[Ecological characteristics and seasonal changes of macrozoobenthos in the waters of Miaodao Archipelago, China]. / åº™å²›ç¾¤å²›æµ·åŸŸå¤§åž‹åº•æ –åŠ¨ç‰©ç”Ÿæ€ç‰¹å¾åŠå­£èŠ‚å˜åŒ–.

To understand the macrozoobenthic community composition and spatial-temporal distribution characteristics of macrobenthos in the waters of Miaodao Archipelago, Yantai, Shandong and its response to habitat changes, we conducted surveys of macrobenthos and environmental elements in the waters of Miaodao Islands in May (spring), August (summer), and October (autumn) in 2022. Results showed that a total of 127 macrozoobenthic species were recorded, with Mollusca and Annelida (Polychaeta) as the dominant taxa, consisting of 47 and 45 species, respectively. The key dominant species included Sternaspis chinensis, Glycinde bonhourei, Moerella hilaris, and Amphioplus (Lymanella) japonicus. The average annual density and biomass of macrozoobenthos were 190 ind·m-2 and 28.69 g·m-2, respectively. There was no significant seasonal differences in density and biomass. The Shannon diversity index (H), evenness index (J), and richness index (D) averaged 3.10, 0.90, and 2.40, respectively. Cluster analysis results showed low similarity coefficients of community among the three seasons, suggesting a distinct distribution pattern. Factors such as bottom seawater temperature, chlorophyll a, nutrient, sediment grain size, and organic matter content could significantly influence the structure and diversity of macrozoobenthic community. Compared with historical research data, the Changdao National Wetland Nature Reserve and the implementation of enclosure aquaculture have led to notable changes in the dominant species of macrobenthos. Specifically, there was a noticeable decline in both density and H, and an increase in biomass and J. Additionally, body size of benthic fauna was transitioning from small to big.

Stop Ischemic Event to the Brain: Screening Risk Factors of Cerebrovascular Stenosis in Coronary Artery Disease Patients.

OBJECTIVES: In this study, we investigated the difference in risk factors between the 2 diseases, aiming to further clarify who needs to do ischemic cerebrovascular disease (ICVD)-related screening among coronary artery disease (CAD) patients. METHODS: Clinical data of 326 patients with first-episode CAD from June 1, 2017, to July 31, 2020, in the Chinese PLA General Hospital were retrospectively reviewed. Outcomes, including clinical features and laboratory examination, were taken. Features related to ICVD including the extension of intracranial arterial (internal carotid artery intracranial segment, middle cerebral artery M1 segment, anterior cerebral A1 segment, vertebrobasilar artery intracranial segment, posterior cerebral artery P1 segment) and carotid arterial (internal carotid artery extracranial segment, common carotid artery, subclavian artery) stenosis were detected. Risk factors for the occurrence of ICVD in patients with CAD were analyzed. RESULTS: Among patients with the onset of CAD, in comparison of the nonstenosis and stenosis of intracranial artery subgroups, there were statistical differences in the onset age, hypertension, and duration of hypertension as well as the biochemical indicators, including high-density lipoprotein and glycosylated hemoglobin. In addition, statistical differences were detected in the onset age as well as the biochemical indicators, including glycosylated hemoglobin and blood glucose serum protein, along with the difference in the degree of cardiovascular stenosis. CONCLUSIONS: The onset age of CAD was shown to serve as a vital risk factor for ICVD. The primary prevention of ICVD in patients with CAD should lay more emphasis on the management of hypertension and diabetes.

Reviving Static Charts into Live Charts.

Data charts are prevalent across various fields due to their efficacy in conveying complex data relationships. However, static charts may sometimes struggle to engage readers and efficiently present intricate information, potentially resulting in limited understanding. We introduce "Live Charts," a new format of presentation that decomposes complex information within a chart and explains the information pieces sequentially through rich animations and accompanying audio narration. We propose an automated approach to revive static charts into Live Charts. Our method integrates GNN-based techniques to analyze the chart components and extract data from charts. Then we adopt large natural language models to generate appropriate animated visuals along with a voice-over to produce Live Charts from static ones. We conducted a thorough evaluation of our approach, which involved the model performance, use cases, a crowd-sourced user study, and expert interviews. The results demonstrate Live Charts offer a multi-sensory experience where readers can follow the information and understand the data insights better. We analyze the benefits and drawbacks of Live Charts over static charts as a new information consumption experience.

Hierarchical Recognizing Vector Graphics and A New Chart-based Vector Graphics Dataset.

The conventional approach to image recognition has been based on raster graphics, which can suffer from aliasing and information loss when scaled up or down. In this paper, we propose a novel approach that leverages the benefits of vector graphics for object localization and classification. Our method, called YOLaT (You Only Look at Text), takes the textual document of vector graphics as input, rather than rendering it into pixels. YOLaT builds multi-graphs to model the structural and spatial information in vector graphics and utilizes a dual-stream graph neural network (GNN) to detect objects from the graph. However, for real-world vector graphics, YOLaT only models in flat GNN with vertexes as nodes ignore higher-level information of vector data. Therefore, we propose YOLaT++ to learn Multi-level Abstraction Feature Learning from a new perspective: Primitive Shapes to Curves and Points. On the other hand, given few public datasets focus on vector graphics, data-driven learning cannot exert its full power on this format. We provide a large-scale and challenging dataset for Chart-based Vector Graphics Detection and Chart Understanding, termed VG-DCU, with vector graphics, raster graphics, annotations, and raw data drawn for creating these vector charts. Experiments show that the YOLaT series outperforms both vector graphics and raster graphics-based object detection methods on both subsets of VG-DCU in terms of both accuracy and efficiency, showcasing the potential of vector graphics for image recognition tasks. Our codes, models, and the VG-DCU dataset are available at: https://github.com/microsoft/YOLaT-VectorGraphicsRecognition.

Esketamine enhances memory reconsolidation in the novel object recognition task.

Esketamine, the right-handed optical isomer of racemic ketamine, is a rapidly acting antidepressant approved by the FDA for treatment-resistant depression in 2019. However, few studies have investigated esketamine's role in learning and memory, particularly in the context of memory reconsolidation. Herein, we evaluated esketamine's role in memory reconsolidation in 7-week-old male Institute of Cancer Research mice subjected to the novel object recognition (NOR) memory task. The NOR reconsolidation procedure comprised three phases: sampling, reactivation, and testing. Esketamine-enhanced NOR memory performance when injected into mice 0 h after reactivation rather than following a 6 h delay. Conversely, administering esketamine 24 h after sampling without reactivation did not enhance NOR memory performance. Notably, esketamine exhibited no discernible effects on nonspecific responses, such as locomotor activity and exploratory behavior. Furthermore, the α-amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor antagonist NBQX effectively blocked the esketamine-induced enhancement of memory reconsolidation. In conclusion, esketamine treatment markedly improves memory reconsolidation in NOR tasks, and this effect is linked to AMPA receptor activity.

Kindergarten Visual-Perceptual and Motor Skills and Behavioral Traits Predict First-Grade Chinese Handwriting Legibility and Speed.

IMPORTANCE: Clarifying the relationship between kindergarteners' characteristics and their future handwriting performance is beneficial for the early detection of children at risk of handwriting difficulties. OBJECTIVE: To determine which visual-perceptual and motor skills and behavioral traits significantly predict kindergartners' Chinese handwriting legibility and speed in the first grade. DESIGN: One-year longitudinal, observational design. SETTING: Kindergarten and elementary schools. PARTICIPANTS: One hundred six kindergarten children (53 boys and 53 girls; ages 5 or 6 yr) were recruited. OUTCOMES AND MEASURES: The participants completed two subtests of the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition, Test of Visual Perceptual Skills-Third Edition, Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery™ VMI), and the Attention-Deficit/Hyperactivity Disorder Test-Chinese Version in kindergarten. Their handwriting legibility (character accuracy and construction) and speed were assessed by investigator-developed Chinese handwriting tests in the first grade. RESULTS: Multivariate regression analyses indicated the independent predictive power of spatial relationships (p = .042) and inattention (p = .004) for character accuracy. Visual-motor integration (VMI; p = .008) and inattention (p = .002) were the key predictors of character construction. Manual dexterity (p = .001) was the only significant predictor of writing speed. CONCLUSIONS AND RELEVANCE: Kindergarteners who perform poorly in spatial relationships, VMI, manual dexterity, and attention are likely to have less legible Chinese handwriting and slow writing speed in first grade. Plain-Language Summary: Children's visual-perceptual and motor skills and behavioral traits in kindergarten can predict their Chinese handwriting legibility and speed in first grade. This study found that kindergarteners who performed poorly in spatial relationships, VMI, manual dexterity, and attention were likely to have less legible Chinese handwriting and slow writing speed in the first grade.

Two new bibenzyl methylglucosides as SIRT3 activators obtained through microbial transformation.

Microbial transformation of dihydroresveratrol (DHRSV) using Beauveria bassiana has produced two new methylglucosylated derivatives of DHRSV (1 and 2), whose structures were characterized as 4'-O-(4″-O-methyl-ß-D-glucopyranosyl)-dihydroresveratrol (4'-O-MG DHRSV, 1) and 3-O-(4″-O-methyl-ß-D-glucopyranosyl)-dihydroresveratrol (3-O-MG DHRSV, 2) on the basis of spectroscopic methods. They showed moderate SIRT3 agonistic activity, and compound 2 exhibited the best deacetylation of 406.63% at 10 µM. The activity of 2 increased by 3.12-fold compared with that of DHRSV, since 2 performed better in molecular docking assay (GScore -8.445).

Content measurement of doxorubicin hydrochloride and lonidamine by HPLC / 药学实践杂志

Objective To establish a method for the simultaneous determination of DOX·HCl and LND. Methods HPLC was performed on Agilent 5 HC-C18（2） （4.6 mm × 250 mm, 5 µm） column. The mobile phase was methanol-0.1% TFA aqueous solution, and the gradient elution procedure were: 0 to 3 min, 65% methanol; 3 to 7 min, 65%→90% methanol; 7 to 13 min, 90% methanol; 13 to 15 min, 90%→65% methanol; 15 to 20 min, 65% methanol. The collection time was 20 min, the balance time was 3 min, the UV detection wavelengths were 205 nm and 253 nm. The flow rate was 1.0 ml/min and the column temperature was 35℃. The amount of inlet was 10 µl. Results The method was highly specific, and both DOX·HCl and LND exhibited good linearity in the concentration range of 1-40 µg/ml and 6-240 µg/ml, respectively. The two compounds’ precision, stability, and recovery satisfied the requirements of the method. Conclusion This study established a HPLC method that was suitable for the simultaneous detection of DOX·HCl and LND. This method’s high level of specificity, accuracy, and reliability .

Preparation and pharmacokinetics of flumazenil sublingual tablet / 药学实践杂志

Objective To prepare flumazenil sublingual tablets and study its bioavailability. Methods Flumazenil sublingual tablets were prepared by compressing flumazenil inclusion compound with hydroxypropyl-β-cyclodextrin as the inclusion material. In a double-cycle crossover trial, twelve beagle dogs were randomly divided into two groups, one group receiving flumazenil sublingual tablets and the other receiving flumazenil injections. LC-MS method was developed and validated to determine flumazenil plasma concentration. The pharmacokinetic parameters and bioavailability were calculated using WinNonlin pharmacokinetic software. Results In the pharmacokinetic study, AUClast of flumazenil injection and sublingual tablet was （8.41±2.15） and （8.86±2.83） h·ng·ml−1, respectively; Cmax was （10.96±2.62） and （6.36±2.14） ng/ml, respectively; tmax was （0.18±0.05） and （0.58±0.24） h, respectively. The bioavailability of flumazenil sublingual tablet was 52.68%. Conclusion Clathrates were used to prepare flumazenil sublingual tablets to achieve safe and efficient delivery. LC-MS method was established for the determination of flumazenil plasma concentration, and the advantages were simple, accurate and sensitive.

Research progress on clinical application and quality control of sprays / 药学实践杂志

Sprays have gained significant attention and widespread use due to their numerous advantages, including rapid action, safety, and convenience. They are widely used in various fields such as dermatology, respiratory disease treatment, wound repair, and central nervous system targeted drug delivery. With the in-depth research of new drugs and modern pharmaceutics, the development ideas of sprays are more diverse, and the application scenarios are increasingly extensive. In this review the clinical application status of sprays and the latest research progress were summarized. Then the quality control parameters were briefly introduced，which provided reference for the research and development of sprays.

Isolation of bone marrow mesenchymal stem cells in transgenic pigs and co-culture with porcine islets / 器官移植

Objective To investigate the isolation and culture of porcine bone marrow mesenchymal stem cell (BMSC) with α-1, 3-galactosyltransferase (GGTA1) gene knockout (GTKO), GTKO/ human CD46 (hCD46) insertion and cytidine monopho-N-acetylneuraminic acid hydroxylase (CMAH)/GGTA1 gene knockout (Neu5GC/Gal), and the protective effect of co-culture with porcine islets on islet cells. Methods Bone marrow was extracted from different transgenic pigs modified with GTKO, GTKO/hCD46 and Neu5GC/Gal. Porcine BMSC were isolated by the whole bone marrow adherent method and then cultured. The morphology of BMSC was observed and the surface markers of BMSC were identified by flow cytometry. Meantime, the multi-directional differentiation induced by BMSC was observed, and the labeling and tracing of BMSC were realized by green fluorescent protein (GFP) transfection. The porcine BMSC transfected with GFP were co-cultured with porcine islet cells. Morphological changes of porcine islet cells were observed, and compared with those in the porcine islet cell alone culture group. Results BMSC derived from pigs were spindle-shaped in vitro, expressing biomarkers of CD29, CD44, CD73, CD90, CD105 and CD166 rather than CD34 and CD45. These cells were able to differentiate into adipocytes, osteoblasts and chondrocytes. Porcine BMSC with GFP transfection could be labeled and traced, which could be stably expressed in the daughter cells after cell division. Porcine BMSC exerted certain protective effect on islet cells. Conclusions GFP-labeled porcine BMSC modified with GTKO, GTKO/hCD46 and Neu5GC/Gal are successfully established, which exert certain protective effect upon islet cells.

A real-world case-control study on the efficacy and safety of pulsed field ablation for atrial fibrillation.

OBJECTIVE: The primary objective of this study was to evaluate the efficacy and safety of pulsed field ablation in individuals diagnosed with atrial fibrillation. METHODS: A total of 36 patients diagnosed with atrial fibrillation were enrolled in the pulsed field ablation group, while another 36 patients diagnosed with atrial fibrillation were included in the radiofrequency ablation group. Among the study participants, 15 patients in the pulsed field ablation group and 17 patients in the radiofrequency ablation group had persistent atrial fibrillation. Comprehensive comparisons were made between the two groups, including baseline data, underlying diseases, medication usage, intraoperative parameters, and atrial fibrillation recurrence rates at 1, 3, and 6 months during the postoperative follow-up period. RESULTS: (1) There were no significant differences observed between the two groups concerning baseline data and antiarrhythmic drug usage (P > 0.05); (2) the effective ablation time for both left and right pulmonary veins in the pulsed field ablation group was markedly shorter compared to the radiofrequency ablation group (P < 0.001 for each vein); (3) within the pulsed field ablation group, the number of discharges, catheter operation time, and effective ablation time for the left pulmonary vein were significantly higher than those for the right pulmonary vein (P < 0.05). Conversely, in the radiofrequency ablation group, the number of discharges for the left pulmonary vein was significantly higher than that for the right pulmonary vein (P < 0.05); and (4) when comparing sinus rhythm maintenance at 1, 3, and 6 months postoperatively, no statistically significant differences were noted between the two groups for paroxysmal, persistent, and paroxysmal + persistent atrial fibrillation cases (P > 0.05). CONCLUSION: During the 6-month follow-up period, pulsed field ablation demonstrated comparable efficacy to radiofrequency ablation with respect to recurrence rates for both paroxysmal and persistent atrial fibrillation. Moreover, pulsed field ablation exhibited high safety levels, excellent surgical efficiency, and a notably brief learning curve, affirming its viability as a therapeutic option for these conditions.

[Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease].

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-ß1(TGF-ß1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

[Phage antibody library technology in tumor therapy: a review].

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.

[Research progress in pathogenesis and traditional Chinese medicines treatment of ischemic stroke-related headache].

Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

The Addition of an Ultra-Small Amount of Black Phosphorous Quantum Dots Endow Self-Healing Polyurethane with a Biomimetic Intelligent Response.

This study explores new applications of black phosphorus quantum dots (BPQDs) by adding them to self-healing material systems for the first time. Self-healing polyurethane with an ultra-small amount of BPQDs has biomimetic intelligent responsiveness and achieves balance between its mechanical and self-healing properties. By adding 0.0001 wt% BPQDs to self-healing polyurethane, the fracture strength of the material increases from 3.0 to 12.3 MPa, and the elongation at break also increases from 750% to 860%. Meanwhile, the self-healing efficiency remains at 98%. The addition of BPQDs significantly improves the deformation recovery ability of the composite materials and transforms the surface of self-healing polyurethane from hydrophilic to hydrophobic, making it suitable for applications in fields such as electronic skin and flexible wearable devices. This study provides a simple and feasible strategy for endowing self-healing materials with biomimetic intelligent responsiveness using a small amount of BPQDs.

Medicarpin suppresses proliferation and triggeres apoptosis by upregulation of BID, BAX, CASP3, CASP8, and CYCS in glioblastoma.

Glioblastoma (GBM) is the most malignant brain tumor and incurable. Medicarpin (MED), a flavonoid compound from the legume family, has multiple targets and anticancer properties. However, the role of MED in GBM remains unclear. The objective of this study was to explore the effects of MED on the apoptosis of GBM and to explain the potential molecular mechanisms. We found that the IC50 values of U251 and U-87 MG cells treated with MED for 24 h were 271 µg/mL and 175 µg/mL, and the IC50 values for 48 h were 154 µg/mL and 161 µg/mL, respectively. Additionally, the cell cycle of U251 and U-87 MG cells were arrested at the G2/M phase. Furthermore, the apoptosis rate of U251 and U-87 MG cells increased from 6.26% to 18.36% and 12.46% to 31.33% for 48 h, respectively. The migration rate of U251 and U-87 MG decreased from 20% to 5% and 25% to 15% for 12 h and these of U251 and U-87 MG decreased from 50% to 28% and 60% to 25% for 24 h. MED suppressed GBM tumorigenesis, and improved survival rate of tumor-bearing mice. Taken together, MED triggered GBM apoptosis through upregulation of pro-apoptotic proteins (BID, BAX, CASP3, CASP8, and CYCS), showed strong inhibitory effects on cell proliferation and cell migration, and displayed anti-tumor activity in nude mice.

[Effect and mechanism of Dahuang Zhechong Pills in improving liver aging in rats by regulating ROS-mediated PI3K/Akt/FoxO4 signaling pathway].

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.

The effect of green coffee extract supplementation on obesity indices: critical umbrella review of interventional meta-analyses.

Despite a multitude of investigations assessing the impact of green coffee extract supplementation on obesity indices, there is still a great deal of heated debate regarding the benefits of this intervention in obesity management. Therefore, in order to clarify the effect of green coffee extract on waist circumference (WC), body mass index (BMI) and body weight (BW), we conducted an umbrella review of interventional meta-analyses. The Web of Science, Scopus, PubMed/Medline, and Embase databases were searched using specific keywords and word combinations. The umbrella meta-analysis was performed using the Stata software version 17 (Stata Corp. College Station, Texas, USA). We pooled effect sizes (ES) and confidence intervals (CI) for the outcomes using the random effects model (the DerSimonian and Laird method). In total, 5 eligible meta-analyses were included in the final quantitative assessment. Data pooled from 5 eligible papers revealed that green coffee extract can reduce BW (WMD: -1.22 kg, 95% CI: -1.53 to -0.92, p < 0.001), BMI (WMD: -0.48 kg/m2, 95% CI: -0.67 to -0.29, p < 0.001) and WC (WMD: -0.55 cm, 95% CI: -0.80 to -0.31, p < 0.001). Subgroup analyses highlighted that green coffee extract supplementation in dosages ≤600 mg/day and interventions lasting >7 wk are more likely to decrease BW. The present umbrella meta-analysis confirms the beneficial effects of green coffee extract in reducing WC, BMI, and BW. Thus, we may infer that green coffee extract can be used as a complementary therapy in the management of obesity.