Targeting BRIX1 via Engineered Exosomes Induces Nucleolar Stress to Suppress Cancer Progression.

Elevated ribosome biogenesis correlates with the rapid growth and progression of cancer. Targeted blockade of ribosome biogenesis induces nucleolar stress, which preferentially leads to the elimination of malignant cells. In this study, it is reported that the nucleolar protein BRIX1 is a critical regulator for the homeostasis between ribosome biogenesis and p53 activation. BRIX1 facilitated the processing of pre-rRNA by supporting the formation of the PeBoW complex. In addition, BRIX1 prevented p53 activation in response to nucleolar stress by impairing the interactions between MDM2 and the ribosomal proteins, RPL5, and RPL11, thereby triggering the resistance of cancer cells to chemotherapy. Conversely, depletion of BRIX1 induced nucleolar stress, which in turn activated p53 through RPL5 and RPL11, consequently inhibiting the growth of tumors. Moreover, engineered exosomes are developed, which are surface-decorated with iRGD, a tumor-homing peptide, and loaded with siRNAs specific to BRIX1, for the treatment of cancer. iRGD-Exo-siBRIX1 significantly suppressed the growth of colorectal cancer and enhanced the efficacy of 5-FU chemotherapy in vivo. Overall, the study uncovers that BRIX1 functions as an oncoprotein to promote rRNA synthesis and dampen p53 activity, and also implies that targeted inhibition of BRIX1 via engineered exosomes can be a potent approach for cancer therapy.

[Distribution of 21 organic ophospesters and their metabolites in drinking water in Dongcheng District of Beijing and their health hazard assessment in 2023].

OBJECTIVE: To investigate the pollution of organophosphate esters(OPEs) and their metabolites in drinking water in Dongcheng District of Beijing, and to assess the exposure risk of adults in drinking water. METHODS: The contents of 14 OPEs and 7 metabolites in drinking water were determined by automatic solid phase extraction, isotope dilution and liquid chromatography tandem mass spectrometry. The average daily potential dose(ADD) were calculated based on the recommended intake of drinking water. RESULTS: Seventeen pieces of tap water and 30 pieces of packaged drinking water collected by supermarket were measured. OPEs and di-OPEs were widely detected in drinking water(11 kinds of OPEs and 6 kinds of di-OPEs with the detection rate of more than 50%). The ΣOPEs range was 16.8 to 177ng/L, and the Σdi-OPEs range was 0.328 to 16.3 ng/L. The average daily dose of adult population was calculated: the ADD of 14 kinds of ΣOPEs in male and female were 3.15 and 3.10 ng/(kg·BW·d), and the P95 exposure was 6.95 and 7.00 ng/(kg·BW·d), respectively. The ADD of the seven Σdi-OPEs in male and female were 0.150 and 0.147 ng/(kg·BW·d), and the P95 exposure was 0.330 and 0.332 ng/(kg·BW·d), respectively. The hazard quotient(HQ) of exposure to OPEs through drinking water, calculated using the EPA's oral reference dose assessment, was much less than 1. CONCLUSION: The current exposure of OPEs via drinking water poses a low health risk to adult residents in Dongcheng District. However, due to the lack of Health-based guidance values for the metabolites of OPEs, the exposure risk may be underestimated.

Current situation and relationship between occupational stress, burn-out and sleep quality among ambulance drivers: a cross-sectional study.

OBJECTIVE: To understand the current status of occupational stress, occupational burn-out and sleep quality among ambulance drivers in Hengyang, China and to analyse the relationship between occupational stress, occupational burn-out and sleep quality of ambulance drivers. DESIGN: A cross-sectional study. SETTING: Prehospital emergency centre of third-class hospital in Hengyang, China. PARTICIPANTS: From October 2023 to December 2023, a cross-sectional survey was conducted, with 213 ambulance drivers from Hengyang, China, selected as participants. METHODS: General demographic questionnaires, the Chinese Occupational Stress Inventory, the Maslach Burnout Inventory and the Pittsburgh Sleep Quality Index were used for data collection and analysis. RESULTS: Occupational stress among ambulance drivers was positively correlated with occupational burn-out and sleep quality (r=0.528, 0.447, both p<0.01) while occupational burn-out was positively correlated with sleep quality (r=0.394, p<0.01). Occupational burn-out partially mediated the relationship between occupational stress and sleep quality among ambulance drivers, with a mediation effect value of 0.168, accounting for 26.09% of the total effect. CONCLUSION: The sleep quality of ambulance drivers in Hengyang, China is suboptimal, with occupational stress directly predicting sleep quality. Occupational burn-out plays a partial positive mediating role between occupational stress and sleep quality among ambulance drivers. Reducing occupational stress and burn-out is beneficial for improving the sleep quality of ambulance drivers.

Effect of light on ascorbic acid biosynthesis and bioinformatics analysis of related genes in Chinese chives.

Ascorbic acid (AsA) is an essential nutritional component and powerful antioxidant in vegetables, and in plants, AsA levels are regulated by light. AsA levels in the leaves of Chinese chive (Allium tuberosum Rottler ex Spr), a popular vegetable, are poorly understood. Thus, this study was performed to assess the influence of light on AsA biosynthesis in chive and select related genes (AtuGGP1 and AtuGME1); in addition, bioinformatic analyses and gene expression level assays were performed. The biological information obtained for AtuGGP1 and AtuGME1 was analysed with several tools, including NCBI, DNAMAN, and MEGA11. After different light treatments were performed, the Chive AsA content and AtuGGP1 and AtuGME1 expression levels were determined. These results suggest that 1) compared with natural light, continuous darkness inhibited AsA synthesis in chives. 2) The amino acid sequences of AtuGGP1 and AtuGME1 are very similar to those of other plants. 3) The trends observed for the expression levels of AtuGGP1 and AtuGME1 were consistent with the AsA content observed in chives. Hence, we speculated that light controls AsA biosynthesis in chives by regulating AtuGGP1 and AtuGME1 expression. This study provided impactful and informative evidence regarding the functions of GGP and GME in chives.

Corrigendum: Single-cell RNA sequencing of peripheral blood mononuclear cells from acute myocardial infarction.

[This corrects the article DOI: 10.3389/fimmu.2022.908815.].

The prerequisites and clinical outcomes of ipsilateral C7 nerve root transfer to the upper trunk for adult C5-C6 brachial plexus injuries.

PURPOSE: Although ipsilateral C7 nerve transfer is used for the treatment of C5-C6 brachial plexus injuries, accurately evaluating the functional quality of the donor nerve (ipsilateral C7 nerve root) is difficult, especially when the C7 nerve root is slightly injured. The purpose of this study was to determine the indicators to evaluate the quality of the ipsilateral C7 nerve and assess the clinical outcomes of this procedure. METHODS: This study employed the following three indicators to assess the quality of the ipsilateral C7 nerve: (1) the muscle strength and electrophysiological status of the latissimus dorsi, triceps brachii, and extensor digitorum communis; (2) the sensibility of the radial three digits, especially the index finger; and (3) the intraoperative appearance, feel and electrophysiological status of the ipsilateral C7 nerve root. Transfer of the ipsilateral C7 nerve root to the upper trunk was implemented only when the following three tests were conducted, the criteria were met, and the clinical outcomes were assessed in eight patients with C5-C6 brachial plexus injuries. RESULTS: Patients were followed-up for an average of 90 ± 42 months. At the final follow-up, all eight patients achieved recovery of elbow flexion, with five and three patients scoring M4 and M3, respectively, according to the Medical Research Council scoring. The shoulder abduction range of motor recovery averaged 86 ± 47° (range, 30°-170°), whereas the shoulder external rotation averaged 51 ± 26° (range, 15°-90°). CONCLUSION: Ipsilateral C7 nerve transfer is a reliable and effective option for the functional reconstruction of the shoulder and elbow after C5-C6 brachial plexus injuries when the three prerequisites are met.

The landscape of N1-methyladenosine (m1A) modification in mRNA of the decidua in severe preeclampsia.

Recent discoveries in mRNA modification have highlighted N1-methyladenosine (m1A), but its role in preeclampsia (PE) pathogenesis remains unclear. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify m1A peaks and the expression profile of mRNA in the decidua of humans with early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). We assessed the m1A modification patterns in preeclamptic decidua using 10 m1A modulators. Our bioinformatic analysis focused on differentially methylated mRNAs (DMGs) and differentially expressed mRNAs (DEGs) in pairwise comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE, as well as m1A-related DEGs. The comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE identified 3110, 2801, and 2818 DMGs, respectively. We discerned three different m1A modification patterns from this data. Further analysis revealed that key PE-related DMGs and m1A-related DEGs predominantly influence signaling pathways critical for decidualization, including cAMP, MAPK, PI3K-Akt, Notch, and TGF-ß pathways. Additionally, these modifications impact pathways related to vascular smooth muscle contraction, estrogen signaling, and relaxin signaling, contributing to vascular dysfunction. Our findings demonstrate that preeclamptic decidua exhibits unique mRNA m1A modification patterns and gene expression profiles that significantly alter signaling pathways essential for both decidualization and vascular dysfunction. These differences in m1A modification patterns provide valuable insights into the molecular mechanisms influencing the decidualization process and vascular function in the pathogenesis of PE. These m1A modification regulators could potentially serve as potent biomarkers or therapeutic targets for PE, warranting further investigation.

Electroacupuncture activates the peroxisome proliferators-activated receptor pathway to improve the phenotype of cerebral palsy.

AIM: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague-Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms. METHODS: Gait analysis and Y-maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype. RESULTS: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement. CONCLUSION: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP.

Growth inhibition of subcutaneous tumor with glioma cells in nude mice by silencing TLR4.

This study investigated the regulatory impact of Toll-like receptor 4 (TLR4) gene on glioma cell proliferation and apoptosis, elucidating the molecular mechanisms underlying TLR4-induced growth inhibition in vivo. U-87MG-Sh and U-87MG-NC cells, with silenced TLR4 and negative control plasmid respectively, were established. Eighteen nude mice, divided into transfection, negative control, and blank control groups, were inoculated with corresponding cells. Over four weeks, the transfection group exhibited significantly reduced tumor growth rates, smaller mass and volume, and lower growth activity compared to controls. Histological analysis revealed sparse tumor cells, increased fibrous connective tissue, and slower angiogenesis in the transfection group. Flow cytometry demonstrated a lower proliferation index and increased G0/1 cell count in the transfection group. mRNA levels of TLR4, NF-κB, and CyclinD1 were significantly lower in the transfection group. TLR4 silencing correlated with U-87MG cell proliferation regulation, growth inhibition, NF-κB and CyclinD1 modulation, and induction of cell cycle arrest and apoptosis. These findings suggest TLR4 as a potential gene therapy target for glioma.

Susceptibility to e-cigarette adoption among tobacco-naïve youths: a cross-sectional study in Shenzhen, China.

Background: The rise in e-cigarette use among youth is a significant global public health issue. It is important to identify those at increased risk and implement effective strategies to reduce e-cigarette popularity among the youth. Objective: This study aims to identify predictors of e-cigarette uptake in youths with no prior tobacco use, considering individual, familial and the broader societal environmental factors. Methods: For this investigation, a group of 2,487 tobacco-free youths was selected from 15 high schools in Shenzhen, China. Susceptibility to e-cigarettes was determined by assessing the possibility of future use and the openness to trying e-cigarettes if presented by friends. Both chi-square tests and logistic regression were applied to identify factors linked to susceptibility to e-cigarette use. Results: Among the respondents, 5.5% (n = 136) were found to be susceptible to e-cigarette use. The analysis revealed factors tied to this risk: perceptions of e-cigarettes, the impact of vaping peers, paternal parenting styles, the extent of social support, exposure to messages both for and against e-cigarettes use, and secondhand smoke (SHS) exposure. Youths who downplayed the addictive nature of e-cigarettes (aOR = 2.01; 95% CI: 1.14-3.55; p = 0.016), those with friends who engaged in vaping (aOR = 3.43-7.64; 95%CI: 2.36-20.42; p < 0.001), those experiencing over-protective or rejective maternal parenting (aOR = 1.68-3.01; 95%CI: 1.11-5.77; p = 0.001-0.014) or rejective paternal parenting (aOR = 3.63; 95%CI: 1.99-6.59; p < 0.001), those aware of e-cigarette advertisements (aOR = 1.82; 95%CI: 1.28-2.60; p = 0.001), and those exposed to SHS at home (aOR = 1.68; 95%CI: 1.17-2.41; p = 0.005) or at public places (aOR = 1.72-1.79; 95%CI: 1.21-2.57; p = 0.002-0.003) were more prone to e-cigarettes. In contrast, youths who believed using e-cigarettes reduces one's attractiveness (aOR = 0.34; 95%CI: 0.16-0.72; p = 0.005) or perceived that vaping made social interactions less enjoyable (aOR = 0.26; 95%CI: 0.12-0.58; p = 0.001), those who benefited from high social support (aOR = 0.30-0.60; 95%CI: 0.17-0.97; p < 0.001), and those who noticed message about e-cigarettes' adverse consequence (aOR = 0.54; 95%CI: 0.38-0.77; p = 0.001) were less likely to be inclined toward e-cigarette use. Conclusion: The propensity of the youth to e-cigarette usage is shaped by a multiple element. An all-encompassing strategy that addresses the individual, familial, and the broader societal aspects is imperative for the effective prevention of e-cigarette initiation among youth.

Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.

Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.

KLF4 inhibited the senescence-associated secretory phenotype in ox-LDL-treated endothelial cells via PDGFRA/NAMPT/mitochondrial ROS.

BACKGROUND: Inflammation is one of the significant consequences of ox-LDL-induced endothelial cell (EC) dysfunction. The senescence-associated secretory phenotype (SASP) is a critical source of inflammation factors. However, the molecular mechanism by which the SASP is regulated in ECs under ox-LDL conditions remains unknown. RESULTS: The level of SASP was increased in ox-LDL-treated ECs, which could be augmented by KLF4 knockdown whereas restored by KLF4 knock-in. Furthermore, we found that KLF4 directly promoted PDGFRA transcription and confirmed the central role of the NAPMT/mitochondrial ROS pathway in KLF4/PDGFRA-mediated inhibition of SASP. Animal experiments showed a higher SASP HFD-fed mice, compared with normal feed (ND)-fed mice, and the endothelium of EC-specific KLF4-/- mice exhibited a higher proportion of SA-ß-gal-positive cells and lower PDGFRA/NAMPT expression. CONCLUSIONS: Our results revealed that KLF4 inhibits the SASP of endothelial cells under ox-LDL conditions through the PDGFRA/NAMPT/mitochondrial ROS. METHODS: Ox-LDL-treated ECs and HFD-fed mice were used as endothelial senescence models in vitro and in vivo. SA-ß-gal stain, detection of SAHF and the expression of inflammatory factors determined SASP and senescence of ECs. The direct interaction of KLF4 and PDGFRA promotor was analyzed by EMSA and fluorescent dual luciferase reporting analysis.

Design, synthesis, and biological evaluation of novel chrysin derivatives as poly(ADP-ribose) polymerase 1 (PARP1) inhibitors for the treatment of breast cancer.

In this study, we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly (ADP-ribose) polymerase 1 (PARP1). Among these derivatives, compound 5d emerged as the most effective chrysin-based inhibitor of PARP1, with an IC50 value of 108 nmol·L-1. This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage. Furthermore, 5d induced apoptosis and caused an extended G1/S-phase in these cell lines. Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1. In vivo, in a xenograft model, 5d effectively reduced tumor growth by downregulating PARP1 expression. Overall, compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

[Determination of 21 organophosphate esters and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a method for simultaneous determination of 21 organophosphate esters(OPEs) and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry. METHODS: The drinking water was purified by automatic solid phase extraction with HLB column, eluted by methanol, determined by liquid chromatography tandem mass spectrometry with ACQUITY UPLC BEH(100 mm×2.1mm, 1.7 µm) column, and quantified by internal standard method. RESULTS: The optimized method could simultaneously detect 21 organophosphate esters and their metabolites in drinking water. The detection limit was 0.01-0.24 ng/L, the quantitation limit was 0.03-0.77 ng/L. The recovery range was 57.6%-121.2% and the relative standard deviation is 1.2%-11.1% when the concentration was 0.8-20 ng/L. Senventeen tap water and 30 packaged drinking water collected by the supermarket were measured. The ΣOPEs range was 16.8-177 ng/L, and the Σdi-OPEs range was 0.328-16.3ng/L, indicating the exposure risk of organophosphates and their metabolites in water. CONCLUSION: The pretreatment of the method is simple, automatic and sensitive, and is suitable for simultaneous high-throughput determination of organophosphate esters and their metabolites in large quantities of drinking water.

Causal Relationship between Parkinson's Disease with Heart and Vascular Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: The aim of this study was to investigate the causal relationship between Parkinson's disease (PD) and myocardial infarction (MI), atrial fibrillation and flutter (AF), and venous thromboembolism (VTE) by Mendelian randomization (MR) analysis. METHODS: By using data from publicly available genome-wide association studies from databases, single nucleotide polymorphisms were screened as instrumental variables, and the MR analysis was finished by inverse-variance weighted (IVW), MR-egger, weighted median methods. RESULTS: The primary IVW method showed a negative association between genetically predicted PD and risk of MI (OR = 0.9989; 95% CI: 0.9980-0.9998; p = 0.02). However, PD was not significantly associated with AF or VTE. CONCLUSION: This study suggests a negative association between PD with MI, which implies that PD has a protective effect on MI.

Effects of pressure-controlled ventilation targeting end-inspiratory flow rate on pulmonary complications and inflammation levels in patients undergoing spinal surgery in the prone position: a randomized clinical trial.

BACKGROUND: This study assessed the impact of pressure-controlled ventilation (PCV) focusing on end-inspiratory flow rate on the incidence of postoperative pulmonary complications (PPCs) and inflammation levels in patients undergoing spinal surgery in the prone position. METHODS: A total of 187 patients who underwent posterior spinal surgery were enrolled and randomly divided into 3 groups: 61 in the volume-controlled ventilation (VCV) group (group V), 62 in the PCV-volume-guaranteed (VG) group (group P1), and 64 in the PCV-VG end-expiratory zero flow rate group (group P2). Indicators including tidal volume (VT), peak airway pressure (Ppeak), and dynamic lung compliance (Cdyn) were recorded. The Ppeak, Cdyn, PETCO2, and oxygenation index (PaO2/FiO2) after intubation (T0), after prone position (T1), 60 min after prone position (T2), and after supine position at the end of surgery (T3) of the three groups were collected. RESULTS: In the within-group comparison, compared with T0, Ppeak increased at T1 - 2 in groups V and P1 (P < 0.01), whereas it decreased at T1 - 3 in group P2 (P < 0.01). Cdyn decreased at T1 - 2 and PaO2/FiO2 increased at T1 - 3 in all three groups (P < 0.01), and PaO2/FiO2 increased at T1 - 3 (P < 0.01). Compared with group V, Ppeak decreased at T0 - 3 in group P1 (P < 0.01) and at T1 - 3 in group P2 (P < 0.01), while Cdyn increased at T0 - 3 in groups P1 and P2 (P < 0.01). Compared with group P1, Ppeak was elevated at T0 (P < 0.01) and decreased at T1 - 3 (P < 0.05), and Cdyn was elevated at T0 - 3 in group P2 (P < 0.01). The total incidence of PPCs in group P2 was lower than that in group V (P < 0.01). Compared with the preoperative period, serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels were increased at 24 and 72 h after surgery in group V (P < 0.01), whereas that was increased at 24 h after surgery in group P1 and group P2 (P < 0.01). Compared with group V, serum IL-6 and CRP levels were reduced at 24 h after surgery in groups P1 and P2 (P < 0.01 or < 0.05). CONCLUSION: In patients undergoing spinal surgery in the prone position, PCV-VG targeting an end-inspiratory zero flow rate lowers the incidence of PPCs and inflammation levels.

The role of education attainment on 24-hour movement behavior in emerging adults: evidence from a population-based study.

Purpose: The purpose of this study was to explore the relationship between education level and health behavior including sleep, work activity, exercise activity, and sedentary behavior among emerging adults. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2018. The study sample included 4,484 emerging adults aged 18-25 years and the weighted participants were 30,057,813. Weighted multivariable regression analysis was performed to investigate the association between education level and the aforementioned health behavior, adjusting for age, gender, race/ethnicity, marital status, poverty-income ratio, BMI, smoking, and alcohol drinking status. Results: This study revealed that higher education level was associated with shorter sleep duration [Fully adjusted model, ß (95% CI): -0.588 (-0.929, -0.246), p < 0.001]. Additionally, those with higher education levels were more likely to allocate time in sedentary behavior [ß (95% CI): 90.162 (41.087, 139.238), p < 0.001]. Moreover, higher education level was related to less work activity [ß (95% CI): -806.991 (-1,500.280, -113.703), p = 0.023] and more exercise activity time [ß (95% CI): 118.196 (-21.992, 258.385), p = 0.097]. Subgroup analysis further verified this trend and detected that males with higher education level tended to participate in less work activity [ß (95% CI): -1,139.972 (-2,136.707, -143.237), p = 0.026] while females with higher education level tended to engage in more exercise activity [Fully adjusted model, ß (95% CI): 141.709 (45.468, 237.950), p = 0.004]. Conclusion: This study highlighted the importance of education level as a significant factor in promoting healthy behavior among emerging adults. The findings underscored the need for the Ministry of Education to prioritize educating this demographic about the significance of maintaining adequate sleep patterns and reducing sedentary habits. Encouraging them to allocate more time for work and physical activities can significantly contribute to their overall wellbeing and success, ultimately fostering a healthier next generation.

Apigenin analogs as α-glucosidase inhibitors with antidiabetic activity.

This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a Ki value of 2.61 µM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health.

Progress in the clinical treatment of keloids.

Keloid is a pathological scar that is higher than the skin surface following skin damage. Its lesion range often extends beyond the original damage boundary and does not naturally subside over time. Its pathogenesis is very complex, currently the main causes include fibroblast excessive proliferation, collagen and extracellular matrix (Extracellular matrix, ECM) excessive deposition, excessive angiogenesis, and so on. The traditional treatment method primarily involves surgical intervention, but it is associated with a high recurrence rate post-surgery. Consequently, many treatment methods are derived according to the different clinical characteristics of keloid. This paper will review the therapeutic progress in recent years from surgical treatment, physiotherapy, drug therapy, and biological therapy, with the goal of offering valuable insights for the clinical treatment of keloids.