Preparation and characterization of carboxymethylated Anemarrhena asphodeloides polysaccharide and its effect on the gelatinization of wheat starch.

In this study, a carboxymethylated Anemarrhena asphodeloides polysaccharide (CM-AARP) with an molecular weight (Mw) of 7.8 × 104 Da was obtained. CM-AARP was composed of four monosaccharides including d-mannose, d-glucose, d-galactose, and l-arabinose. Nuclear magnetic resonance (NMR) spectra revealed that the skeleton of CM-AARP was identical to that of AARP. Compared with AARP, CM-AARP had a superior inhibition effect on the gelatinization of wheat starch (WS) under the same condition. The addition of CM-AARP and AARP at 12 % enhanced the gelatinization temperature (60.47 ± 1.30 °C) of WS to 73.88 ± 0.49 °C and 69.75 ± 0.52 °C, respectively. CM-AARP could maintain the crystal structure of WS during gelatinization, the relative crystallinity with the 12 % CM-AARP addition was determined as 29.18 % ± 1.49 %, exceeding that of pure WS at 21.96 % ± 0.66 %. Moreover, CM-AARP influenced the rheological behavior of the gelatinized WS by reducing the viscosity and improving the fluidity. The results suggested that CM-AARP played an essential role in starch gelatinization and was a potential stabilizer in the starch-based food industry.

The activity of hyaD contributed to the virulence of avian Pasteurella multocida.

Fowl cholera is an infectious disease that affects both poultry and wild birds, characterized by hemorrhagic and septicemic symptoms, caused by Pasteurella multocida (P. multocida), and leading to substantial economic losses in the poultry sector. The development of genetic engineering vaccines against avian P. multocida encountered early-stage challenges due to the limited availability of effective gene editing tools. Presently, NgAgoDM-enhanced homologous recombination stands as a potent technique for achieving efficient gene knockout in avian P. multocida. Hence, this study employed NgAgoDM-enhanced homologous recombination to target and knockout hyaE (239-359aa), hyaD, hexABC, and hexD, denoted as ΔhyaE (239-359aa), ΔhyaD, ΔhexABC, and ΔhexD, respectively. Additionally, we generated a hyaD recovery strain with two point mutations, designated as mhyaD. Thus, this study systematically examined the impact of capsular synthetic gene clusters on the pathogenicity of P. multocida. Moreover, the study demonstrated the critical role of hyaD activity in the virulence of avian P. multocida. This study offers novel insights for enhancing attenuated vaccines further.

Wogonin protects against bleomycin-induced mouse pulmonary fibrosis via the inhibition of CDK9/p53-mediated cell senescence.

Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently with few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be a potential therapeutic target. Emerging evidence suggests wogonin, the bioactive compound isolated from Scutellaria baicalensis, owns the anti-senescence properties, however, the possible impact of wogonin on PF and the potential mechanisms remain unclear. In this study, a well-established mouse model of PF was utilized which mice were administrated with bleomycin (BLM). Strikingly, wogonin treatment significantly reduced fibrosis deposition in the lung induced by BLM. In vitro, wogonin also suppressed fibrotic markers of cultured epithelial cells stimulated by BLM or hydrogen peroxide. Mechanistic investigation revealed that wogonin attenuated the expressions of DNA damage marker γ-H2AX and senescence-related markers including phosphorylated p53, p21, retinoblastoma protein (pRB), and senescence-associated ß-galactosidase (SA-ß-gal). Moreover, wogonin, as a direct and selective inhibitor of cyclin-dependent kinase 9 (CDK9), exhibited anti-fibrotic capacity by inhibiting CDK9 and p53/p21 signalling. In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.

A thorough investigation into the correlation between migraines and the gut microbiome: an in-depth analysis using Mendelian randomization studies.

Objective: A growing body of evidence underscores a significant association between neurological disorders, particularly migraines, and the gut microbiota. However, a research gap persists in understanding the cause-and-effect dynamics between these elements. Therefore, we employed robust methodologies aimed at thoroughly exploring the causal relationship between the gut microbiome and migraines. Methods: Employing bidirectional Two Sample Mendelian Randomization (TSMR) analysis, we investigated the causal association between the composition of the gut microbiota and migraines. Data summarizing the relationship between gut microbiota and migraines were extracted from one or more genome-wide association studies. The TSMR analysis employed five methods to assess the correlation between the gut microbiota and migraines, with the inverse variance-weighted method serving as the primary approach for analyzing causal links. Sensitivity analyses were applied to address horizontal pleiotropy and heterogeneity. Simultaneously, a meta-analysis was performed to strengthen the robustness of the findings. Additionally, a reverse TSMR was carried out to explore potential occurrences of reverse causal relationships. Results: The ongoing TSMR analysis identified a collection of 14 bacterial taxa connected to migraines. Among these, 8 taxa exhibited a protective effect, while 5 taxa had a detrimental impact, and 1 taxon maintained a neutral relationship. The reverse Mendelian randomization analysis highlighted stable outcomes for only one bacterial taxonomic group. Conclusion: The study confirms a causal relationship between the gut microbiota and migraines, offering a new perspective for migraine research. Strategically targeting specific bacterial taxa with dysregulation may be effective in both preventing and treating migraines, thus opening new avenues for therapeutic strategies.

Creep Failure Characteristics and Mathematical Modeling of High-Density Polyethylene Geomembranes under High Stress Levels.

To explore the creep characteristics of geomembrane under different tensile stresses, a series of creep tests were carried out on high-density polyethylene (HDPE) geomembrane specimens. For the interpretation and fitting of the experimental data, refined approximation functions were proposed. Particular attention was paid to the creep failure behavior under high tensile stresses, i.e., 70%, 80%, and 90% of maximum peak stress. To investigate the effects of size on the mechanical response, experiments with two different membrane thicknesses were conducted. The results obtained under high stress levels were compared with creep tests at medium and low stress levels. Depending on load level, different creep characteristics can be distinguished. In the secondary creep state, the creep velocity is higher for higher load levels. In contrast to the medium and low load levels, the geomembrane under high stresses underwent the tertiary creep stage after instantaneous deformation and primary and secondary creep stages. In some tests, it was observed that under very high stress levels, creep velocity does not necessarily follow the expected trend and creep rupture can occur within a short time. For numerical simulation, an improved mathematical model was proposed to reproduce in a unified manner the experimental data of the whole non-linear evolution of creep elongation under different stress levels.

Innovative hybrid strategy for quality improvement of Goji tea: ultrasonic-ethyl oleate pretreatment combined with heat pump drying.

BACKGROUND: Goji berries, renowned for their nutritional benefits, are traditionally dried to extend shelf life and preserve quality. However, conventional drying methods often result in uneven drying, color loss and reduced rehydration capacity. This study investigates an innovative hybrid strategy combining ultrasonic-ethyl oleate (US+AEEO) pretreatment with heat pump drying (HPD) to enhance the drying process of Goji berries. RESULTS: Fresh Goji berries underwent US+AEEO pretreatment, which significantly disrupted the waxy layer, enhancing drying efficiency and water infiltration during rehydration. Compared to freeze drying (FD), HPD combined with US+AEEO pretreatment resulted in higher retention of total polyphenol content (TPC) and total flavonoid content (TFC) in the Goji soaking soup. Specifically, the HPD-US+AEEO samples exhibited the highest TPC and TFC levels, significantly outperforming FD samples. Additionally, the DPPH and ABTS antioxidant assays demonstrated higher scavenging activities in HPD-US+AEEO samples. The rehydration kinetics revealed that HPD samples had a superior rehydration rate and final moisture content compared to FD samples. Low-field nuclear magnetic resonance and magnetic resonance imaging analyses confirmed enhanced water distribution and higher mobility in HPD-US+AEEO samples. Scanning electron microscopy indicated a more porous structure in US+AEEO-treated samples, facilitating better water absorption and functional component retention. CONCLUSION: The combination of US+AEEO pretreatment with HPD significantly improves the drying process of Goji berries, enhancing nutrient retention, color preservation and rehydration properties. This innovative drying method offers a promising solution for producing high-quality dried Goji berries, benefiting both the food industry and health-conscious consumers. © 2024 Society of Chemical Industry.

Effectiveness of the six-step approach guided online training program to improve knowledge of Mycoplasma pneumoniae pneumonia among pediatricians: a pretest-posttest study.

Background: In 2023, China witnessed an earlier and more widespread outbreak of Mycoplasma pneumoniae pneumonia (MPP). To address this situation, an online training program was designed to enhance the knowledge of MPP among pediatricians in Shanghai, China. Methods: An online training program on the diagnosis and treatment of MPP, guided by Kern's six-step approach, was developed by the Shanghai Pediatric Clinical Quality Control Center. A pre- and post-training survey was conducted using a 20-item self-administered questionnaire to investigate the pediatricians' knowledge of MPP. A linkage mechanism was established to match pretest/posttest questionnaires using personal identifiers. Paired t-tests and McNemar tests were performed to measure the differences, as appropriate, between pre- and post-training groups. A higher survey score indicated better knowledge. Results: There were 289 participants performed pre- and post-tests. The average age of the respondents was 38.7 years (standard deviation: 8.9). Over 80% of the participants were primary (32.5%) and intermediate (47.8%) pediatricians. Those from specialized hospitals accounted for the highest proportion (41.5%). The post-training group achieved significantly higher total scores than the pre-training group (91.3 vs. 67.7, t=22.48, P<0.001), regardless of the professional titles or hospital levels (all P<0.001). The accuracy rates of each question increased significantly in the post-training group (all P<0.001). Conclusions: The online training program effectively enhanced pediatricians' understanding of diagnosing and treating MPP. It is recommended to maintain continuous education and training targeting all healthcare providers.

Functional properties, structural characteristics, and anti-complementary activities of two degraded polysaccharides from strawberry fruits.

Two low-molecular-weight polysaccharides (DPSP50 and DPSP70) were obtained using hydrogen peroxide-vitamin C (H2O2-Vc) treatment at 50 °C and 70 °C, respectively. Both DPSP50 and DPSP70 comprised the same six monosaccharides in different ratios, and their molecular weights (Mws) were 640 kDa and 346 kDa, respectively. Functional properties analyses demonstrated that DPSP50 and DPSP70 each had an excellent water holding capacity, oil absorption capacity, and emulsion properties, as well as shear-thinning characteristics and viscoelastic properties. Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopic assays confirmed the existence of α-, ß-pyranose rings and the same six sugar residues in DPSP50 and DPSP70. The results of Congo red test, scanning electron microscopy (SEM), and X-ray diffraction (XRD) demonstrated that DPSP50 and DPSP70 did not contain triple-helix conformations, but were amorphous aggregates with flake-like shape and rough surface. Additionally, both DPSP50 and DPSP70 showed strong anti-complementary activities through the classical pathway and the alternative pathway. The results support the potential utility of these degraded polysaccharides from strawberry fruits in functional foods and medicines.

Polyphyllin I alleviates neuroinflammation after cerebral ischemia-reperfusion injury via facilitating autophagy-mediated M2 microglial polarization.

Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia-reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia-reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia-reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

Risk Factors for Urinary Tract Infection in Elderly Patients with Type 2 Diabetes: A Retrospective Cohort Study.

OBJECTIVE: The risk factors of urinary tract infection in elderly patients with type 2 diabetes were investigated. METHODS: A total of 72 elderly patients admitted to our hospital from December 2019 to September 2023 because of with type 2 diabetes were retrospectively included. They were divided into the observation group (n = 35) and control group (n = 37) according to whether they had urinary tract infection. The general clinical data, clinical characteristics and the distribution of pathogenic bacteria in the observation group were collected and analysed. Then, t-tests, chi-square tests, regression analysis and receiver operating characteristic curve analysis were conducted. RESULTS: Escherichia coli (E. coli) accounted for 51.43% of the pathogenic bacteria in the observation group, whereas Klebsiella pneumoniae (K. pneumoniae) accounted for 22.86%. The remaining pathogens accounted for 2.86% each. Differences in gender, course of disease, glycosylated haemoglobin and comorbid urinary calculi were found between the groups (p < 0.05); These factors were all risk factors for concurrent urinary infection, and the odds ratios were all >1. The obtained values for gender, disease course, glycosylated haemoglobin and comorbid urinary calculi were respectively 0.594, 0.654, 0.738 and 0.696 (area under the curve); 0.971, 0.714, 0.800 and 0.743 (sensitivity); 0.216, 0.595, 0.676 and 0.649 (specificity); And 0.188, 0.309, 0.476 and 0.392 (Youden index). CONCLUSIONS: Common pathogens in elderly people with type 2 diabetes and comorbid urinary tract infection are E. coli and K. pneumoniae. Risk factors include gender, disease duration, glycosylated haemoglobin and urinary stones. The prompt identification of pathogens and risk factors facilitates clinical treatment, reducing infection incidence.

Investigating the regional ecological environment stability and its feedback effect on interference using a novel vegetation resilience assessment model.

Vegetation resilience is critical for understanding the dynamic feedback effect of regional ecological environment stability against interferences. Thus, based on quantify the interferences of climate dryness and vegetation water deficit affecting vegetation growth function, incorporate mechanical Hooke's law to develop a vegetation resilience assessment model by quantitatively expressing vegetation growth function maintenance ability, to reveal the ecological environment stability and its feedback effect on interferences in the study area. The essential discoveries of the study are as follows: (1) with the increase of precipitation and the improvement of afforestation on soil erosion, the interferences intensity of climate dryness and vegetation water deficit in the ecological environment decreased by 5.88 % and 4.92 % respectively, the regional vegetation growth function loss was improved, especially in the southern region; (2) the decrease of vegetation growth function loss promoted the vegetation resilience level fluctuated from class II to class IV, with the average annual vegetation resilience increased by 7.02 %, reflecting that the regional ecological environment stability increased from difficult to rapid recovery after disturbance, and the benefit was especially noticeable in the eastern and southern forested areas; (3) the contribution rates of climate dryness and vegetation water deficit to the variation of vegetation resilience caused by vegetation restoration were -1.38 % and 4.73 %, respectively, and the prominent positive feedback effect of increasing vegetation resilience with decreasing vegetation water deficit degree in forest restoration area, indicating that the vegetation water deficit greatly impacts ecological environment stability in the study area, and forest restoration constantly improves regional ecological environment stability more than grassland restoration. This research has crucial guiding implications for supporting the sustainable development of regional ecological environments.

2D MoB MBene: An Efficient Co-Catalyst for Photocatalytic Hydrogen Production under Visible Light.

Highly active and low-cost co-catalysts have a positive effect on the enhancement of solar H2 production. Here, we employ two-dimensional (2D) MBene as a noble-metal-free co-catalyst to boost semiconductor for photocatalytic H2 production. MoB MBene is a 2D nanoboride, which is directly made from MoAlB by a facile hydrothermal etching and manual scraping off process. The as-synthesized MoB MBene with purity >95 wt % is treated by ultrasonic cell pulverization to obtain ultrathin 2D MoB MBene nanosheets (∼0.61 nm) and integrated with CdS via an electrostatic interaction strategy. The CdS/MoB composites exhibit an ultrahigh photocatalytic H2 production activity of 16,892 µmol g-1 h-1 under visible light, surpassing that of pure CdS by an exciting factor of ≈1135%. Theoretical calculations and various measurements account for the high performance in terms of Gibbs free energy, work functions, and photoelectrochemical properties. This work discovers the huge potential of these promising 2D MBene family materials as high-efficiency and low-cost co-catalysts for photocatalytic H2 production.

Integrated Exploration of Epigenetic Dysregulation Reveals a Stemness/EMT Subtype and MMP12 Linked to the Progression and Prognosis in Hepatocellular Carcinoma.

Epigenetic dysregulation drives aberrant transcriptional programs playing a critical role in hepatocellular carcinoma (HCC), which may provide novel insights into the heterogeneity of HCC. This study performed an integrated exploration on the epigenetic dysregulation of miRNA and methylation. We discovered and validated three patterns endowed with gene-related transcriptional traits and clinical outcomes. Specially, a stemness/epithelial-mesenchymal transition (EMT) subtype was featured by immune exhaustion and the worst prognosis. Besides, MMP12, a characteristic gene, was highly expressed in the stemness/EMT subtype, which was verified as a pivotal regulator linked to the unfavorable prognosis and further proven to promote tumor proliferation, invasion, and metastasis in vitro experiments. Proteomic analysis by mass spectrometry sequencing also indicated that the overexpression of MMP12 was significantly associated with cell proliferation and adhesion. Taken together, this study unveils innovative insights into epigenetic dysregulation and identifies a stemness/EMT subtype-specific gene, MMP12, correlated with the progression and prognosis of HCC.

Effect of ethanol addition on the physicochemical, structural and in vitro digestive properties of Tartary buckwheat starch-quercetin/rutin complexes.

The effects of ethanol on the physicochemical, structural and in vitro digestive properties of Tartary buckwheat starch-quercetin/rutin complexes (e-TBSQ and e-TBSR) were investigated. Ethanol restricted the gelatinization of Tartary buckwheat starch (TBS), which resulted an increase in ∆H, G' and G" as well as a decrease in apparent viscosity of e-TBSQ and e-TBSR. The particle size, scanning electron microscopy and X-ray diffraction results showed that ethanol influenced the morphological structure of TBS granules and the starch crystalline structure in e-TBSQ and e-TBSR changed from B-type to V-type when the ethanol concentration was 25%. Saturation transfer difference-nuclear magnetic resonance results revealed that ethanol weakened the binding ability of quercetin/rutin to TBS in e-TBSQ and e-TBSR, leading to a change in the binding site on the quercetin structural unit. The residual ungelatinized TBS granules in e-TBSQ and e-TBSR induced a high slowly digestible starch content, and thus displayed a "resistant-to-digestion".

Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype-phenotype correlations. METHODS: Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype-phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population. RESULTS: Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad. CONCLUSIONS: We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.

New species, new records and common species of Pluteussect.Celluloderma from northern China.

Wood-rotting fungi are organisms that can decompose wood substrates and extract nutrients from them to support their growth. They play a crucial role in the material cycle of forest ecosystems. The genus Pluteus plays a significant role in wood decomposition. In this study, the morphology and molecular systematics of the sect. Celluloderma of the genus Pluteus were carried out. Pluteusbrunneodiscus was identified as a new species, along with the discovery of two new records, P.cystidiosus and P.chrysophlebius, and a common species, P.romellii. Pluteusbrunneodiscus is characterized by the brown center of the pileus that transitions to white towards the margins, with the surface cracking to form irregular granules. It is typically found in Populus forests growing on decomposing twigs or wood chips. Line drawings, color photographs, and phylogenetic analyses of related species within the genus Pluteus accompany the descriptions of these four species. The analyses are based on ITS + TEF1-α sequence data. Finally, a key for the twenty species within the sect. Celluloderma of the genus Pluteus, which has been documented in China, is provided.

Effects of Freeze-Thaw Cycles on the Quality of a Novel Mixed Grain Composite Dough and Its Product (Potato-Oat Yu): Hybridization of Potatoes and Oats.

To provide a theoretical basis for the frozen storage of potato-oat composite dough and its products, this investigation examines changes in the quality of potato-oat composite dough and its resulting product during freeze-thaw cycles. The study measured key aspects such as moisture content, dynamic rheological properties, water state, protein secondary structure, color, and sensory assessment. The influence of these factors on the product's quality is analyzed. The findings revealed that the freeze-thaw treatment caused a reduction in water content, freezable water, and deeply bound water, as well as an increase in weakly bound water, ß-sheet, random coil, and α-helix, and a decreased ß-turn of the potato-oat composite dough. Additionally, the dough treated by freeze-thaw cycles resulted in darker color, and the sensory properties of the product were affected significantly after exceeding three freeze-thaw cycles. Moreover, an increase in the number of freeze-thaw cycles resulted in an upward trend of moisture content for the composite dough, whereas G' initially increased and then decreased. The G″ of the composite dough peaked after the third freeze-thaw cycle. Overall, the composite dough quality significantly deteriorated at the fourth freeze-thaw cycle. There was a significant increase in the freezable water content, the largest modulus of elasticity, and the smallest tan δ. Therefore, the usage of the potato-oat composite dough should not exceed three cycles.

Machine learning-driven diagnostic signature provides new insights in clinical management of hypertrophic cardiomyopathy.

AIMS: In an era of evolving diagnostic possibilities, existing diagnostic systems are not fully sufficient to promptly recognize patients with early-stage hypertrophic cardiomyopathy (HCM) without symptomatic and instrumental features. Considering the sudden death of HCM, developing a novel diagnostic model to clarify the patients with early-stage HCM and the immunological characteristics can avoid misdiagnosis and attenuate disease progression. METHODS AND RESULTS: Three hundred eighty-five samples from four independent cohorts were systematically retrieved. The weighted gene co-expression network analysis, differential expression analysis (|log2(foldchange)| > 0.5 and adjusted P < 0.05), and protein-protein interaction network were sequentially performed to identify HCM-related hub genes. With a machine learning algorithm, the least absolute shrinkage and selection operator regression algorithm, a stable diagnostic model was developed. The immune-cell infiltration and biological functions of HCM were also explored to characterize its underlying pathogenic mechanisms and the immune signature. Two key modules were screened based on weighted gene co-expression network analysis. Pathogenic mechanisms relevant to extracellular matrix and immune pathways have been discovered. Twenty-seven co-regulated genes were recognized as HCM-related hub genes. Based on the least absolute shrinkage and selection operator algorithm, a stable HCM diagnostic model was constructed, which was further validated in the remaining three cohorts (n = 385). Considering the tight association between HCM and immune-related functions, we assessed the infiltrating abundance of various immune cells and stromal cells based on the xCell algorithm, and certain immune cells were significantly different between high-risk and low-risk groups. CONCLUSIONS: Our study revealed a number of hub genes and novel pathways to provide potential targets for the treatment of HCM. A stable model was developed, providing an efficient tool for the diagnosis of HCM.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

Liraglutide prevents cellular senescence in human retinal endothelial cells (HRECs) mediated by SIRT1: an implication in diabetes retinopathy.

Diabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM. However, the effects of Liraglutide on DR are less reported. Here, we investigated whether treatment with Liraglutide has beneficial effects on high glucose (HG)-induced injury in human retinal microvascular endothelial cells (HRECs). First, we found that exposure to HG reduced the expression of glucagon-like peptide 1 receptor 1 (GLP-1R). Additionally, Liraglutide ameliorated HG-induced increase in the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin 6 (IL-6). Importantly, Liraglutide ameliorated cellular senescence and increased telomerase activity in HG-challenged HRECs. Liraglutide also reduced the levels of p53 and p21. Mechanistically, Liraglutide restored the expression of SIRT1 against HG. In contrast, the knockdown of SIRT1 abolished the protective effects of Liraglutide in cellular senescence of HRECs. Our findings suggest that Liraglutide might possess a benefit on DR mediated by SIRT1.