Efficient and scalable synthesis of 3,4-dihydroisoquinolin-1(2H)-ones by benzylic oxidation of tetrahydroisoquinoline derivatives using cerium ammonium nitrate (CAN).

An efficient and scalable method for the synthesis of 3,4-dihydroisoquinolin-1(2H)-ones through benzylic oxidation of tetrahydroisoquinoline derivatives using a catalytic amount of cerium ammonium nitrate (CAN) and a stoichiometric amount of NaBrO3 as oxidants was developed. The reaction is significantly influenced by the substituent groups on the phenyl ring. While electron-withdrawing groups on the phenyl ring can lower the reactivities of the substrates, electron-donating groups on the phenyl ring can dramatically promote the oxidation rate.

Synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines and isocoumarins enabled by multi-component reagents system (MCRS).

The combining use of BnSCF2D, mCPBA and Tf2O serves as an efficient multi-component reagents system (MCRS) for the synthesis of deuteriodifluoromethylthiolated isocoumarins-1-imines/isocoumarins via intramolecular cyclization/deuteriodifluoromethylthiolation of 2-alkynylbenzamides/2-alkynylbenzoates. The approach features the generation of the crucial reactive electrophilic sulfonium salt through a sequence process involving the oxidation of BnSCF2D by mCPBA followed by Tf2O promoted activation.

Small molecule-inducible and photoactivatable cellular RNA N1-methyladenosine editing.

N1-methyladenosine (m1A) modification is one of the most prevalent epigenetic modifications on RNA. Given the vital role of m1A modification in RNA processing such as splicing, stability and translation, developing a precise and controllable m1A editing tool is pivotal for in-depth investigating the biological functions of m1A. In this study, we developed an abscisic acid (ABA)-inducible and reversible m1A demethylation tool (termed AI-dm1A), which targets specific transcripts by combining the chemical proximity-induction techniques with the CRISPR/dCas13b system and ALKBH3. We successfully employed AI-dm1A to selectively demethylate the m1A modifications at MALAT1 A8422, and this demethylation process could be reversed by removing ABA. Furthermore, we validated its demethylating function on various types of cellular RNAs including mRNA, rRNA and lncRNA. Additionally, we used AI-dm1A to specifically demethylate m1A on ATP5D mRNA, which promoted ATP5D expression and enhanced the glycolysis activity of tumor cells. Conversely, by replacing the demethylase ALKBH3 with methyltransferase TRMT61A, we also developed a controllable m1A methylation tool, namely AI-m1A. Finally, we caged ABA by 4,5-dimethoxy-2-nitrobenzyl (DMNB) to achieve light-inducible m1A methylation or demethylation on specific transcripts. Collectively, our m1A editing tool enables us to flexibly study how m1A modifications on specific transcript influence biological functions and phenotypes.

Construction of Cobalt Porphyrin-Modified Cu2 O Nanowire Array as a Tandem Electrocatalyst for Enhanced CO2 Reduction to C2 Products.

Here, the molecule-modified Cu-based array is first constructed as the self-supporting tandem catalyst for electrocatalytic CO2 reduction reaction (CO2 RR) to C2 products. The modification of cuprous oxide nanowire array on copper mesh (Cu2 O@CM) with cobalt(II) tetraphenylporphyrin (CoTPP) molecules is achieved via a simple liquid phase method. The systematical characterizations confirm that the formation of axial coordinated Co-O-Cu bond between Cu2 O and CoTPP can significantly promote the dispersion of CoTPP molecules on Cu2 O and the electrical properties of CoTPP-Cu2 O@CM heterojunction array. Consequently, as compared to Cu2 O@CM array, the optimized CoTPP-Cu2 O@CM sample as electrocatalyst can realize the 2.08-fold C2 Faraday efficiency (73.2% vs 35.2%) and the 2.54-fold current density (-52.9 vs -20.8 mA cm-2 ) at -1.1 V versus RHE in an H-cell. The comprehensive performance is superior to most of the reported Cu-based materials in the H-cell. Further study reveals that the CoTPP adsorption on Cu2 O can restrain the hydrogen evolution reaction, improve the coverage of * CO intermediate, and maintain the existence of Cu(I) at low potential.

Multi-omics comprehensive analysis reveals the predictive value of N6-methyladenosine- related genes in prognosis and immune escape of bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) is the most frequent RNA modification in mammals, and its role in bladder cancer (BC) remains rarely revealed. OBJECTIVE: To predict the value of m6A-related genes in prognosis and immunity in BC. METHODS: We performed multiple omics analysis of 618 TCGA and GEO patients and used principal component analysis (PCA) to calculate the m6A score for BC patients. RESULTS: We described the multiple omics status of 23 m6A methylation-related genes (MRGs), and four m6A clusters were identified, which showed significant differences in immune infiltration and biological pathways. Next, we intersected the differential genes among m6A clusters, and 11 survival-related genes were identified, which were used to calculate the m6A score for the patients. We found that the high-score (HS) group showed lower tumor mutation burden (TMB) and TP53 mutations and better prognosis than the low-score (LS) group. Lower immune infiltration, higher expression of PD-L1, PD-1, and CTLA4, and higher immune dysfunction and immune exclusion scores were identified in the LS group, suggesting a higher possibility of immune escape. Finally, the experimental verification shows that the m6A related genes, such as IGFBP1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These findings revealed the important roles of m6A MRGs in predicting prognosis, TMB status, TP53 mutation, immune functions and immunotherapeutic response in BC.

Formation of Different Polyploids Through Disrupting Meiotic Crossover Frequencies Based on cntd1 Knockout in Zebrafish.

Polyploidy, a significant catalyst for speciation and evolutionary processes in both plant and animal kingdoms, has been recognized for a long time. However, the exact molecular mechanism that leads to polyploid formation, especially in vertebrates, is not fully understood. Our study aimed to elucidate this phenomenon using the zebrafish model. We successfully achieved an effective knockout of the cyclin N-terminal domain containing 1 (cntd1) using CRISPR/Cas9 technology. This resulted in impaired formation of meiotic crossovers, leading to cell-cycle arrest during meiotic metaphase and triggering apoptosis of spermatocytes in the testes. Despite these defects, the mutant (cntd1-/-) males were still able to produce a limited amount of sperm with normal ploidy and function. Interestingly, in the mutant females, it was the ploidy not the capacity of egg production that was altered. This resulted in the production of haploid, aneuploid, and unreduced gametes. This alteration enabled us to successfully obtain triploid and tetraploid zebrafish from cntd1-/- and cntd1-/-/- females, respectively. Furthermore, the tetraploid-heterozygous zebrafish produced reduced-diploid gametes and yielded all-triploid or all-tetraploid offspring when crossed with wild-type (WT) or tetraploid zebrafish, respectively. Collectively, our findings provide direct evidence supporting the crucial role of meiotic crossover defects in the process of polyploidization. This is particularly evident in the generation of unreduced eggs in fish and, potentially, other vertebrate species.

JAM3: A prognostic biomarker for bladder cancer via epithelial­mesenchymal transition regulation

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial­mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-Cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.

Effects of functional correction training on movement patterns and physical fitness in male college students.

The objective of this study is to investigate the effects of functional corrective training and static stretching on the quality of movement patterns and physical fitness in college students. The study was conducted with 30 male college students from a university in Guangzhou, China. The participants were randomly assigned to either the functional corrective training group (FCT, n = 15, age = 20.93 ± 0.85, BMI = 22.07 ± 2.33) or the static stretching group (SS, n = 13, age = 20.85 ± 0.86, BMI = 21.98 ± 1.80). Two participants from the SS group dropped out due to personal reasons, leaving 13 subjects in that group. Both groups underwent a 6-week training intervention, with sessions held twice a week. The FCT group participated in flexibility training, and/or static motor control training, and/or dynamic motor control training for 10-15 min. The SS group performed static stretching exercises targeting five specific muscles, with 30 s per side and two sets. The Functional Movement Screen (FMS), body composition, sit-and-reach, standing long jump, and pull-ups were assessed before and after the intervention. Differences in FMS outcomes were analyzed using two samples of the Mann-Whitney U test. Physical fitness outcomes were analyzed using a repeated measures analysis of variance (ANOVA) with a 2 (group) × 2 (time) design. After 6 weeks of intervention, the FCT group showed statistically significant improvements in the hurdle step (Z = -2.449, p = 0.014), inline lunge (Z = -2.000, p = 0.046), rotary stability (Z = -2.309, p = 0.021), and composite scores (Z = -3.316, p = 0.001). Comparisons between groups indicated that BMI (FCT, ES = 0.04; SS, ES = -0.11), 30-m sprint (FCT, ES = 0.12; SS, ES = 0.28), body fat percentage (BF%) (FCT, ES = -0.25; SS, ES = -0.07), and sit-and-reach (FCT, ES = 0.17; SS, ES = 0.06) were not statistically significant in both the pre- and post-tests. The effect sizes of all physical fitness indicators were greater in the FCT group than in the SS group. The FCT, consisting of two sessions per week for 6 weeks, has been proven to be effective in improving the quality of movement patterns by improved stability and advanced movements. However, the improvements in physical fitness did not reach statistical significance. FMS and FCT are generally affordable and accessible for college students. College students have the opportunity to employ the FMS tool to assess potential injury risks and address them, thereby reducing the risk of injuries.

Multi-Functional Formaldehyde-Nitrate Batteries for Wastewater Refining, Electricity Generation, and Production of Ammonia and Formate.

As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75 V, a peak power density of 3.38 mW cm-2 and the yield rates of 32.7 mg h-1 cm-2 for ammonia and 889.4 mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25 cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03 W⋅h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.

Application of a New Monitoring Variable: Effects of Power Loss During Squat Training on Strength Gains and Sports Performance.

ABSTRACT: Zhang, M, Chen, L, Dai, J, Yang, Q, Huang, Z, He, J, Ji, H, Sun, J, and Li, D. Application of a new monitoring variable: Effects of power loss during squat training on strength gains and sports performance. J Strength Cond Res 38(4): 656-670, 2024-This study aimed to compare the effects of power loss (PL) autoregulated volume (PL10 and PL20) with standardized fixed-load (FL) prescription on strength, sports performance, and lean body mass (LBM). Thirty-five female basketball players from a sports college were randomly assigned to 3 experimental groups (PL10, n = 12; PL20, n = 12; and FL, n = 11, respectively) that performed a resistance training (RT) program with wave-like periodization for 10 weeks using the back squat exercise. Assessments performed before (Pre) and after (Post) intervention included assessed 1 repetition maximum (1RM), body composition, 20-m sprint (T20M), change of direction (COD), and jump performance, including countermovement jump with arm swing, maximum vertical jump, and reactive strength index. Three groups showed significant improvements in strength (effect size [ES]: PL10 = 2.98, PL20 = 3.14, and FL = 1.90; p < 0.001) and jump performance (ES: PL10 = 0.74, PL20 = 1.50, and FL = 0.50; p <0.05-0.001). However, PL10 and PL20 demonstrated different advantages in sports performance compared with FL (group × time interaction, p <0.05). Specifically, PL10 significantly improved COD performance (ES = -0.79 ∼ -0.53, p <0.01), whereas PL20 showed greater improvements in sprint (ES = -0.57, p <0.05) and jump performance (ES = 0.67-1.64, p <0.01-0.001). Moreover, PL10 resulted in similar gains to PL20 and beneficial improvements compared with FL in LBM, despite performing the least repetitions. Overall, the study indicates that power loss-based autoregulation induces greater gains in LBM and sports performance, as well as eliciting a higher efficiency dose response than standardized FL prescriptions, particularly for PL10. Therefore, incorporating PL monitoring in training programs is recommended, and further studies on power-based RT would be worthwhile.

Flexible EEG Electrodes with Embedded Pressure Sensors and Customized Interface Towards Comfortable Home EEG Monitoring.

To realize stable and comfortable dry electroencephalography (EEG) recording for home healthcare, a flexible pressure-sensitive electrode (PSE) is proposed, and a dedicated multi-channel pressure sensor interface is developed. The PSE monitors the pressure on the electrode during continuous EEG recording. With the PSE, stable but comfortable electrode-skin contact can be achieved. The analog front-end of the sensor interface is fabricated in 180-nm CMOS, occupying an active area of 0.25 mm2. The flexible sensor exhibited a -2.5 kΩ/kPa sensitivity. The sensor interface enjoyed a large stimulus range of up to 2.65 mApp and showed a resolution of 0.047 - 8.0 mΩ/√Hz. It is digital-compatible, reconfigurable, and area-efficient, which can be migrated into various EEG acquisition integrated circuits and systems.

A new immune-related gene signature predicts the prognosis and immune escape of bladder cancer.

BACKGROUND: The biological roles of immune-related genes (IRGs) in bladder cancer (BC) need to be further elucidated. OBJECTIVE: To elucidate the predictive value of IRGs for prognosis and immune escape in BC. METHODS: We comprehensively analyzed the transcriptomic and clinical information of 430 cases, including 19 normal and 411 BC patients from the TCGA database, and verified 165 BC cases in the GSE13507 dataset. The risk model was constructed based on IRGs by applying LASSO Cox regression and exploring the relationship between the risk score and prognosis, gene mutations, and immune escape in BC patients. RESULTS: We identified 4 survival-related genes (PSMC1, RAC3, ROBO2 and ITGB3) among 6,196 IRGs in both the TCGA and GES13507 datasets,, which were used to establish a gene risk model by applying LASSO Cox regression. The results showed that the high-risk (HR) group was closely associated with poor survival or advanced pathological stage of BC. Furthermore, the risk score was found to be an independent risk factor for prognosis of BC patients. In addition, high-risk individuals showed a greater prevalence of TP53 mutations lower CD8+ T-cell and NK cell infiltration, higher Treg cell infiltration, higher expression of PD-L1, and higher immune exclusion scores than those in the low-risk (LR) group. Finally, the experimental verification shows that the model construction gene, especially PMSC1, plays an important role in the growth and metastasis of bladder cancer. CONCLUSIONS: These evidences revealed the vital role of IRGs in predicting prognosis, TP53 mutation and immune escape in BC patients.

A Five-Channel Weighted Real-Time Algorithm for High-Density Electrodes Spike Sorting.

With the application of high-density neural probes, a neuron can be detected by multiple adjacent probes, and the traditional single-channel spike sorting is no longer suitable. In this paper, we propose a five-channel weighted real-time spike sorting algorithm based on template-matching to process neural signals recorded by high-density probes. This work uses the signals of the center channel and the adjacent four channels to form a five-channel template by weighting, and employs a modified OSort algorithm with unsupervised learning to update the template. We implemented automatic online spike sorting, and tested it with both ground truth recordings and simulated datasets. The experiments show that our algorithm utilizing the information of adjacent channels has a higher sorting accuracy than traditional single-channel spike sorting. The average sorting accuracy reaches 89%, compared to 78% for single-channel.

Maximizing plyometric training for adolescents: a meta-analysis of ground contact frequency and overall intervention time on jumping ability: a systematic review and meta-analysis.

Plyometric training boosts adolescents' jumping ability, crucial for athletic success and health. However, the best total ground contact frequency (TGCF) and overall intervention time (OIT) for these exercises remain unclear. This meta-analysis aims to identify optimal TGCF and OIT in plyometric training for adolescents, focusing on countermovement jump (CMJ) and squat jump (SJ) outcomes. This systematic review encompassed five databases and included 38 studies with 50 randomized controlled experiments and 3347 participants. We used the Cochrane risk assessment tool for study quality and Review Manager 5.4 for data analysis. The current meta-analysis incorporated a total of 38 studies, comprising 50 sets of randomized controlled trials, to investigate the influence of different TGCFs and OITs on plyometric training. The Cochrane risk assessment tool indicated that all the included studies were classified as low risk. Various TGCFs in plyometric training positively affected CMJ and SJ heights in adolescents. The TGCF of less than 900 was ideal for enhancing CMJ, whereas more than 1400 was effective for SJ. The optimal OIT was 400-600 min, specifically, 500-600 min for CMJ and 400-500 min for SJ. Plyometric training improves jumping ability in adolescents. Lower ground contact frequency (< 900 contacts) enhances CMJ, while higher ground contact frequency (> 1400 contacts) is more effective for SJ. Optimal intervention time ranges from 400 to 600 min, with 500 to 600 min benefiting CMJ and 400 to 500 min improving SJ.

Mental health survey of medical personnel during pre-job training in a closed-loop management system during the COVID-19 pandemic.

Object: With the aim of enhancing prevention and regional control of epidemics, the mental health status of medical personnel was analyzed before the implementation of closed-loop management during the COVID-19 pandemic in the regional hospital representative. Methods: In accordance with directives from the unified deployment of the national and regional health bureaus, and following the inclusion and exclusion criteria, from September 2021 to November 2022, all medical personnel assigned to a closed-loop working environment by Guangzhou Panyu Central Hospital were enrolled as research subjects through cluster sampling method. Using a cross-sectional survey method, relevant data such as age, gender, professional title, and mental health status were collected. The Patient Health Questionnaire-9 (PHQ-9) scale, the Generalized Anxiety Disorder-7 (GAD-7) scale, and the Insomnia Severity Index (ISI) scale were administered. Logistic regression analysis was used to study the influencing factors of depression, anxiety, and insomnia. Single factor logistic regression analysis was performed first, followed by multiple factor logistic regression analysis. Results: A total of 500 valid responses were received. Depression was reported by a higher proportion of physicians than nurses. Anxiety was reported by higher proportion of men than women and by a higher proportion of physicians than nurses. Medical personnel under the age of 30 years reported fewer symptoms of insomnia than those over the age of 41 years, and medical personnel with intermediate professional titles reported more severe symptoms of insomnia than junior personnel. There was no significant difference between the results of the three questionnaires for medical personnel from other hospital departments or in the different type of closed-loop work environments. Conclusion: During the pandemic, conducting psychological health assessments for medical personnel undergoing pre-job training in closed-loop management was beneficial for the timely detection of psychological problems. Although this study only conducted a cluster sampling survey and lacked comparative analysis on other medical institutions, it still suggested that it was necessary to strengthen timely psychological counseling and intervention for senior male physicians.

Application of Konjac Glucomannan with Chitosan Coating in Yellow Alkaline Noodles.

To improve the quality of the characteristics of yellow alkaline noodles and enrich their nutritional value, konjac glucomannan (KGM) with or without chitosan coating were added to noodles, and their application effects were investigated in terms of color, texture, water absorption, starch digestion, total plate count (TPC) and microstructure. Chitosan-konjac glucomannan (CK) complex was firstly prepared by embedding konjac powder with chitosan sol. After embedding, the hydrophilicity of KGM decreased significantly. Then, either CK or native KGM were mixed evenly with flour before saline water, and soda was subsequently added to produce noodles. Compared with native KGM, CK provided the noodles with a higher brightness and a lighter yellow color. In terms of texture properties, although the firmness of CK noodles was weaker than that of KGM noodles, the tensile properties were enhanced. After embedding, the water absorption of CK noodles decreased and the content of resistant starch (RS) in the noodles increased. During storage, the TPC in CK noodles was significantly lower than that in KGM noodles. At a CK content of 5%, the noodles presented a lightness of 87.41, a b value of 17.75, a shear work of 39.9 g·cm, a tensile distance of 84.28 cm, a water absorption of 69.48%, a RS content of 17.97% and a TPC of 2.74 lg CFU/g at 10 days. In general, KGM with chitosan coating could improve the physicochemical qualities of noodles and extend their shelf life to a certain extent.

Sesamol serves as a p53 stabilizer to relieve rheumatoid arthritis progression and inhibits the growth of synovial organoids.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease known as a leading cause of disability with considerable mortality. Developing alternative drugs and targets for RA treatment is an urgent issue. Sesamol is a phenolic compound isolated from natural food sesame (Sesamum indicum L.) with various biological activities. PURPOSE: The current research intended to illuminate the bioactivity and mechanisms of sesamol in RA fibroblast-like synoviocytes (FLS), and aimed to estimate the potential clinical application value of sesamol in RA treatment. METHODS: CCK-8, EdU, and flow cytometry assays, as well as transwell tests were applied to observe the effects of sesamol on the abnormal functions of RA-FLS. Moreover, synovial organoids and a collagen-induced arthritis (CIA) mouse model were constructed to further explore the therapeutic capacity of sesamol on RA. Furthermore, RNA sequencing combined with quantitative real-time PCR assay, Western blot as well as co-immunoprecipitation were employed to clarify the mechanism of sesamol in regulating RA progression. RESULTS: Sesamol suppressed the proliferation through inhibiting DNA replication, triggering cell cycle arrest and apoptosis of RA-FLS. Besides, sesamol impaired RA-FLS migration and invasion. Interestingly, sesamol inhibited the growth of constructed synovial organoids and alleviated RA symptoms in CIA mice. Moreover, RNA sequencing further implicated p53 signaling as a downstream pathway of sesamol. Furthermore, sesamol was shown to decrease p53 ubiquitination and degradation, thereby activating p53 signaling. Finally, bioinformatics analyses also highlighted the importance of sesamol-regulated networks in the progression of RA. CONCLUSIONS: Our investigation demonstrated that sesamol served as a novel p53 stabilizer to attenuate the abnormal functions of RA-FLS via facilitating the activation of p53 signaling. Moreover, our study highlighted that sesamol might be an effective lead compound or candidate drug and p53 could be a promising target for the therapy of RA.

The welfare effects of impoverished rural areas: Review and research prospects.

The relationship between rural poverty and welfare effects is a significant social issue, as poor areas face challenges like fragile livelihoods, nutritional imbalances, and inadequate policy regulation. Studying welfare effects in impoverished rural areas is vital for addressing capability poverty and achieving the United Nations SDGs. This study examines three decades of research, using a quantitative literature analysis and traditional literature review. It identifies three research characteristics: focus on poverty and inequality, the impact of rural vulnerability on welfare effects, and farm households' higher psychological needs. Research encompasses four key areas: theoretical research, measurement of welfare effects, factors influencing welfare effects, and strategies for improvement. Future research should link welfare policies to enhance rural nutrition, clarify rural-community interactions, and improve subject relations to boost overall welfare.

Comprehensive Investigation of the Influence of High-Altitude Hypoxia on Clopidogrel Metabolism and Gut Microbiota.

BACKGROUND: The amount of metabolites converted into active metabolites is correspondingly reduced since only more than 50% of clopidogrel is absorbed. OBJECTIVE: Exploring the effect of gut microbiota altered by altitude hypoxia on the pre-absorption metabolism of clopidogrel. METHODS: In vitro and in vivo experiments were conducted to analyze the metabolism of clopidogrel through LCMS/ MS, while 16S rRNA analysis was used to investigate the changes in the gut microbiota of high-altitude animals. RESULTS: We demonstrated that the intestinal flora is involved in the metabolism of clopidogrel through in vivo and in vitro experiments. In addition, the plateau environment caused changes in the number and composition of intestinal microbes. Intriguingly, alterations in the microbial population could lead to an increase in the pre-absorption metabolism of clopidogrel after rapid entry into the plateau, the amount of absorbed blood is thus reduced, which may affect the bioavailability and therapeutic effect of clopidogrel. CONCLUSION: Our results not only as a first clinical reference for dose adjustment of clopidogrel in high-altitude environments but also would be helpful to provide a statement on the broader significance within the field of pharmacokinetics or personalized medicine.