Optimization and component identification of ultrasound-assisted extraction of functional compounds from waste blackberry (Rubus fruticosus Pollich) seeds.

BACKGROUND: Blackberry seeds, as a by-product of processing, have potential bioactive substances and activities. A response surface method was used to determine the optimal conditions of blackberry seed extracts (BSEs) with high 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity by ultrasound-assisted extraction (UAE). The composition and antioxidant capacity of BSEs were further analyzed. RESULTS: The optimal conditions were material-to-liquid ratio of 0.07 g mL-1, ethanol concentration of 56%, extraction temperature of 39 °C and ultrasonic power of 260 W. Using these conditions, the extraction yield and total polysaccharide, phenolic and anthocyanin contents in BSEs were 0.062 g g-1 and 633.91, 36.21 and 3.07 mg g-1, respectively. The Fourier transform infrared spectra of BSEs exhibited characteristic peaks associated with polysaccharide absorption. The antioxidant capacity, DPPH and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, and ferric reducing antioxidant power of BSEs were 1533.19, 1021.93 and 1093.38 mmol Trolox equivalent g-1, respectively. The delphinidin-3-O-glucoside, paeoniflorin-3-O-glucoside and cyanidin-3-O-arabinoside contents in BSEs were 3.05,12.76 and 1895.90 ± 3.45 µg g-1. Five polyphenols including gallic acid, coumaric acid, ferulic acid, catechin and caffeic acid were identified and quantified in BSEs with its contents at 8850.43, 5053.26, 4984.65, 1846.91 and 192.40 µg g-1. CONCLUSION: These results provide a method for preparing BSE containing functional components such as polysaccharides, phenols and anthocyanins through UAE, and BSEs have potential application in food industries. © 2024 Society of Chemical Industry.

Molecular genetic identification of Wuzhishan ant chicken, a newly discovered resource in China.

Introduction: The Wuzhishan ant (MY) chicken exhibits significant differences from other chicken breeds. However, the molecular genetic relationship between the MY breed and other chicken breeds has not been assessed. Methods: Whole-genome resequencing was used to compare genetic diversity, nucleotide diversity, the fixation index, the linkage disequilibrium coefficient, and phylogenetic tree relationships between the MY breed and the Wenchang (WC), Danzhou (DZ), Bawangling (BW), and Longsheng Feng (LF) breeds. Results: A total of 21,586,378 singlenucleotide polymorphisms and 4,253,341 insertions/deletions were screened out among the five breeds. The MY breed had the second highest genomic genetic diversity and nucleotide diversity and the lowest LD coefficient among the five breeds. Moreover, the phylogenetic tree analysis showed that individual birds of each breed clustered together with those of their respective breeds. Discussion: Our data indicated that the MY breed is distinct from the other breeds and can be considered a new genetic resource.

A three-dimensional quantitative assessment on bony growth and symmetrical recovery of mandible after decompression for unicystic ameloblastoma.

Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann-Whitney U test were used for statistical analysis, with p < 0.05 considered indicative of statistical significance. The mean duration of decompression was 9.41 ± 3.28 months. The mean bone volume increased by 8.07 ± 2.41%, and cortical perforation recovery was 71.97 ± 14.99%. The volumetric symmetry of the mandible improved significantly (p < 0.05), and a statistically significant decrease in AI was observed (p < 0.05). In conclusion, UAM decompression enhances bone growth and symmetry recovery of the mandible. The present evaluation technique is clinically useful for quantitatively assessing mandibular asymmetry.

Is Antibiotic Prophylaxis Reasonable in Parotid Surgery? Retrospective Analysis of Surgical Site Infection.

Background: The prophylactic use of antibiotics in parotid region surgery continues to be a subject of debate. The aim of this study is to elucidate the impact of antibiotic prophylaxis on surgical site infections (SSIs) in parotid region surgery. Patients and Methods: Patients who received antibiotic prophylaxis during the peri-operative period were designated as group 1, whereas those who did not were categorized into group 2. Group 1 cases were further subdivided into three subgroups based on different antibiotic usage patterns. Patient individual information was collected. Clinical data such as surgical duration, post-operative hospital stay, incision infection status, and antibiotic usage were recorded. All data were compared and analyzed among different groups. Results: A total of 357 patients were included in the study, with no statistically significant differences in baseline characteristics. Pre-operative American Society of Anesthesiologists scores did not significantly differ between groups (p = 0.151), but there was a significant distinction in National Nosocomial Infection Surveillance (NNIS) index values (p = 0.044). Furthermore, surgical duration (p = 0.001) and pathology types (p = 0.016) differed significantly. The post-operative hospital stay in group 1 was longer than that in group 2 (p < 0.01). The post-operative SSI rate in group 1 was lower than that in group 2 without statistical significance (2.55% vs. 5.59%, p = 0.141). The logistic regression analysis showed that malignant tumors, longer surgical durations, and higher NNIS index scores correlated positively with post-operative SSI rates. Meanwhile, compared with non-use, all three different antibiotic use modes correlated negatively with SSI occurrence. Conclusions: Antibiotic prophylaxis in parotid gland surgery shows no significant reduction in SSI occurrence. If there is a compelling reason to administer prophylactic antibiotics, pre-operative single dose may be a relatively feasible measure for preventing SSIs.

Prevalence and quantity of lymph nodes at mediastinal stations in patients with lung cancer: lessons from 181 bilateral mediastinal lymphadenectomies.

BACKGROUND: This study evaluated the prevalence and quantity of lymph nodes at particular stations of the mediastinum in patients with lung cancer. These data are important to radiologists, pathologists, and thoracic surgeons because they can serve as a benchmark when assessing the completeness of lymph node dissection. However, relevant data in the literature are scarce. METHODS: Data regarding the number of lymph nodes derived from two randomised trials of bilateral mediastinal lymph node dissection, the BML-1 and BML-2 study, were included in this analysis. Detectable nodes at particular stations of the mediastinum and the number of nodes at these stations were analysed. RESULTS: The mean number of removed nodes was 28.67 (range, 4-88). Detectable lymph nodes were present at stations 2R, 4R, and 7 in 93%, 98%, and 99% of patients, respectively. Nodes were rarely present at stations 9 L (33%), and 3 (35%). The largest number of nodes was observed at stations 7 and 4R (mean, 5 nodes). CONCLUSION: The number of mediastinal lymph nodes in patients with lung cancer may be greater than that in healthy individuals. Lymph nodes were observed at stations 2R, 4R, and 7 in more than 90% of patients with lung cancer. The largest number of nodes was observed at stations 4R and 7. Detectable nodes were rarely observed at stations 3 and 9 L. TRIAL REGISTRATION: ISRCTN 86,637,908.

Far-infrared therapy promotes exercise capacity and glucose metabolism in mice by modulating microbiota homeostasis and activating AMPK.

The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.

Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Ultrasound Shear Wave Elastography Evaluation of the Liver and Implications for Perioperative Medicine.

Ultrasound shear wave elastography (SWE) is a non-invasive, low risk technology allowing the assessment of tissue stiffness. Used clinically for nearly two decades to diagnose and stage liver fibrosis and cirrhosis, it has recently been appreciated for its ability to differentiate between more subtle forms of liver dysfunction. In this review, we will discuss the principle of ultrasound shear wave elastography, its traditional utilization in grading liver cirrhosis, as well as its evolving role in identifying more subtle degrees of liver injury. Finally, we will show how this capacity to distinguish nuanced changes may provide an opportunity for its use in perioperative risk stratification.

[Material basis and mechanism of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" based on UHPLC-Q-Exactive Orbitrap HRMS coupled with network pharmacology and molecular docking].

Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.

FSRW: fuzzy logic-based whale optimization algorithm for trust-aware routing in IoT-based healthcare.

The Internet of Things (IoT) is an extensive system of interrelated devices equipped with sensors to monitor and track real world objects, spanning several verticals, covering many different industries. The IoT's promise is capturing interest as its value in healthcare continues to grow, as it can overlay on top of challenges dealing with the rising burden of chronic disease management and an aging population. To address difficulties associated with IoT-enabled healthcare, we propose a secure routing protocol that combines a fuzzy logic system and the Whale Optimization Algorithm (WOA) hierarchically. The suggested method consists of two primary approaches: the fuzzy trust strategy and the WOA-inspired clustering methodology. The first methodology plays a critical role in determining the trustworthiness of connected IoT equipment. Furthermore, a WOA-based clustering framework is implemented. A fitness function assesses the likelihood of IoT devices acting as cluster heads. This formula considers factors such as centrality, range of communication, hop count, remaining energy, and trustworthiness. Compared with other algorithms, the proposed method outperformed them in terms of network lifespan, energy usage, and packet delivery ratio by 47%, 58%, and 17.7%, respectively.

Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer.

BACKGROUND: The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear. AIM: To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer. METHODS: Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures. RESULTS: One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group (P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group (P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant (P < 0.05). And there were no statistical differences in complications between the two groups (P > 0.05). CONCLUSION: TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Regulation role of miR-204 on SIRT1/VEGF in metabolic memory induced by high glucose in human retinal pigment epithelial cells.

AIM: To examine the regulatory role of microRNA-204 (miR-204) on silent information regulator 1 (SIRT1) and vascular endothelial growth factor (VEGF) under high-glucose-induced metabolic memory in human retinal pigment epithelial (hRPE) cells. METHODS: Cells were cultured with either normal (5 mmol/L) or high D-glucose (25 mmol/L) concentrations for 8d to establish control and high-glucose groups, respectively. To induce metabolic memory, cells were cultured with 25 mmol/L D-glucose for 4d followed by culture with 5 mmol/L D-glucose for 4d. In addition, exposed in 25 mmol/L D-glucose for 4d and then transfected with 100 nmol/L miR-204 control, miR-204 inhibitor or miR-204 mimic in 5 mmol/L D-glucose for 4d. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to detect miR-204 mRNA levels. SIRT1 and VEGF protein levels were assessed by immunohistochemical and Western blot. Flow cytometry was used to investigate apoptosis rate. RESULTS: It was found that high glucose promoted miR-204 and VEGF expression, and inhibited SIRT1 activity, even after the return to normal glucose culture conditions. Upregulation of miR-204 promoted apoptosis inhibiting SIRT1 and increasing VEGF expression. However, downregulation of miR-204 produced the opposite effects. CONCLUSION: The study identifies that miR-204 is the upstream target of SIRT1 and VEGF, and that miR-204 can protect hRPE cells from the damage caused by metabolic memory through increasing SIRT1 and inhibiting VEGF expression.

Multidimensional engineering of Saccharomyces cerevisiae for the efficient production of heme by exploring the cytotoxicity and tolerance of heme.

Heme has attracted considerable attention due to its indispensable biological roles and applications in healthcare and artificial foods. The development and utilization of edible microorganisms instead of animals to produce heme is the most promising method to promote the large-scale industrial production and safe application of heme. However, the cytotoxicity of heme severely restricts its efficient synthesis by microorganisms, and the cytotoxic mechanism is not fully understood. In this study, the effect of heme toxicity on Saccharomyces cerevisiae was evaluated by enhancing its synthesis using metabolic engineering. The results showed that the accumulation of heme after the disruption of heme homeostasis caused serious impairments in cell growth and metabolism, as demonstrated by significantly poor growth, mitochondrial damage, cell deformations, and chapped cell surfaces, and these features which were further associated with substantially elevated reactive oxygen species (ROS) levels within the cell (mainly H2O2 and superoxide anion radicals). To improve cellular tolerance to heme, 5 rounds of laboratory evolution were performed, increasing heme production by 7.3-fold and 4.2-fold in terms of the titer (38.9 mg/L) and specific production capacity (1.4 mg/L/OD600), respectively. Based on comparative transcriptomic analyses, 32 genes were identified as candidates that can be modified to enhance heme production by more than 20% in S. cerevisiae. The combined overexpression of 5 genes (SPS22, REE1, PHO84, HEM4 and CLB2) was shown to be an optimal method to enhance heme production. Therefore, a strain with enhanced heme tolerance and ROS quenching ability (R5-M) was developed that could generate 380.5 mg/L heme with a productivity of 4.2 mg/L/h in fed-batch fermentation, with S. cerevisiae strains being the highest producers reported to date. These findings highlight the importance of improving heme tolerance for the microbial production of heme and provide a solution for efficient heme production by engineered yeasts.

CELA-MFP: a contrast-enhanced and label-adaptive framework for multi-functional therapeutic peptides prediction.

Functional peptides play crucial roles in various biological processes and hold significant potential in many fields such as drug discovery and biotechnology. Accurately predicting the functions of peptides is essential for understanding their diverse effects and designing peptide-based therapeutics. Here, we propose CELA-MFP, a deep learning framework that incorporates feature Contrastive Enhancement and Label Adaptation for predicting Multi-Functional therapeutic Peptides. CELA-MFP utilizes a protein language model (pLM) to extract features from peptide sequences, which are then fed into a Transformer decoder for function prediction, effectively modeling correlations between different functions. To enhance the representation of each peptide sequence, contrastive learning is employed during training. Experimental results demonstrate that CELA-MFP outperforms state-of-the-art methods on most evaluation metrics for two widely used datasets, MFBP and MFTP. The interpretability of CELA-MFP is demonstrated by visualizing attention patterns in pLM and Transformer decoder. Finally, a user-friendly online server for predicting multi-functional peptides is established as the implementation of the proposed CELA-MFP and can be freely accessed at http://dreamai.cmii.online/CELA-MFP.

Nicotinamide N-Methyltransferase (NNMT): A New Hope for Treating Aging and Age-Related Conditions.

The complex process of aging leads to a gradual deterioration in the function of cells, tissues, and the entire organism, thereby increasing the risk of disease and death. Nicotinamide N-methyltransferase (NNMT) has attracted attention as a potential target for combating aging and its related pathologies. Studies have shown that NNMT activity increases over time, which is closely associated with the onset and progression of age-related diseases. NNMT uses S-adenosylmethionine (SAM) as a methyl donor to facilitate the methylation of nicotinamide (NAM), converting NAM into S-adenosyl-L-homocysteine (SAH) and methylnicotinamide (MNA). This enzymatic action depletes NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and generates SAH, a precursor of homocysteine (Hcy). The reduction in the NAD+ levels and the increase in the Hcy levels are considered important factors in the aging process and age-related diseases. The efficacy of RNA interference (RNAi) therapies and small-molecule inhibitors targeting NNMT demonstrates the potential of NNMT as a therapeutic target. Despite these advances, the exact mechanisms by which NNMT influences aging and age-related diseases remain unclear, and there is a lack of clinical trials involving NNMT inhibitors and RNAi drugs. Therefore, more in-depth research is needed to elucidate the precise functions of NNMT in aging and promote the development of targeted pharmaceutical interventions. This paper aims to explore the specific role of NNMT in aging, and to evaluate its potential as a therapeutic target.

The association of maternal smoking around birth with chronic respiratory diseases in adult offspring: A Mendelian randomization study.

INTRODUCTION: Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS: Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS: After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (OR=1.001; 95% CI: 0.999-1.003; p=0.224), LC (OR=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS: In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged.

Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

Impact of butylparaben on growth dynamics and microcystin-LR production in Microcystis aeruginosa.

The presence of butylparaben (BP), a prevalent pharmaceutical and personal care product, in surface waters has raised concerns regarding its impact on aquatic ecosystems. Despite its frequent detection, the toxicity of BP to the cyanobacterium Microcystis aeruginosa remains poorly understood. This study investigates the influence of BP on the growth and physiological responses of M. aeruginosa. Results indicate that low concentrations of BP (below 2.5 mg/L) have negligible effects on M. aeruginosa growth, whereas higher concentrations (5 mg/L and 10 mg/L) lead to significant growth inhibition. This inhibition is attributed to the severe disruption of photosynthesis, evidenced by decreased Fv/Fm values and chlorophyll a content. BP exposure also triggers the production of reactive oxygen species (ROS), resulting in elevated activity of antioxidant enzymes. Excessive ROS generation stimulates the production of microcystin-LR (MC-LR). Furthermore, lipid peroxidation and cell membrane damage indicate that high BP concentrations cause cell membrane rupture, facilitating the release of MC-LR into the environment. Transcriptome analysis reveals that BP disrupts energy metabolic processes, particularly affecting genes associated with photosynthesis, carbon fixation, electron transport, glycolysis, and the tricarboxylic acid cycle. These findings underscore the profound physiological impact of BP on M. aeruginosa and highlight its role in stimulating the production and release of MC-LR, thereby amplifying environmental risks in aquatic systems.

Smooth Muscle Ythdf2 Abrogation Ameliorates Pulmonary Vascular Remodeling by Regulating Myadm Transcript Stability.

BACKGROUND: The N6-methyladenosine (m6A) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). Ythdf2 (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading m6A-modified mRNAs such as Hmox1 mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked Ythdf2 to the proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its specific roles in PASMCs and downstream targets during the development of PH remain unclear. METHODS: The expression and biological function of Ythdf2 in PASMCs were investigated in human and experimental models of PH. Smooth muscle cell-specific Ythdf2-deficient mice were used to assess the roles of Ythdf2 in PASMCs in vivo. Proteomic analysis, m6A sequencing, and RNA immunoprecipitation analysis were used to screen for potential downstream targets. RESULTS: Ythdf2 was significantly upregulated in human and rodent PH-PASMCs, and smooth muscle cell-specific Ythdf2 deficiency ameliorated PASMC proliferation, right ventricular hypertrophy, pulmonary vascular remodeling, and PH development. Higher expression of Ythdf2 promoted PASMC proliferation and PH by paradoxically stabilizing Myadm mRNA in an m6A-dependent manner. Loss of Ythdf2 decreased the expression of Myadm in PASMCs and pulmonary arteries, both in vitro and in vivo. Additionally, silencing Myadm inhibited the Ythdf2-dependent hyperproliferation of PASMCs by upregulating the cell cycle kinase inhibitor p21. CONCLUSIONS: We have identified a novel mechanism where the increased expression of Ythdf2 stimulates PH-PASMC proliferation through an m6A/Myadm/p21 pathway. Strategies targeting Ythdf2 in PASMCs might be useful additions to the therapeutic approach to PH.

The Impact of Silent Liver Disease on Hospital Length of Stay Following Isolated Coronary Artery Bypass Grafting Surgery.

Objectives: Risk assessment models for cardiac surgery do not distinguish between degrees of liver dysfunction. We have previously shown that preoperative liver stiffness is associated with hospital length of stay following cardiac surgery. The authors hypothesized that a liver stiffness measurement (LSM) ≥ 9.5 kPa would rule out a short hospital length of stay (LOS < 6 days) following isolated coronary artery bypass grafting (CABG) surgery. Methods: A prospective observational study of one hundred sixty-four adult patients undergoing non-emergent isolated CABG surgery at a single university hospital center. Preoperative liver stiffness measured by ultrasound elastography was obtained for each participant. Multivariate logistic regression models were used to assess the adjusted relationship between LSM and a short hospital stay. Results: We performed multivariate logistic regression models using short hospital LOS (<6 days) as the dependent variable. Independent variables included LSM (< 9.5 kPa, ≥ 9.5 kPa), age, sex, STS predicted morbidity and mortality, and baseline hemoglobin. After adjusting for included variables, LSM ≥ 9.5 kPa was associated with lower odds of early discharge as compared to LSM < 9.5 kPa (OR: 0.22, 95% CI: 0.06-0.84, p = 0.03). The ROC curve and resulting AUC of 0.76 (95% CI: 0.68-0.83) suggest the final multivariate model provides good discriminatory performance when predicting early discharge. Conclusions: A preoperative LSM ≥ 9.5 kPa ruled out a short length of stay in nearly 80% of patients when compared to patients with a LSM < 9.5 kPa. Preoperative liver stiffness may be a useful metric to incorporate into preoperative risk stratification.