CKIP-1 silencing suppresses OSCC via mitochondrial homeostasis-associated TFAM/cGAS-STING signalling axis.

Limited effective targets have challenged the treatment of oral squamous cell carcinoma (OSCC). Casein kinase 2 interacting protein 1 (CKIP-1) is a scaffold protein involved in various diseases. However, the role of CKIP-1 in OSCC remains unclear. The aim of this study was to explore the regulatory role of CKIP-1 in OSCC, as well as the involved mechanism. First, higher expression of CKIP-1 in OSCC tissues and cell lines were found. Series of gain- and loss-of-function experiments demonstrated suppressed malignant behaviours and enhanced apoptosis of OSCC cells when CKIP-1 was silenced. Also, inhibited tumour growth in CKIP-1-silenced group were proved. Further, mitochondrial transcription factor A (TFAM) downregulation, increased ROS production, decreased mitochondrial membrane potential and cGAS-STING activation in CKIP-1-silenced group were observed. The involvement of mitochondrial homeostasis-related TFAM/cGAS-STING axis in CKIP-1-silenced OSCC cells was finally demonstrated by tetramethylpyrazine (TMP) that inhibits TFAM degradation. Taken together, our study demonstrated that CKIP-1 silencing could significantly antagonize OSCC via TFAM/cGAS-STING axis, which may provide a candidate target for OSCC treatment.

Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair.

Macrophages may acquire a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements underpinning this process are incompletely understood. Here, we show that posttranslational modification (PTM) of PPARγ regulates lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrates function of reparative macrophages. In injured tissues, repair signaling leads to decreased macrophage PPARγ threonine 166 (T166) phosphorylation, which results in a partially active PPARγ transcriptional program comprised of increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby increased lipogenesis. The accumulated lipids serve as signaling molecules, triggering STAT3-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for protein secretion. Genetic or pharmacological inhibition of PPARγ T166 phosphorylation promotes the reparative function of macrophages and facilitates tissue regeneration. In summary, our work identifies PPARγ T166-regulated lipid biosynthesis as an essential pathway for meeting the anabolic demands of the activation and function of macrophages and provides a rationale for potential therapeutic targeting of tissue repair.

In Situ Characterization Techniques for Electrochemical Nitrogen Reduction Reaction.

The electrochemical reduction of nitrogen to produce ammonia is pivotal in modern society due to its environmental friendliness and the substantial influence that ammonia has on food, chemicals, and energy. However, the current electrochemical nitrogen reduction reaction (NRR) mechanism is still imperfect, which seriously impedes the development of NRR. In situ characterization techniques offer insight into the alterations taking place at the electrode/electrolyte interface throughout the NRR process, thereby helping us to explore the NRR mechanism in-depth and ultimately promote the development of efficient catalytic systems for NRR. Herein, we introduce the popular theories and mechanisms of the electrochemical NRR and provide an extensive overview on the application of various in situ characterization approaches for on-site detection of reaction intermediates and catalyst transformations during electrocatalytic NRR processes, including different optical techniques, X-ray-based techniques, electron microscopy, and scanning probe microscopy. Finally, some major challenges and future directions of these in situ techniques are proposed.

Fisetin Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglia/Macrophage M1 Polarization and JAK2/STAT3 Signaling Pathway.

Spinal cord injury (SCI) is one of the most serious health problems, with no effective therapy. Recent studies indicate that Fisetin, a natural polyphenolic flavonoid, exhibits multiple functions, such as life-prolonging, antioxidant, antitumor, and neuroprotection. However, the restorative effects of Fisetin on SCI and the underlying mechanism are still unclear. In the present study, we found that Fisetin reduced LPS-induced apoptosis and oxidative damage in PC12 cells and reversed LPS-induced M1 polarization in BV2 cells. Additionally, Fisetin safely and effectively promoted the motor function recovery of SCI mice by attenuating neurological damage and promoting neurogenesis at the lesion. Moreover, Fisetin administration inhibited glial scar formation, modulated microglia/macrophage polarization, and reduced neuroinflammation. Network pharmacology, RNA-seq, and molecular biology revealed that Fisetin inhibited the activation of the JAK2/STAT3 signaling pathway. Notably, Colivelin TFA, an activator of JAK2/STAT3 signaling, attenuated Fis-mediated neuroinflammation inhibition and therapeutic effects on SCI mice. Collectively, Fisetin promotes functional recovery after SCI by inhibiting microglia/macrophage M1 polarization and the JAK2/STAT3 signaling pathway. Thus, Fisetin may be a promising therapeutic drug for the treatment of SCI.

Origin of a Topotactic Reduction Effect for Superconductivity in Infinite-Layer Nickelates.

Topotactic reduction utilizing metal hydrides as reagents has emerged as an effective approach to achieve exceptionally low oxidization states of metal ions and unconventional coordination networks. This method opens avenues to the development of entirely new functional materials, with one notable example being the infinite-layer nickelate superconductors. However, the reduction effect on the atomic reconstruction and electronic structures-crucial for superconductivity-remains largely unresolved. We designed two sets of control Nd_{0.8}Sr_{0.2}NiO_{2} thin films and used secondary ion mass spectroscopy to highlight the absence of reduction-induced hydrogen intercalation. X-ray absorption spectroscopy revealed a significant linear dichroism with dominant Ni 3d_{x2-y2} orbitals on superconducting samples, indicating a Ni single-band nature of infinite-layer nickelates. Consistent with the superconducting T_{c}, the Ni 3d orbitals asymmetry manifests a domelike dependence on the reduction duration. Our results unveil the critical role of reduction in modulating the Ni-3d orbital polarization and its impact on the superconducting properties.

Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality in critical patients with diabetic ketoacidosis: a retrospective analysis of the eICU database.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis. Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death. Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023). Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency.

[Occurrence and environmental risks of antibiotics in surface water of China].

Antibiotics as emerging pollutants are frequently detected in surface water, raising concerns about the associated risk of antibiotic resistance genes (ARGs). Despite the widespread apprehension, there are still research gaps in the occurrence of antibiotic pollution in surface water and the associated ecological risks to aquatic organisms in China. Here, we established a dataset of antibiotic pollution in surface water in China during 2018-2022, which encompassed 3 368 concentration values of 128 antibiotics reported in 124 articles. Our analysis showed that antibiotic concentrations were predominantly in the ng/L-µg/L range, reaching up to 26 µg/L. Notably, sulfonamides (e.g., sulfamethoxazole) and quinolones (e.g., ciprofloxacin) were frequently reported at high concentrations. The pollution degree of antibiotics represented by sulfamethoxazole, ciprofloxacin, roxithromycin, and tetracycline exhibited no significant variation across different years but was lower in summer than that in spring and autumn. Additionally, distinct spatial distribution characteristics of the pollution were observed. According to calculation results of the aquatic ecological risk assessment model and the weighted frequency, we proposed a list of priority antibiotics including clarithromycin, erythromycin, sulfamethoxazole, ofloxacin, and oxytetracycline in surface water. Last but not least, this study points out the deficiencies in current research on the occurrence and ecological risks of antibiotics in surface water of China and provides viable screening strategies and monitoring recommendations in this context.

3D Printing Elastocaloric TiNiCu Thermoelectric Shape Memory Alloys.

The development of new thermoelectric conversion and cooling materials is an important means of addressing global climate and heat emissions in the future. While heavy and toxic elements like tellurium and lead are traditionally used to make thermoelectric materials with poor mechanical properties, recent decades have seen a gradual push towards greener and more sustainable alternatives. One such potential alternative material for thermoelectric and thermal management applications would be the Nitinol (TiNi) shape memory alloy, due to their superior mechanical properties. In this study, we have investigated the use of 3D melt printing techniques that can be used to achieve thermoelectric performance and efficiency of elastic memory alloys below 500 °C.　The electrical and thermal properties of TiNiCu materials and their relation to morphology were investigated. All the alloys show similar effect sizes, their fatigue behavior is however different. By adjusting the composition of Ti and Ni elements and we have obtained memory alloys with high thermoelectric properties, with a 50% increase in power factor and a 100% increase in ZT values.

Effect of RNAi mediated silencing of DIB, JHE, and CAM on the diapause termination of Calliptamus italicus (Orthoptera: Acrididae) eggs.

BACKGROUND: Calliptamus italicus L. is a major pest in Xinjiang grassland. The diapause overwintering strategy is one of the important reasons for the large population of this pest. This study investigated the function of the genes associated with the release of diapause (DIB, JHE and CAM) in Calliptamus italicus by RNA interference (RNAi) technology to aid in its biological control. RESULTS: The expression levels of DIB and its downstream-associated genes (EcR and FTZ-F1) in the eggs injected with dsDIB for 12 h decreased by 96.6%, 55.8% and 81.8%, respectively. Diapause began to terminate on day 3, and development was almost complete on day 6. However, the head was significantly smaller. The expression levels of JHE and its downstream-associated genes (JHEH and VgR) at 48 h after dsJHE treatment decreased by 76.5%, 85.6% and 85.9%, respectively. The termination of diapause occured on day 3 of incubation. The development was basically complete on day 6, but the yolk had been incompletely absorbed. The expression of CAM and its downstream-associated genes (CAMK4 and MYL) at 24 h after dsCAM treatment decreased by 42.4%, 95.3% and 82.7%, respectively. Diapause termination was completed on day 4 for incubation, and development was abnormal on day 6. The absorption of yolk was incomplete. CONCLUSION: DIB, JHE and CAM can delay the diapause termination of Calliptamus italicus eggs to different degrees and can be developed as potential target genes for its biological control. © 2024 Society of Chemical Industry.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.

OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ±â€¯328.1 ng/mL, in contrast to the CC phenotype at 334.0 ±â€¯161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Esketamine Combined with Dexmedetomidine to reduce Visceral Pain During elective Cesarean Section Under Combined Spinal-Epidural Anesthesia: A double-Blind Randomized Controlled Study.

Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.

Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.

Development and validation of a predictive model for severe white matter hyperintensity with obesity.

Purpose: The purpose of the present study was to identify predictors of severe white matter hyperintensity (WMH) with obesity (SWO), and to build a prediction model for screening obese people with severe WMH without Nuclear Magnetic Resonance Imaging (MRI) examination. Patients subjects and methods: From September 2020 to October 2021, 650 patients with WMH were recruited consecutively. The subjects were divided into two groups, SWO group and non-SWO group. Univariate and Logistic regression analysis were was applied to explore the potential predictors of SWO. The Youden index method was adopted to determine the best cut-off value in the establishment of the prediction model of SWO. Each parameter had two options, low and high. The score table of the prediction model and nomogram based on the logistic regression were constructed. Of the 650 subjects, 487 subjects (75%) were randomly assigned to the training group and 163 subjects (25%) to the validation group. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. Results: Logistic regression demonstrated that hypertension, uric acid (UA), complement 3 (C3) and Interleukin 8 (IL-8) were independent risk factors for SWO. Hypertension, UA, C3, IL-8, folic acid (FA), fasting C-peptide (FCP) and eosinophil could be used to predict the occurrence of SWO in the prediction models, with a good diagnostic performance, Areas Under Curves (AUC) of Total score was 0.823 (95% CI: 0.760-0.885, p < 0.001), sensitivity of 60.0%, specificity of 91.4%. In the development group, the nomogram's AUC (C statistic) was 0.829 (95% CI: 0.760-0.899), while in the validation group, it was 0.835 (95% CI: 0.696, 0.975). In both the development and validation groups, the calibration curves following 1,000 bootstraps showed a satisfactory fit between the observed and predicted probabilities. DCA showed that the nomogram had great clinical utility. Conclusion: Hypertension, UA, C3, IL-8, FA, FCP and eosinophil models had the potential to predict the incidence of SWO. When the total score of the model exceeded 9 points, the risk of SWO would increase significantly, and the nomogram enabled visualization of the patient's WMH risk. The application prospect of our models mainly lied in the convenient screening of SWO without MRI examination in order to detect SWO and control the WMH hazards early.

Mechanochemical Formation of Poly(melamine-formaldehyde) Microplastic Fibers During Abrasion of Cleaning Sponges.

The abrasion of synthetic textile fibers is a significant factor in the generation of environmental microplastic fibers (MPFs). The extent to which polymer sponges designed specifically for surface cleaning have a tendency to release MPFs during normal use remains unknown. Here, the tribological behaviors of melamine cleaning sponges (also known as "magic erasers") with different strut densities against metal surfaces of different roughness were investigated using a reciprocating abrader. The MPFs formed by sponge wear under various conditions were characterized in terms of their morphology, composition, and quantity. They were mainly composed of poly(melamine-formaldehyde) polymer with linear or branched fiber morphologies (10-405 µm in length), which were formed through deformation and fracture of the struts within open cells of the sponges, facilitated by friction-induced polymer decomposition. The rate and capability of MPF production generally increased with increasing roughness of the metal surface and density of the struts, respectively. The sponge wear could release 6.5 million MPFs/g, which could suggest a global overall emission of 4.9 trillion MPFs due to sponge consumption. Our study reveals a hitherto unrecognized source of the environmental MPF contamination and highlights the need to evaluate exposure risks associated with these new forms of MPFs.

Correlation of serum matrix metalloproteinase 3 with osteoporosis in patients of postmenopausal rheumatoid arthritis.

Osteoporosis (OP) is a common complication of postmenopausal women with rheumatoid arthritis (RA). Herein, the objective of our study was to explore the correlation between serum matrix metalloproteinase 3 (MMP3) and OP among postmenopausal women with RA to foster better diagnosis and treatment. A total of 208 elderly postmenopausal women with RA were included in this study, with 83 patients diagnosed with OP after RA diagnosis and 125 patients without OP. Serum MMP3 levels and bone mineral density (BMD) were measured and compared. The predictive value of serum MMP3 for OP in this population was also analyzed using receiver operating curve (ROC) analysis. Postmenopausal women with RA and OP diagnosis had markedly higher serum MMP3 levels, compared to those without OP. ROC analysis showed that serum MMP3 had predictive value for OP. Additionally, a negative correlation was observed between serum MMP3 levels and BMD. High serum MMP3 levels were also found to be associated with high abnormal bone metabolism. We found that serum MMP3 levels are strongly correlated with OP in postmenopausal women with RA and that elevated levels of serum MMP3 are linked to low BMD and high abnormal bone metabolism. Serum MMP3 may be a useful biomarker for predicting OP in this population, and could potentially aid in the development of targeted prevention and treatment strategies.

[Prediction of quality markers of Angong Niuhuang Pills based on LC-MS and pull-down with SPR chips].

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 µmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

Lensless shadow microscopy-based shortcut analysis strategy for fast quantification of microplastic fibers released to water.

Fast quantification is the primary challenge in monitoring microplastic fiber (MPF) pollution in water. The process of quantifying the number of MPFs in water typically involves filtration, imaging on a filter membrane, and manual counting. However, this routine workflow has limitations in terms of speed and accuracy. Here, we present an alternative analysis strategy based on our high-resolution lensless shadow microscope (LSM) for rapid imaging of MPFs on a chip and modified deep learning algorithms for automatic counting. Our LSM system was equipped with wide field-of-view submicron-pixel imaging sensors (>1 cm2; ∼500 nm/pixel) and could simultaneously capture the projection image of >3-µm microplastic spheres within 90 s. The algorithms enabled accurate classification and detection of the number and length of >10-µm linear and branched MPFs derived from melamine cleaning sponges in each image (∼0.4 gigapixels) within 60 s. Importantly, neither MPF morphology (dispersed or aggregated) nor environmental matrix had a notable impact on the automatic recognition of the MPFs by the algorithms. This new strategy had a detection limit of 10 particles/mL and significantly reduced the time of MPF imaging and counting from several hours with membrane-based methods to just a few minutes per sample. The strategy could be employed to monitor water pollution caused by microplastics if an efficient sample separation and a comprehensive sample image database were available.

Association Between Preeclampsia and Blood Pressure in Offspring: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Pregnancy-induced preeclampsia is a severe pregnancy complication and preeclampsia has been associated with an increased risk of chronic hypertension for offspring. However, the magnitude of the overall effect of exposure to preeclampsia in pregnancy on blood pressure (BP) in offspring is unknown. This systematic review and meta-analysis was sought to systematically assess the effects of preeclampsia on the BP of the offspring. RECENT FINDINGS: Of 2550 publications identified, 23 studies were included. The meta-analysis indicated that preeclampsia increases the potential risk of hypertension in offspring. Systolic blood pressure (SBP) was 2.0 mm Hg (95% CI: 1.2, 2.8) and diastolic blood pressure (DBP) was 1.4 mm Hg (95% CI: 0.9, 1.9) higher in offspring exposed to pre-eclampsia in utero, compared to those born to normotensive mothers. The correlations were similar in stratified analyses of children and adolescents by sex, geographic area, ages, and gestational age. During childhood and young adulthood, the offspring of pregnant women with preeclampsia are at an increased risk of high BP. It is crucial to monitor their BP.

Extraction, purification, structural characterization, and biological activity of polysaccharides from Schisandra chinensis: A review.

Schisandra chinensis (SC), a plant of the Magnoliaceae family, commonly known as "North Schisandra chinensis", has been listed as a top-grade Chinese medicine in the Shennong Materia Medica Classic for its high medicinal value since ancient times. Polysaccharides from S. chinensis fruits (SCPs) are an active component in SC, which have various biological activity, including immune regulation, anti-tumor, antioxidant, liver protective, anti-inflammatory and hypoglycemic activity. Research has shown that the extraction methods of SCPs include hot water extraction, water extraction and alcohol precipitation, ultrasonic-assisted, microwave-assisted and so on. Different extraction methods can affect the yield and purity of polysaccharides, and to improve the extraction yield of SCPs, two or more extraction methods can be combined. SCPs are mainly composed of glucose, mannose, rhamnose, galactose, galacturonic acid and arabinose. This article aims to provide a systematic review of the research progress in the extraction and separation methods, structural characterization, and biological activity of SCPs both domestically and internationally in recent years. This deeply explores the pharmacological activity and action mechanism of SCPs, and provides a certain point of reference for the research and clinical application of SC.

Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r  = 0.17; P  < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ±â€…297.1 vs. 633.8 ±â€…305.5 µg/ml; P  = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ±â€…1.7 vs. 3.8 ±â€…2.0; P  = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ±â€…293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ±â€…165.6 ng/ml and 260.0 ±â€…36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ±â€…285.6 vs. 433.0 ±â€…227.2 ng/ml; P  = 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

Maize (Zea mays L.) Plants Alter the Fate and Accumulate Nonextractable Residues of Sulfamethoxazole in Farmland Soil.

The fate of sulfonamide antibiotics in farmlands is crucial for food and ecological safety, yet it remains unclear. We used [phenyl-U-14C]-labeled sulfamethoxazole (14C-SMX) to quantitatively investigate the fate of SMX in a soil-maize system for 60 days, based on a six-pool fate model. Formation of nonextractable residues (NERs) was the predominant fate for SMX in unplanted soil, accompanied by minor mineralization. Notably, maize plants significantly increased SMX dissipation (kinetic constant kd = 0.30 day-1 vs 0.17 day-1), while substantially reducing the NER formation (92% vs 58% of initially applied SMX) and accumulating SMX (40%, mostly bound to roots). Significant NERs (maximal 29-42%) were formed via physicochemical entrapment (determined using silylation), which could partially be released and taken up by maize plants. The NERs consisted of a considerable amount of SMX formed via entrapment (1-8%) and alkali-hydrolyzable covalent bonds (2-12%, possibly amide linkage). Six and 10 transformation products were quantified in soil extracts and NERs, respectively, including products of hydroxyl substitution, deamination, and N-acylation, among which N-lactylated SMX was found for the first time. Our findings reveal the composition and instability of SMX-derived NERs in the soil-plant system and underscore the need to study the long-term impacts of reversible NERs.