Genetic structure and selective sweeps in Kirghiz sheep using SNP50K bead chip.

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity's impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction.Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources.

The effects of mobile phone addiction on bedtime procrastination in university students: the masking effect of physical activity and anxiety.

PURPOSE: Good sleep is one of the necessary conditions to ensure the normal performance of the physiological and psychological functions of college students. This study aimed to explore the relationship between mobile phone addiction and bedtime procrastination among Chinese college students and the mediating mechanisms of physical exercise and anxiety between the two, with a view to seek ways to prevent and intervene in college students' sleep procrastination and improve their sleep quality. METHODS: Using SPSS 29.0 analysis with Bootstrap's method, 3,800 first-year students, sophomores, and juniors were given the Mobile Phone Addiction Tendency Scale, Bedtime Procrastination Scale, Physical Activity Scale, and Anxiety Scale. The results of the analyses included mediation tests and effect analyses of anxiety and physical activity. RESULTS: The correlation analysis revealed significant positive correlations between mobile phone addiction and bedtime procrastination (r = 0.149, p < 0.01) as well as anxiety (r = 0.497, p < 0.01). Additionally, there was a significant negative correlation between mobile phone addiction and physical activity (r = -0.447, p < 0.01). Physical activity was also found to have significant negative correlations with anxiety (r = -0.506, p < 0.01) and bedtime procrastination (r = -0.424, p < 0.01). Furthermore, anxiety showed a significant positive correlation with bedtime procrastination (r = 0.334, p < 0.01). Physical activity and anxiety acted as substantial mediators between mobile phone addiction and nighttime procrastination. Both mediators had considerable masking effects, with the mediating effect amounting to 50.3% and 25.1%, respectively. Physical exercise and anxiety played a chain mediating role between mobile phone addiction and bedtime procrastination, and the masking effect was also significant, with a mediating effect size of 13.4%. CONCLUSIONS: This study reveals the special characteristics of the influencing factors and pathways of bedtime procrastination in this group of college students, providing targeted evidence for the prevention and intervention of bedtime procrastination in college students. It also has an important reference value for the effects of exercise and comprehensive intervention to improve bedtime procrastination and enhance the quality of sleep in college students.

Development of an admission criterion framework for high-cost medical consumables in governmental hospitals: a systematic review.

BACKGROUND: High-cost medical consumables (HMCs) have emerged as significant economic and technological challenges for numerous national healthcare systems. Governmental hospitals play an indispensable role in many national health systems, closely linked to the evaluation of admissions and the management of procurement for HMCs. Nevertheless, many governmental hospitals face avoidable management risks due to the lack of a decision-making tool. In response, we conducted a systematic review to establishing a framework for the admission criteria of HMCs. This framework aims to enhance their effective utilization and maximize economic, clinical, and social benefits. METHODS: In accordance with a systematic review protocol developed for our study, we conducted comprehensive searches in the PubMed, Web of Science, and Embase databases to identify all correlation studies conducted prior to December 31, 2021. Subsequently, two independent reviewers performed a two-round screening process, resulting in the inclusion of 23 articles in our study. Finally, a third reviewer meticulously examined the selected indicators and contributed to the development of the final criterion framework. RESULTS: The criterion framework was established with 7 first-level indicators and 23 s-level indicators. Among the first-level indicators, "Clinical Benefit" held the highest significance, with a combined weight of 1.606, followed by "Economic Value" and "Organizational Impact" at 1.497 and 1.159, respectively. At the second level, "Safety" and "Efficacy" carried equal weight in the decision-making tool, with combined weights of approximately 1.300 each and a standard combined weight of 0.130. CONCLUSION: This admission criteria framework serves as a vital decision-making tool for managing admissions and highlights several crucial evaluation indicators. Economic considerations emerge as the principal determinant in HMCs procurement decisions. Consequently, healthcare managers and decision-makers are recommended to give precedence to value-based healthcare and evidence-based procurement practices. In the long term, governmental hospitals must grapple with the challenge of judiciously allocating limited resources to maximize both social and economic benefits.

Network meta-analysis of the effectiveness of different interventions for internet addiction in college students.

BACKGROUND: Internet addiction jeopardizes teenagers' physical and mental health, as well as their academic performance, and causes a variety of cognitive dysfunctions and psychological and mental health illnesses, among other things. It is a huge issue that families, schools, and society must address immediately. OBJECTIVES: This study used network meta-analysis to evaluate the impact of several interventions on college students' Internet addiction. The goal was to identify the most effective interventions and establish a reference for future interventions. We systematically searched relevant literature in domestic and international databases such as Web of Science, PubMed, EMBASE, Cochrane Library, Pro Quest, China Knowledge, Wan fang, Wipo, etc. We assessed the risk of bias according to the revised Cochrane Randomized Trials Risk of Bias Tool (RoB2) and used R Studio Software and Stata 14.0 for traditional meta-analysis and network meta-analysis. A network meta-analysis based on the IAT scale showed that comprehensive interventions had the highest probability of being the best intervention for IA (SUCRA = 90.6 % based on IAT); focused solution short-term therapy had the highest probability of being the best intervention for IA based on the CIAS-R (19 White Feather) scale (SUCRA = 100 %). CONCLUSIONS: The majority of interventions have a significant influence on the treatment of IA, and improvements in Internet addiction symptoms are more noticeable when a combination of interventions is used rather than just one.

Multiphase enhanced CT-based transformer for differential diagnosis and predicting surgical risk events of solid abdominal tumors in children.

BACKGROUND: For pediatric patients with solid abdominal tumors, early diagnosis can guide clinical treatment decisions, and comprehensive preoperative evaluation is essential to reduce surgical risk. The aim of this study was to explore the feasibility of multiphase enhanced CT-based transformer in the early diagnosis of tumors and prediction of surgical risk events (SRE). METHODS: A total of 496 pediatric patients with solid abdominal tumors were enrolled in the study. With Swin transformer, we constructed and trained two Swin-T models based on preoperative multiphase enhanced CT for personalized prediction of tumor type and SRE status. Subsequently, we comprehensively evaluated the performance of each model and constructed four benchmark models for performance comparison. RESULTS: There was no significant difference in SRE status between tumor types. In the diagnostic task, areas under the receiver operating characteristic curves (AUC) of the Swin-T model were 0.987 (95 % CI, 0.973-0.997) and 0.844 (95 % CI, 0.730-0.940) in the training and validation cohorts, respectively. In predicting SRE, AUCs of the Swin-T model were 0.920 (95 % CI, 0.885-0.948) and 0.741 (95 % CI, 0.632-0.838) in the training and test cohorts, respectively. The Swin-T model achieved the best performance in both classification tasks compared to benchmark models. CONCLUSION: The Swin-T model is a promising tool to assist pediatricians in the differential diagnosis of abdominal tumors and in comprehensive preoperative evaluation.

The causal relationship between gut microbiota and lymphoma: a two-sample Mendelian randomization study.

Background: Previous studies have indicated a potential link between the gut microbiota and lymphoma. However, the exact causal interplay between the two remains an area of ambiguity. Methods: We performed a two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between gut microbiota and five types of lymphoma. The research drew upon microbiome data from a research project of 14,306 participants and lymphoma data encompassing 324,650 cases. Single-nucleotide polymorphisms were meticulously chosen as instrumental variables according to multiple stringent criteria. Five MR methodologies, including the inverse variance weighted approach, were utilized to assess the direct causal impact between the microbial exposures and lymphoma outcomes. Moreover, sensitivity analyses were carried out to robustly scrutinize and validate the potential presence of heterogeneity and pleiotropy, thereby ensuring the reliability and accuracy. Results: We discerned 38 potential causal associations linking genetic predispositions within the gut microbiome to the development of lymphoma. A few of the more significant results are as follows: Genus Coprobacter (OR = 0.619, 95% CI 0.438-0.873, P = 0.006) demonstrated a potentially protective effect against Hodgkin's lymphoma (HL). Genus Alistipes (OR = 0.473, 95% CI 0.278-0.807, P = 0.006) was a protective factor for diffuse large B-cell lymphoma. Genus Ruminococcaceae (OR = 0.541, 95% CI 0.341-0.857, P = 0.009) exhibited suggestive protective effects against follicular lymphoma. Genus LachnospiraceaeUCG001 (OR = 0.354, 95% CI 0.198-0.631, P = 0.0004) showed protective properties against T/NK cell lymphoma. The Q test indicated an absence of heterogeneity, and the MR-Egger test did not show significant horizontal polytropy. Furthermore, the leave-one-out analysis failed to identify any SNP that exerted a substantial influence on the overall results. Conclusion: Our study elucidates a definitive causal link between gut microbiota and lymphoma development, pinpointing specific microbial taxa with potential causative roles in lymphomagenesis, as well as identifying probiotic candidates that may impact disease progression, which provide new ideas for possible therapeutic approaches to lymphoma and clues to the pathogenesis of lymphoma.

Efficacy and safety of selumetinib in patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas: a systematic review and meta-analysis.

BACKGROUND: The approval of selumetinib in patients with neurofibromatosis type 1(NF1) and inoperable plexiform neurofibromas (PN) has reshaped the landscape of clinical management of the disease, and further comprehensive evaluation of the drug's efficacy and safety is needed. METHODS: Original articles reporting on the efficacy and safety of elumetinib in patients with NF1 were comprehensively searched in the Pubmed database, Embase database, Cochrane Library, and Web of Science database and screened for inclusion of studies that met the criteria. We pooled the objective response rate (ORR), disease control rate (DCR), disease progression rate (DPR), and the rate of improvement in PN-related complications using meta-analysis. The incidence of drug-related adverse events was also statistically analyzed. RESULTS: This study included 10 clinical trials involving 268 patients. The pooled ORR was 68.0% (95% CI 58.0-77.3%), the DCR was 96.8% (95% CI 90.8-99.7%) and the DPR was only 1.4% (95% CI 0-4.3%). The pooled improvement rate was 75.3% (95% CI 56.2-90.9%) for pain and 77.8% (95% CI 63.1-92.5%) for motor disorders. Most adverse events were mild, with the most common being gastrointestinal reactions (diarrhea: 62.5%; vomiting: 54.5%). CONCLUSION: Our study demonstrates that selumetinib is effective in patients with NF1 and PN, significantly improving the serious complications associated with PN as well as having tolerable toxicities. Our findings help to increase clinicians' confidence in applying selumetinib and promote the clinical adoption and benefit of the new drug.

Immunomodulatory multicellular scaffolds for tendon-to-bone regeneration.

Limited motor activity due to the loss of natural structure impedes recovery in patients suffering from tendon-to-bone injury. Conventional biomaterials focus on strengthening the regenerative ability of tendons/bones to restore natural structure. However, owing to ignoring the immune environment and lack of multi-tissue regenerative function, satisfactory outcomes remain elusive. Here, combined manganese silicate (MS) nanoparticles with tendon/bone-related cells, the immunomodulatory multicellular scaffolds were fabricated for integrated regeneration of tendon-to-bone. Notably, by integrating biomimetic cellular distribution and MS nanoparticles, the multicellular scaffolds exhibited diverse bioactivities. Moreover, MS nanoparticles enhanced the specific differentiation of multicellular scaffolds via regulating macrophages, which was mainly attributed to the secretion of PGE2 in macrophages induced by Mn ions. Furthermore, three animal results indicated that the scaffolds achieved immunomodulation, integrated regeneration, and function recovery at tendon-to-bone interfaces. Thus, the multicellular scaffolds based on inorganic biomaterials offer an innovative concept for immunomodulation and integrated regeneration of soft/hard tissue interfaces.

Construction of methylation driver gene-related prognostic signature and development of a new prognostic stratification strategy in neuroblastoma.

BACKGROUND: Aberrant DNA methylation is one of the major epigenetic alterations in neuroblastoma. OBJECTIVE: Exploring the prognostic significance of methylation driver genes in neuroblastoma could help to comprehensively assess patient prognosis. METHODS: After identifying methylation driver genes (MDGs), we used the LASSO algorithm and stepwise Cox regression to construct methylation driver gene-related risk score (MDGRS), and evaluated its predictive performance by multiple methods. By combining risk grouping and MDGRS grouping, we developed a new prognostic stratification strategy and explored the intrinsic differences between the different groupings. RESULTS: We identified 44 stably expressed MDGs in neuroblastoma. MDGRS showed superior predictive performance in both internal and external cohorts and was strongly correlated with immune-related scores. MDGRS can be an independent prognostic factor for neuroblastoma, and we constructed the nomogram to facilitate clinical application. Based on the new prognostic stratification strategy, we divided the patients into three groups and found significant differences in overall prognosis, clinical characteristics, and immune infiltration between the different subgroups. CONCLUSION: MDGRS was an accurate and promising tool to facilitate comprehensive pre-treatment assessment. And the new prognostic stratification strategy could be helpful for clinical decision making.

Effect of Mobile Phone Addiction on Physical Exercise in University Students: Moderating Effect of Peer Relationships.

OBJECTIVE: The influence of mobile phone addiction (MPA) on physical exercise in university students was explored, and peer relationships were introduced as a moderating variable. METHODS: A cross-sectional study design was adopted, and an online survey questionnaire was conducted to investigate two universities in Nantong City, Jiangsu Province, and Chongzuo City, Guangxi Zhuang Autonomous Region. A total of 4959 university students completed the questionnaire. Measurement tools included the Mobile Phone Addiction Tendency Scale, the Physical Activity Rating Scale, and the Peer Rating Scale of university students. RESULTS: University students scored 39.322 ± 15.139 for MPA and 44.022 ± 7.735 for peer relationships, with 87.8% of their physical exercise, in terms of exercise grade, being classified as medium or low intensity. The MPA of the university students was negatively correlated with peer relationships (r = -0.377, p < 0.001) and physical exercise behavior (r = -0.279, p < 0.001). The moderating effect of peer relationships on the MPA-physical exercise behavior relationship was significant (ΔR2 = 0.03, p < 0.001). CONCLUSIONS: The physical exercise of university students was at a medium or low intensity. The more serious the university students' addiction to mobile phones was, the lower the amount of physical exercise. The physical activity of males was higher than that of females. MPA and peer relationships were the limiting factors of the physical exercise behavior of university students. Under the lower effect of peer relationship regulation, MPA had a greater negative impact on physical exercise behavior. The data from this research can provide theoretical support to improve the participation of university students in physical activities.

Combining multiple cell death pathway-related risk scores to develop neuroblastoma cell death signature.

PURPOSE: Cell death plays an important role in tumourigenesis and progression; nevertheless, the clinical significance of cell death-related genes in neuroblastoma remains incompletely understood. METHODS: We separately constructed the corresponding risk scores for each of the eight cell death pathways separately and assessed their predictive performance. Through Cox regression analysis, these eight risk scores were integrated to obtain final cell death risk scores (CDRS). We evaluated the predictive performance of CDRS in multiple datasets and compared its accuracy with the clinical characteristics of patients and some existing prognostic models for neuroblastoma. We then explored the differences in immune infiltration between the high and low CDRS groups, and the significance of CDRS on EFS and disease progression. RESULTS: All eight risk scores have high predictive accuracy, with the Immunogenic-RS being the most accurate and the cuproptosis-RS the least accurate. Model genes are mainly enriched in a variety of cancer-related pathways and are closely related to the clinical characteristics. CDRS showed superior and robust predictive performance in multiple datasets and was more accurate than the clinical characteristics of patients and some existing prognostic models for neuroblastoma. High CDRS group featured distinct immune cold tumor profiles and may have poorer immune checkpoint inhibitor efficacy. CDRS had significance in predicting EFS and disease progression. CONCLUSION: We integrated risk scores associated with multiple cell death pathways to develop a high-performing and robust neuroblastoma signature. CDRS was a promising tool that may help with risk assessment and prediction of overall prognosis, and thus improve clinical outcomes.

[Efficacy and safety of rituximab in children and adolescents with mature B-cell non-Hodgkin's lymphoma: a Meta analysis]. / 利妥昔单抗治疗儿童及青少年成熟Bç»†èƒžéžéœå¥‡é‡‘æ·‹å·´ç˜¤ç–—æ•ˆåŠå®‰å ¨æ€§çš„Meta分析.

OBJECTIVES: To study the efficacy and safety of rituximab combined with chemotherapy in the treatment of children and adolescents with mature B-cell non-Hodgkin's lymphoma (B-NHL) through a Meta analysis. METHODS: The databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and Weipu were searched to obtain 10 articles on rituximab in the treatment of mature B-NHL in children and adolescents published up to June 2022, with 886 children in total. With 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate, complete remission rate, mortality rate, and incidence rate of adverse reactions as outcome measures, RevMan 5.4 software was used for Meta analysis, subgroup analysis, sensitivity analysis, and publication bias analysis. RESULTS: The rituximab+chemotherapy group showed significant increases in the 3-year EFS rate (HR=0.38, 95%CI: 0.25-0.59, P<0.001), 3-year OS rate (HR=0.29, 95%CI: 0.14-0.61, P=0.001), and complete remission rate (OR=3.72, 95%CI: 1.89-7.33, P<0.001) as well as a significant reduction in the mortality rate (OR=0.31, 95%CI: 0.17-0.57, P<0.001), as compared with the chemotherapy group without rituximab. There was no significant difference in the incidence rate of adverse reactions between the two groups (OR=1.28, 95%CI: 0.85-1.92, P=0.24). CONCLUSIONS: The addition of rituximab to the treatment regimen for children and adolescents with mature B-cell non-Hodgkin's lymphoma can bring significant survival benefits without increasing the incidence of adverse reactions.

Effect of thermal process on the key aroma components of green tea with chestnut-like aroma.

BACKGROUND: Chestnut-like aroma is one of the unique qualities of Chinese green tea and has become an important factor influencing consumer decisions. However, the chemical formation mechanism of chestnut-like aroma during green tea processing remains unclear. In this study, the dynamic changes of key components contributing to chestnut-like aroma and their precursors were analyzed in fresh leaves, fixation leaves, first baking tea leaves, and green tea. RESULTS: The thermal process had an important effect on volatile components in tea leaves, causing a significant decrease of alcohols and esters and a significant increase of ketones, acids, phenols, and sulfur compounds. Furthermore, 31 volatiles were identified as the key odorants responsible for chestnut-like aroma of green tea, including dimethyl sulfide, methyl isobutenyl ketone, 2-methylbutanal, 2,4-dimethylstyrene, d-limonene, methyl 2-methylvalerate, linalool, decanal, longifolene, phenylethyl alcohol, l-α-terpineol, jasmone, and so on. And the majority of these odorants were only formed in the drying stage. Additionally, isoleucine, theanine, methionine, and glucose were found to be involved in the formation of chestnut-like aroma of green tea. CONCLUSION: The drying process played a vital important role in the formation of chestnut-like aroma of green tea. © 2022 Society of Chemical Industry.

Current Status and Correlation of Physical Activity and Tendency to Problematic Mobile Phone Use in College Students.

OBJECTIVE: To explore the effect of problematic mobile phone use on college students' physical activity and their relationships. METHODS: A cross-sectional study was conducted among 3980 college students from three universities in Jiangsu province by random cluster sampling. The International Physical Activity Questionnaire Short (IPAQ-SF) measured college students' physical activity. The Mobile Phone Addiction Tendency Scale for College Students (MPATS) measured problematic mobile phone use tendencies. College students' physical activity was measured by the International Physical Activity Questionnaire Short (IPAQ-SF), and the Mobile Phone Addiction Tendency Scale measured their mobile phone addiction tendency for College Students (MPATS). RESULTS: (1) The proportions of the low-, medium-, and high-intensity physical activity were 83.5%, 10.7%, and 5.8%, respectively, with gender differences; The score of problematic mobile phone use tendency was 38.725 ± 15.139. (2) There were significant differences in problematic mobile phone use tendency among college students with different physical activity intensity (F = 11.839, p < 0.001, η2 = 0.007). (3) The level of physical activity was significantly correlated with the tendency of problematic mobile phone use (r = -0.173, p < 0.001). (4) Physical activity of college students could significantly predict the tendency of problematic mobile phone use (F (3,3605) = 11.296, p < 0.001). CONCLUSIONS: The physical activity of college students was mainly moderate to low intensity, while the tendency of problematic mobile phone use was high. College students' physical activity level was one of the important constraints of problematic mobile phone use tendency.

Chinese college students COVID-19 phobia and negative moods: Moderating effects of physical exercise behavior.

Objective: We investigated the effects of COVID-19 fear on negative moods among college students, and assessed the efficacy of physical exercise behavior as a moderator variable. Methods: This was a cross-sectional study. Students from three colleges and universities in Shangqiu City, Henan Province and Yangzhou City, Jiangsu Province were enrolled in this study, which was performed during the COVID-19 pandemic using an online questionnaire. A total of 3,133 college students completed the questionnaire. Measurement tools included the COVID-19 Phobia Scale (C19P-S), Depression-Anxiety-Stress Self-Rating Scale (DASS), and the Physical Activity Behavior Scale (PARS-3). Results: During the COVID-19 pandemic, the rates of depression, anxiety, and stressful negative moods among college students were 35.5, 65.5, and 10.95%, respectively; there was a positive correlation between COVID-19 fear and negative moods among college students (r = 0.479, p < 0.001), which was negatively correlated with physical exercise behavior (r = -0.4, p < 0.001); the regulating effects of physical exercise behavior were significant (ΔR2 = 0.04, p < 0.001). Conclusion: The rate of negative moods among college students is high, and the fear for COVID-19 is one of the key factors that lead to negative moods. Physical exercise can modulate the impact of COVID-19 fear among college students on negative moods. Studies should elucidate on mental health issues among different populations during the COVID-19 pandemic.

Identification of Key Genes Associated with Risk and Prognosis of Neuroblastoma.

Neuroblastoma is a childhood malignancy with high morbidity and mortality. We identified key biomarkers associated with neuroblastoma risk and prognosis. The gene modules most associated with neuroblastoma risk were derived by WGCNA. Modular genes were intersected with differentially expressed genes between patients with high-risk (HR) and non-high-risk (NHR) to obtain risk genes, and enrichment analysis was performed. After incorporating risk genes into Cox regression analysis, LASSO algorithm, and K-M survival analysis, key genes were identified and introduced into four external datasets for validation. We performed short time-series expression miner analysis and single-sample genome enrichment analysis. Finally, we evaluated the difference in DNA methylation levels to identify meaningful methylation marks. We identified 5 key genes (ANO6, CPNE2, DST, PLXNC1, SCN3A) for neuroblastoma risk and prognosis, which correlated closely with known neuroblastoma biomarkers. All key genes showed a progressive downregulation trend with increasing risk levels of neuroblastoma. The immune infiltration of 14 immune cells was significantly different between HR-NB and NHR-NB, and most immune cells were negatively correlated with key genes. Furthermore, the expression of ANO6, CPNE2, DST, and PLXNC1 was modified by DNA methylation. This study identified 5 key genes for neuroblastoma risk and prognosis that were potential biomarkers.

Safety, tolerability and pharmacokinetics of a Class I natural medicine with therapeutic potential for vascular dementia: Naoqingzhiming tablet.

Naoqingzhiming, whose active ingredient is echinacoside, is the first new Class I natural medicine approved for clinical trials for the therapeutic potential of vascular dementia in China. We report randomized, double-blind, placebo-controlled trials to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of Naoqingzhiming tablet after oral administration in healthy Chinese subjects. The single ascending dose of Naoqingzhiming tablet (180-2160 mg) were well tolerated in all enrolled subjects, without serious adverse events and adverse events leading to withdrawal from the study. The most common drug-related treatment-emergent adverse events were elevated blood bilirubin and serum uric acid. No clinically significant findings were found in the physical examinations, vital signs or electrocardiograms. After single-dose administration of Naoqingzhiming tablet, echinacoside was absorbed with a Tmax at 1.25-1.75 h and declined with a t1/2 of 2.42-3.33 h. However, the proportionality coefficients for Cmax, AUC0-t and AUC0-∞ of echinacoside were not fully contained in the pre-defined 90 % CI criterion (0.91-1.09). As a result, the dose proportionality could not be concluded statistically within the dosage range of this study. Overall, the safety profile and PK properties support further development and use of Naoqingzhiming in vascular dementia.

Nanoarchitectured prototypes of mesoporous silica nanoparticles for innovative biomedical applications.

Despite exceptional morphological and physicochemical attributes, mesoporous silica nanoparticles (MSNs) are often employed as carriers or vectors. Moreover, these conventional MSNs often suffer from various limitations in biomedicine, such as reduced drug encapsulation efficacy, deprived compatibility, and poor degradability, resulting in poor therapeutic outcomes. To address these limitations, several modifications have been corroborated to fabricating hierarchically-engineered MSNs in terms of tuning the pore sizes, modifying the surfaces, and engineering of siliceous networks. Interestingly, the further advancements of engineered MSNs lead to the generation of highly complex and nature-mimicking structures, such as Janus-type, multi-podal, and flower-like architectures, as well as streamlined tadpole-like nanomotors. In this review, we present explicit discussions relevant to these advanced hierarchical architectures in different fields of biomedicine, including drug delivery, bioimaging, tissue engineering, and miscellaneous applications, such as photoluminescence, artificial enzymes, peptide enrichment, DNA detection, and biosensing, among others. Initially, we give a brief overview of diverse, innovative stimuli-responsive (pH, light, ultrasound, and thermos)- and targeted drug delivery strategies, along with discussions on recent advancements in cancer immune therapy and applicability of advanced MSNs in other ailments related to cardiac, vascular, and nervous systems, as well as diabetes. Then, we provide initiatives taken so far in clinical translation of various silica-based materials and their scope towards clinical translation. Finally, we summarize the review with interesting perspectives on lessons learned in exploring the biomedical applications of advanced MSNs and further requirements to be explored.

Exploring spatiotemporal variation characteristics of China's industrial carbon emissions on the basis of multi-source data.

Spatiotemporal variations of industrial carbon emissions (IE) must be scientifically understood, which will be helpful to formulate reasonable emission reduction strategies. Given that spatial distribution of IE is irrelevant to space agents commonly used (such as population and nighttime light), estimation and spatialization methods for total carbon dioxide (CO2) emissions are not entirely suitable for IE. Therefore, this paper used greenhouse gases observing satellite level 4A product to estimate IE at the city level and used industrial land density to obtain the distribution of IE within the administrative districts. Sectoral emission inventories of 182 cities and a mosaic Asian anthropogenic emission inventory named MIX were used to verify the results. Then, spatiotemporal variation characteristics of China's IE were analyzed from multiple levels. Results showed that (1) the mean relative error of estimation results was 56.11%, among which 62 cities had relative error of less than 30%. Gridded IE in this paper had high consistency with MIX. (2) Cities with high IE experienced rapid growth from 2009 to 2012, followed by slower growth from 2012 to 2017. (3) Centroid of significant cold and hot spots moved to the southeast and northwest, respectively. Most cities with high annual IE growth had relatively low emission efficiency, mainly located in Inner Mongolia and Xinjiang. Aggregation of medium and high IE grids may represent high emission efficiency. Significant differences still exist between cities in IE, and sustainable development strategies should be formulated according to local conditions. Regions with high annual growth or low emission efficiency are the key to achieving IE reduction targets in future.

Comprehensive Analysis of Metabolic Fluxes from Leucoanthocyanins to Anthocyanins and Proanthocyanidins (PAs).

Anthocyanins and PAs are the two most common flavonoids, which are widely present among diverse species. Great progress has been made in their synthesis and regulation. In this study, we analyzed the metabolic fluxes from their synthetic precursor leucoanthocyanins, which were obtained by overexpression of dihydroflavonol 4-reductase (DFR) in vitro and in vivo. The unstable product leucocyanidin generated in the CsDFRa enzymatic reaction was easily converted into C-type carbocations under weak acidic conditions, which could be further involved in the synthesis of C-type PAs in vitro. Additionally, the metabolites in tobacco overexpressing CsDFRa and Arabidopsis thaliana DFR and anthocyanidin synthase (ANS) mutants were investigated. In CsDFRa transgenic tobacco, the content of anthocyanins in the petals was greatly increased, but no catechin or PA was detected. In A. thaliana, EC-type carbocation was mainly accumulated in the wild type (WT), and the C-type carbocation was only detected in the ans mutant. In tea plant, the accumulation of C-type PAs is strong positively correlated with the expression of CsDFRa. In summary, leucocyanidin is not only involved in the synthesis of downstream anthocyanin and epicatechin but also can be converted into C-type carbocation to participate in the synthesis of C-type PAs. Hence, from leucocyanidin, three metabolic fluxes were formed toward catechin, cyanidin, and C-type carbocation. These results enriched the metabolic fluxes of leucoanthocyanins and further elaborated the roles of DFR in the process of C-type PA formation.