cells was applied to study the anti-inflammatory activity of the extracts of the different parts of F. suspensa and the main constituents. The results show that the extracts of green F. suspensa, flower, twig, and stem exhibited anti-inflammatory activity, and the constituents such as forsythoside A, phyllyrin, phillygenin, and(+)-pinoresinol-ß-D-glucopyranoside could significantly inhibit anti-inflammatory activity released by NO. The chemical constituent in different parts of F. suspensa is analyzed comprehensively, and the anti-inflammatory activity is evaluated in this study, which provides a reference for the development and comprehensive utilization of F. suspensa resources.

Designing a Mitochondria-Targeted Theranostic Cyclometalated Iridium(III) Complex: Overcoming Cisplatin Resistance and Inhibiting Tumor Metastasis through Necroptosis and Immune Response.

To develop a potential theranostic metal agent to reverse the resistance of cancer cells to cisplatin and effectively inhibit tumor growth and metastasis, we proposed to design a cyclometalated iridium (Ir) complex based on the properties of the tumor environment (TME). To the end, we designed and synthesized a series of Ir(III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes by modifying the hydrogen atom(s) of the N-3 position of 2-hydroxy-1-naphthaldehyde thiosemicarbazone compounds and the structure of cyclometalated Ir(III) dimers and then investigated their structure-activity and structure-fluorescence relationships to obtain an Ir(III) complex (Ir5) with remarkable fluorescence and cytotoxicity to cancer cells. Ir5 not only possesses mitochondria-targeted properties but also overcomes cisplatin resistance and effectively inhibits tumor growth and metastasis in vivo. Besides, we confirmed the anticancer mechanisms of Ir5 acting on different components in the TME: directly killing liver cancer cells by inducing necroptosis and activating the necroptosis-related immune response.

Advances in the Effects of Dietary Macronutrients on the Gut Microbiota of Tilapia (Oreochromis spp.).

The homeostasis of the intestinal microbiota of fish is beneficial to fish health, while food can affect the intestinal microbiota. Tilapia (Oreochromis spp.) has great economic value and is a good model to use in studying the digestion and absorption of nutrients. Furthermore, at present, due to a high demand and high price of high-quality feed raw materials, the nutritional composition of aquafeeds has been changing dynamically. There has yet to be a comprehensive review of research conducted on the influences of dietary macronutrients (proteins, lipids, and carbohydrates) on the tilapia intestinal microbiota. Therefore, this review focuses on the effects of dietary macronutrients on the gut microbiota of tilapia. Interestingly, we found that the best growth performance might not represent the best composition or functions of the gut microbiota. Overall, the unscientific addition of macronutrients to feed is harmful to the intestinal microbiota. Therefore, both growth performance and gut microbiota should be considered when evaluating certain macronutrients. It is our hope that this review will aid in regulating the intestinal microbiota of fish through nutritional means, thereby promoting tilapia farming.