Design and Synthesis of MarinePolybrominated Diphenyl Ether Derivatives as Potential Anti-inflammatory Agents.

Natural polybrominated diphenyl ethers are generally isolated from sponges and possess a broad range of biological activities. Through screening of our marine natural product library, we discovered that polybrominated diphenyl ethers 5 and 6 exhibit considerable anti-inflammatory activity. In order to expand our repertoire of derivatives for further biological activity studies, we designed and synthesized a series of 5-related polybrominated diphenyl ethers. Importantly, compound 5a showed comparable anti-inflammatory activity while much lower cytotoxicity on lipopolysaccharide (LPS)-induced RAW264.7 cells. Additionally, western blotting analysis showed that 5a reduced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK). Besides, molecular docking experiments were conducted to predict and elucidate the potential mechanisms underlying the varying anti-inflammatory activities exhibited by compounds 5a, 5, and 6.

CD200R promotes high glucose-induced oxidative stress and damage in human retinal pigment epithelial cells by activating the mTOR signaling pathway.

Diabetic retinopathy (DR) is established as the primary cause of visual impairment and preventable blindness, posing significant social and economic burdens on healthcare systems worldwide. Oxidative stress has been identified as a major contributor to DR, yet the precise role of the transmembrane glycoprotein CD200R in this context remains elusive. We studied human retinal pigment epithelia ARPE-19 cells to investigate the role of CD200R in high-glucose (HG) induced oxidative stress. Under HG conditions, we found a significant increase in CD200R expression in a time-dependent pattern. Conversely, knockdown of CD200R effectively alleviated oxidative stress and restored cell viability in HG-treated ARPE-19 cells, a phenomenon corroborated by the addition of a reactive oxygen species (ROS) scavenger. Exploration of the AKT/mTOR signaling pathway confirmed its mediating role regarding CD200R knockdown suppression of the expression of key proteins induced by HG conditions. Additionally, we found that the inhibition of mTOR signaling with Rapamycin effectively countered HG-induced oxidative stress in ARPE-19 cells, suggesting a promising therapeutic target against oxidative stress in the context of DR. This study establishes the crucial role of CD200R in HG-induced oxidative stress and identifies potential therapeutic avenues for the treatment of DR.

Minnelide exhibits antileukemic activity by targeting the Ars2/miR-190a-3p axis.

BACKGROUND: The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear. PURPOSE: To explore the molecular mechanisms by which minnelide exhibits antileukemic activity. METHODS: AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis. RESULTS: Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis. CONCLUSIONS: Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials.

Positively Charged Amino Acid-Modulated Interfacial Chemistry and Deposition Textures for Highly Reversible Zinc Anodes.

Interfacial active water molecule-induced parasitic reactions and stochastic Zn2+ transport-caused dendrite issue significantly impede the implementation of aqueous Zn-ion batteries. Herein, three positively charged amino acids, namely arginine, histidine, and lysine, were utilized as adsorption-type electrolyte additives to enhance the stability and reversibility of Zn anodes. Combined theoretical and experimental analyses verified that these amino acid cations can synergistically modulate the interfacial microenvironment and promote orientational Zn deposition. The adsorbed amino acid cations reconfigured the interfacial electric double layer structure, forming SO42-- and H2O-poor interfaces, thereby retarding hydrogen evolution and corrosion side reactions. Simultaneously, the preferential adsorption of the amino acid cations at specific facets induced crystallographic orientational Zn deposition along unterminated facets. Three deposition architectures, namely planar texture, subvertical alignment, and vertical erection, were obtained, all effectively inhibiting dendrite formation. Consequently, symmetric cells with the three amino acid cations exhibited high stripping/plating reversibility of over 2000 cycles at 5 mA cm-2. Moreover, MnO2-based full cells exhibited markedly improved stabilities compared with their additive-free counterparts.

Myopia prevalence and ocular biometry in children and adolescents at different altitudes: a cross-sectional study in Chongqing and Tibet, China.

OBJECTIVE: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China. DESIGN: Cross-sectional study. SETTING: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet. PARTICIPANTS: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study. METHODS: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)). RESULTS: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude. CONCLUSIONS: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening.

Functional Integration of Synthetic Cells into 3D Microfluidic Devices for Artificial Organ-on-Chip Technologies.

Microfluidics play a pivotal role in organ-on-chip technologies and in the study of synthetic cells, especially in the development and analysis of artificial cell models. However, approaches that use synthetic cells as integral functional components for microfluidic systems to shape the microenvironment of natural living cells cultured on-chip have not been explored. Here, we integrate colloidosome-based synthetic cells into 3D microfluidic devices, pioneering the concept of synthetic cell-based microenvironments for organs-on-chip. We devise methods to create dense and stable networks of silica colloidosomes, enveloped by supported lipid bilayers, within microfluidic channels. These networks promote receptor-ligand interactions with on-chip cultured cells. Furthermore, we introduce a technique for the controlled release of growth factors from the synthetic cells into the channels, using a calcium alginate-based hydrogel formation within the colloidosomes. To demonstrate the potential of the technology, we present a modular plug-and-play lymph-node-on-a-chip prototype that guides the expansion of primary human T cells by stimulating receptor ligands on the T cells and modulating their cytokine environment. This integration of synthetic cells into microfluidic systems offers a new direction for organ-on-chip technologies and suggests further avenues for exploration in potential therapeutic applications. This article is protected by copyright. All rights reserved.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

Macrophage-derived PDGF-BB modulates glycolytic enzymes expression and pyroptosis in nucleus pulposus cells via PDGFR-ß/TXNIP pathway.

OBJECTIVE: Intervertebral Disc Degeneration (IVDD) is one of the leading causes of low back pain, significantly impacting both individuals and society. This study aimed to investigate the significance of macrophage infiltration and the role of macrophage-secreted platelet-derived growth factor-BB (PDGF-BB) in IVDD progression. METHODS: To confirm the protective function of macrophage-derived PDGF-BB on nucleus pulposus cells (NPCs), we employed Lysm-Cre transgenic mice to genetically ablate PDGF-B within the myeloid cells. Immunohistochemistry was utilized to detect the expression of glycolytic enzymes and pyroptosis-related proteins during the process of IVDD. Western blot, RT-PCR, ELISA and immunofluorescence were used to detect the protective effect of recombinant PDGF-BB on NPCs. RESULTS: Macrophage-derived PDGF-BB deficiency resulted in the loss of NPCs and the increased ossification of cartilage endplates during lumbar disc degeneration. Also, PDGF-BB deficiency triggered the inhibition of glycolytic enzymes' expression and the activation of pathways related to pyroptosis in the nucleus pulposus. Mechanistically, our results suggest that PDGF-BB predominantly conveys its protective influence on NPCs through the PDGF receptor- beta (PDGFR-ß)/ thioredoxin-interacting protein pathway. CONCLUSIONS: The absence of PDGF-BB originating from macrophages expedites the advancement of IVDD, whereas the application of PDGF-BB treatment holds the potential for retarding intervertebral disc degeneration in the human body.

Effects of electroacupuncture on treatment-resistant chronic migraine with medication overuse headache: A 12-month follow-up case report.

Background: Medication overuse headache (MOH) is a secondary headache disorder that leads to pronounced disability and decreased quality of life. Available therapeutic options for MOH are limited, and many are only effective in a subset of individuals. Although the existing evidence is limited, acupuncture may be an effective treatment option for MOH. Case presentation: A 45-year-old Chinese woman presented to the Medical Acupuncture Department of Sanming Integrated Traditional Chinese and Western Medicine Hospital on April 11, 2022. Thirty-five years ago, she had episodic migraines. The frequency increased over time, however, and for the past 10 years she has had daily headaches. These headaches were characterized by daily persistent throbbing pain on the left side of the patient's head, accompanied by photophobia, phonophobia, neck stiffness, dizziness, and fatigue. Without painkillers, the patient rated her headache intensity as 9 out of 10 on a visual analog scale (0 = no pain, 10 = intolerable pain), and reported that the headaches lasted for up to 7 days or more. With painkillers, the headaches had a reduced intensity (5 of 10), but persisted. The patient had taken 1-3.5 compound aminopyrine phenacetin tablets daily for more than 5 years. Standard conservative therapy (patient education, medication withdrawal, and behavioral intervention) for MOH had failed to improve her symptoms. Before her visit, the patient had headache and engaged in short-term medication use on 30 days per month. The total monthly headache intensity score was 90. The patient's Migraine-Specific Quality of Life Questionnaire (MSQ) score was 33 points, her Hamilton Depression Scale (HAMD) score was 24 points, and her Hamilton Anxiety Scale (HAMA) score was 20 points. Results: After 48 acupuncture sessions over 24 weeks, the patient completely discontinued short-term analgesic use and the monthly number of headache days and headache intensity score were both reduced by 96.67 % (from 30 to 1 and 90 to 3, respectively), with no adverse effect. Compared with baseline, the MSQ, HAMD, and HAMA scores improved by 45, 17, and 16 points, respectively. At 12 months, the patient's condition remained stable and her MOH had not relapsed. Conclusion: In the context of the current literature and the present case, electroacupuncture shows promise for the long-term relief of chronic migraine with MOH when other treatments fail.

Sanghuangporus vaninii extract ameliorates hyperlipidemia in rats by mechanisms identified with transcriptome analysis.

The increasing incidence of hyperlipidemia is a serious threat to public health. The development of effective and safe lipid-lowering drugs with few side effects is necessary. The purpose of this study was to assess the lipid-lowering activity of Sanghuangporus vaninii extract (SVE) in rat experiments and reveal the molecular mechanism by transcriptome analysis. Hyperlipidemia was induced in the animals using a high-fat diet for 4 weeks. At the end of the 4th week, hyperlipidemic rats were assigned into two control groups (model and positive simvastatin control) and three treatment groups that received SVE at 200, 400, or 800 mg kg-1 day-1 for another 4 weeks. A last control group comprised normal chow-fed rats. At the end of the 8th week, rats were sacrificed and lipid serum levels, histopathology, and liver transcriptome profiles were determined. SVE was demonstrated to relieve the lipid disorder and improve histopathological liver changes in a dose-dependent manner. The transcriptomic analysis identified changes in hepatocyte gene activity for major pathways including steroid biosynthesis, bile secretion, cholesterol metabolism, AMPK signaling, thyroid hormone signaling, and glucagon signaling. The changed expression of crucial genes in the different groups was confirmed by qPCR. Collectively, this study revealed that SVE could relieve hyperlipidemia in rats, the molecular mechanism might be to promote the metabolism of lipids and the excretion of cholesterol, inhibit the biosynthesis of cholesterol by activating the AMPK signaling pathway, the thyroid hormone signaling pathway, and the glucagon signaling pathway.

Visual analysis of global research on the transient receptor potential ankyrin 1 channel: A literature review from 2002 to 2022.

Background and aims: The transient receptor potential ankyrin 1 (TRPA1) channel has become a focus in pain research. However, there are no bibliometric studies that systematically analyze the existing research in this area. This study aimed to provide a systematic review of the existing literature on TRPA1 using a bibliometric analysis. Methods: Published literature in the field of TRPA1 was collected from the Web of Science Core Collection database. Quantitative and qualitative analyses of publications, countries, institutions, authors, journals, and other entries were conducted using Excel, VOSview, and Citespace software to provide insight into global research hotspots and trends in the TRPA1 field. Results: This study included 1189 scientific products published in 398 journals from 52 countries. The United States of America (n = 367) had the most publications, ahead of Japan (n = 212) and China (n = 199). The University of Florence (n = 55) was the most productive institution and Pierangelo Geppetti (n = 46) was the most productive author. PLoS One (n = 40) published the most articles on TRPA1. Pain, cold, inflammation, covalent modification, hyperalgesia, and oxidative stress were the most common keywords used in the studies. Conclusion: This study provides the first bibliometric analysis of TRPA1 publications. The physiological functions of TRPA1, TRPA1, and neuropathic pain, TRPA1 as a therapeutic target, and agonists of TRPA1 are trending in TRPA1 research. Neuropathic pain, apoptosis, and sensitization could be focus areas of future research. This study provides important insight in the field of TRPA1 research.

Hotspots and trends of risk factors in gastric cancer: A visualization and bibliometric analysis.

BACKGROUND: The lack of specific symptoms of gastric cancer (GC) causes great challenges in its early diagnosis. Thus it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival rates. AIM: To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC, constructing a list of key risk factors, and providing a reference for early identification of patients at high risk for GC. METHODS: Research articles on risk factors for GC were searched in the Web of Science core collection, and relevant information was extracted after screening. The literature was analyzed using Microsoft Excel 2019, CiteSpace V, and VOSviewer 1.6.18. RESULTS: A total of 2514 papers from 72 countries and 2507 research institutions were retrieved. China (n = 1061), National Cancer Center (n = 138), and Shoichiro Tsugane (n = 36) were the most productive country, institution, or author, respectively. The research hotspots in the study of risk factors for GC are summarized in four areas, namely: Helicobacter pylori (H. pylori) infection, single nucleotide polymorphism, bio-diagnostic markers, and GC risk prediction models. CONCLUSION: In this study, we found that H. pylori infection is the most significant risk factor for GC; single-nucleotide polymorphism (SNP) is the most dominant genetic factor for GC; bio-diagnostic markers are the most promising diagnostic modality for GC. GC risk prediction models are the latest current research hotspot. We conclude that the most important risk factors for the development of GC are H. pylori infection, SNP, smoking, diet, and alcohol.

Application of Oral Retractor for Lip Injury Protection in Oral and Maxillofacial Surgeries: A Randomized Controlled Trial.

PURPOSE: Iatrogenic lip injury may occur during oral and maxillofacial surgical procedures. This study aimed to evaluate the effect of oral retractors on iatrogenic lip injury prevention during intraoral procedures of oral and maxillofacial surgery. METHODS: We conducted a randomized controlled trial and included patients who underwent intraoral procedures of oral and maxillofacial surgery. Patients were randomly allocated to receive oral retractor (intervention group) or traditional procedure without lip protection (control group). The incidence of lip injury was the outcome variable. Other study variables included surgical time and satisfaction of patients and surgeons with treatment experience evaluated by visual analog scale (VAS). Student t test and χ2 test were used to compare both groups' variables and measure the relationship between the predictor variable and the outcome variable. P<0.05 was considered significant for all analyses. RESULTS: A total of 114 patients were included, with 56 allocated to intervention group and 58 to control group. The results showed that the application of an oral retractor did not significantly increase surgical time (P=0.318). A total of 12 patients had lip injury, with 1 in the intervention group and 11 in the control group (P=0.003). For the assessment of satisfaction with treatment experience, the intervention group had significantly higher VAS scores for doctors and patients (P<0.05). CONCLUSIONS: We found that the oral retractor was a good tool for iatrogenic lip injury prevention in oral and maxillofacial surgical procedures and could be considered in clinical treatment.

Veno-arterial extracorporeal membrane oxygenation reduces myocardial and mitochondrial damage in acute myocardial infarction.

BACKGROUND: Myocardial infarction (MI) is a common cardiovascular disease with a high fatality rate once accompanied by cardiogenic shock. The efficacy of extracorporeal membrane oxygenation (ECMO) in treating myocardial infarction is controversial. METHODS: MI was induced by ligating the left anterior descending artery in adult male rats. Groups were defined as follows: MI group, reperfusion for 90 min after 30 min of left anterior descending artery (LAD) occlusion; MI + ECMO group, reperfusion and ECMO were performed for 90 min immediately after 30 min of LAD occlusion; prolonged MI + ECMO group, ECMO was used immediately after 30 minutes of occlusion with persistent occlusion of the LAD for an additional 30 minutes, followed by 90 minutes of reperfusion. The myocardial infarct size and mitochondrial morphology and function data were collected and compared of each group. RESULTS: The ECMO groups had a smaller myocardial infarct size and larger percentage ejection fraction. Compared with the prolonged MI + ECMO group, the immediate reperfusion group had a lower percentage of infarct size (63.28% versus 17.97% versus 31.22%, MI versus MI + ECMO versus prolonged MI + ECMO). Mitochondria isolated from the ischemic zone showed an intact mitochondrial structure, including fewer voids and broken crists, and preserved activity of mitochondrial complex II and complex IV in ECMO groups. CONCLUSIONS: ECMO support in myocardial infarction can reduce myocardial injury despite delayed coronary reperfusion.

Characterization and Function Analysis of miRNA Editing during Fat Deposition in Chinese Indigenous Ningxiang Pigs.

This study aimed to identify active miRNA editing sites during adipose development in Ningxiang pigs and analyze their characteristics and functions. Based on small RNA-seq data from the subcutaneous adipose tissues of Ningxiang pigs at four stages-30 days (piglet), 90 days (nursery), 150 days (early fattening), and 210 days (late fattening)-we constructed a developmental map of miRNA editing in the adipose tissues of Ningxiang pigs. A total of 505 miRNA editing sites were identified using the revised pipeline, with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G, and G-to-U. Importantly, these four types of miRNA editing exhibited base preferences. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. A total of nine miRNA editing sites were identified in the miRNA seed region, with significant differences in editing levels (p < 0.05) located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and KEGG enrichment analyses indicated that the editing of miR-497 might potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.

Role of ADAR1 on Proliferation and Differentiation in Porcine Preadipocytes.

Recent research has identified ADAR1 as a participant in the regulation of lipid accumulation in mice. However, there are no reports on the roles of ADAR1 in proliferation, apoptosis and differentiation of porcine preadipocytes. In this study, we investigated the role of ADAR1 in differentiation, proliferation and apoptosis of porcine preadipocytes using CCK-8, EdU staining, cell cycle detection, RT-qPCR, Western blot, a triglyceride assay and Oil Red O staining. The over-expression of ADAR1 significantly promoted proliferation but inhibited the differentiation and apoptosis of porcine preadipocytes. The inhibition of ADAR1 had the opposite effect on the proliferation, differentiation and apoptosis of porcine preadipocytes with over-expressed ADAR1. Then, the regulation mechanisms of ADAR1 on preadipocyte proliferation were identified using RNA-seq, and 197 DEGs in response to ADAR1 knockdown were identified. The MAPK signaling pathway is significantly enriched, indicating its importance in mediating fat accumulation regulated by ADAR1. The study's findings will aid in uncovering the mechanisms that regulate fat accumulation through ADAR1.

Using Machine Learning to Construct the Blood-Follicle Distribution Models of Various Trace Elements and Explore the Transport-Related Pathways with Multiomics Data.

Permeabilities of various trace elements (TEs) through the blood-follicle barrier (BFB) play an important role in oocyte development. However, it has not been comprehensively described as well as its involved biological pathways. Our study aimed to construct a blood-follicle distribution model of the concerned TEs and explore their related biological pathways. We finally included a total of 168 women from a cohort of in vitro fertilization-embryo transfer conducted in two reproductive centers in Beijing City and Shandong Province, China. The concentrations of 35 TEs in both serum and follicular fluid (FF) samples from the 168 women were measured, as well as the multiomics features of the metabolome, lipidome, and proteome in both plasma and FF samples. Multiomics features associated with the transfer efficiencies of TEs through the BFB were selected by using an elastic net model and further utilized for pathway analysis. Various machine learning (ML) models were built to predict the concentrations of TEs in FF. Overall, there are 21 TEs that exhibited three types of consistent BFB distribution characteristics between Beijing and Shandong centers. Among them, the concentrations of arsenic, manganese, nickel, tin, and bismuth in FF were higher than those in the serum with transfer efficiencies of 1.19-4.38, while a reverse trend was observed for the 15 TEs with transfer efficiencies of 0.076-0.905, e.g., mercury, germanium, selenium, antimony, and titanium. Lastly, cadmium was evenly distributed in the two compartments with transfer efficiencies of 0.998-1.056. Multiomics analysis showed that the enrichment of TEs was associated with the synthesis and action of steroid hormones and the glucose metabolism. Random forest model can provide the most accurate predictions of the concentrations of TEs in FF among the concerned ML models. In conclusion, the selective permeability through the BFB for various TEs may be significantly regulated by the steroid hormones and the glucose metabolism. Also, the concentrations of some TEs in FF can be well predicted by their serum levels with a random forest model.

A machine learning algorithm-based predictive model for pressure injury risk in emergency patients: A prospective cohort study.

OBJECTIVES: To construct pressure injury risk prediction models for emergency patients based on different machine learning algorithms, to optimize the best model, and to provide a suitable assessment tool for preventing the occurrence of pressure injuries in emergency patients. METHODS: A convenience sampling was used to select 312 patients admitted to the emergency department of a tertiary care hospital in Tianjin, China, from May 2022 to March 2023, and the patients were divided into a modeling group (n = 218) and a validation group (n = 94) in a 7:3 ratio. Based on the results of one-factor logistic regression analysis in the modeling group, three machine learning models, namely, logistic regression, decision tree, and neural network, were used to establish a prediction model for pressure injury in emergency patients and compare their prediction effects. The optimal model was selected for external validation of the model. RESULTS: The incidence of pressure injuries in emergency patients was 8.97 %, 64.52 % of pressure injuries occurred in the sacrococcygeal region, and 64.52 % were staged as stage 1. Serum albumin level, incontinence, perception, and mobility were independent risk factors for pressure injuries in emergency patients (P < 0.05), and the area under the ROC curve of the three models was 0.944-0.959, sensitivity was 91.8-95.5 %, specificity was 72.2-90.9 %, and the Yoden index was 0.677-0.802; the decision tree was the best model that The area under the ROC curve for the validation group was 0.866 (95 % CI: 0.688-1.000), with a sensitivity of 89.8 %, a specificity of 83.3 %, and a Yoden index of 0.731. CONCLUSIONS: The decision tree model has the best predictive efficacy and is suitable for individualized risk prediction of pressure injuries in emergency medicine specialties, which provides a reference for the prevention and early intervention of pressure injuries in emergency patients.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

Acute Ammonia Causes Pathogenic Dysbiosis of Shrimp Gut Biofilms.

Acute ammonia exposure has detrimental effects on shrimp, but the underlying mechanisms remain to be fully explored. In the present study, we investigated the impact of acute ammonia exposure on the gut microbiota of the white shrimp Litopenaeus vannamei and its association with shrimp mortality. Exposure to a lethal concentration of ammonia for 48 h resulted in increased mortality in L. vannamei, with severe damage to the hepatopancreas. Ammonia exposure led to a significant decrease in gut microbial diversity, along with the loss of beneficial bacterial taxa and the proliferation of pathogenic Vibrio strains. A phenotypic analysis revealed a transition from the dominance of aerobic to facultative anaerobic strains due to ammonia exposure. A functional analysis revealed that ammonia exposure led to an enrichment of genes related to biofilm formation, host colonization, and virulence pathogenicity. A species-level analysis and experiments suggest the key role of a Vibrio harveyi strain in causing shrimp disease and specificity under distinct environments. These findings provide new information on the mechanism of shrimp disease under environmental changes.