[Genetic analysis of a child with Dyschromatosis symmetrica hereditaria].

OBJECTIVE: To investigate the clinical and genetic features of a child with Dyschromatosis symmetrica hereditaria (DSH) and variant of the ADAR1 gene. METHODS: A child who was admitted to the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University in June 2020 due to irregular pigmented maculopapular rash on the dorsum of hands was selected as the study subject. Whole exome sequencing (WES) was carried out for the child and his similarly affected father, and Sanger sequencing was used to verify the candidate variant. SWISS-MODEL was used to predict the secondary and tertiary structures of the wild-type and mutant ADAR1 proteins. RESULTS: The child, a 13-year-old boy, had symmetrical hyperpigmented and depigmented spots on the back of his hands and was clinically diagnosed with DSH. WES and Sanger sequencing results showed that he and his father had both harbored a heterozygous c.2858dup (p.T954Dfs*20) truncating variant in exon 10 of the ADAR1 gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PM1+PP3). CONCLUSION: The c.2858dup (p.T954Dfs*20) variant of the ADAR1 gene probably underlay the DSH in this pedigree.

Correction: Study on the circadian rhythm and sleep state characteristics of patients with acute cerebral infarction accompanied by sleep-breathing disorders.

[This corrects the article DOI: 10.1007/s41105-024-00516-1.].

Segmentation of retinal microaneurysms in fluorescein fundus angiography images by a novel three-step model.

Introduction: Microaneurysms serve as early signs of diabetic retinopathy, and their accurate detection is critical for effective treatment. Due to their low contrast and similarity to retinal vessels, distinguishing microaneurysms from background noise and retinal vessels in fluorescein fundus angiography (FFA) images poses a significant challenge. Methods: We present a model for automatic detection of microaneurysms. FFA images were pre-processed using Top-hat transformation, Gray-stretching, and Gaussian filter techniques to eliminate noise. The candidate microaneurysms were coarsely segmented using an improved matched filter algorithm. Real microaneurysms were segmented by a morphological strategy. To evaluate the segmentation performance, our proposed model was compared against other models, including Otsu's method, Region Growing, Global Threshold, Matched Filter, Fuzzy c-means, and K-means, using both self-constructed and publicly available datasets. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union were calculated. Results: The proposed model outperforms other models in terms of accuracy, sensitivity, specificity, positive predictive value, and intersection-over-union. The segmentation results obtained with our model closely align with benchmark standard. Our model demonstrates significant advantages for microaneurysm segmentation in FFA images and holds promise for clinical application in the diagnosis of diabetic retinopathy. Conclusion: The proposed model offers a robust and accurate approach to microaneurysm detection, outperforming existing methods and demonstrating potential for clinical application in the effective treatment of diabetic retinopathy.

Study on the circadian rhythm and sleep state characteristics of patients with acute cerebral infarction accompanied by sleep-breathing disorders.

There is limited research on the circadian rhythm and sleep state in patients with acute cerebral infarction (ACI) accompanied by sleep-breathing disorders (SDB). This study aims to provide a scientific basis for individualized diagnosis and treatment for stroke-related SDB patients. The SC-500 sleep monitor was used to continuously monitor 1367 ACI patients over 5 days. Based on the apnea-hypopnea index (AHI), patients were divided into non-SDB group (normal) and SDB group (mild, moderate, severe, fluctuating). Interdaily stability (IS) and intradaily variability (IV) were calculated through heart rate monitoring, and sleep states and their correlations were analyzed. Compared to the non-SDB group, patients with moderate-to-severe ACI accompanied by SDB showed decreased IS, increased IV, and sleep fragmentation. Significant statistical differences were observed in total sleep time (TST), rapid eye movement latency (REML), sleep efficiency (SE), non-rapid eye movement stages 1-2 (NREM stages1-2), non-rapid eye movement stages 3-4 (NREM stages 3-4), proportion of non-rapid eye movement (NREM%), wake after sleep onset (WASO), and number of awakenings (NOA) between the SDB group and the non-SDB group (P < 0.05). AHI showed a strong negative correlation with IS and a strong positive correlation with IV. AHI was positively correlated with sleep latency (SL), REML, NREM stages1-2, NREM%, proportion of rapid eye movement (REM%), WASO, time out of bed (TOB), and NOA, and negatively correlated with TST, SE, NREM stages 3-4, and rapid eye movement (REM), all with statistical significance (P < 0.05). There were significant statistical differences in the Mini-Mental State Examination (MMSE) between patients with and without SDB, and among mild, moderate, severe, and fluctuating groups (P < 0.05). Patients with moderate-to-severe ACI accompanied by SDB are more likely to experience changes in circadian rhythm and sleep states, which in turn affect cognitive functions. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00516-1.

Cold tolerance SNPs and candidate gene mining in the soybean germination stage based on genome-wide association analysis.

KEY MESSAGE: Three QTLs associated with low-temperature tolerance were identified by genome-wide association analysis, and 15 candidate genes were identified by haplotype analysis and gene expression analyses. Low temperature is a critical factor affecting the geographical distribution, growth, development, and yield of soybeans, with cold stress during seed germination leading to substantial productivity loss. In this study, an association panel comprising 260 soybean accessions was evaluated for four germination traits and four cold tolerance index traits, revealing extensive variation in cold tolerance. Genome-wide association study (GWAS) identified 10 quantitative trait nucleotides (QTNs) associated with cold tolerance, utilizing 30,799 single nucleotide polymorphisms (SNPs) and four GWAS models. Linkage disequilibrium (LD) analysis positioned these QTNs within three cold-tolerance quantitative trait loci (QTL) and, with QTL19-1, was positioned by three multi-locus models, underscoring its importance as a key QTL. Integrative haplotype analysis, supplemented by transcriptome analysis, uncovered 15 candidate genes. The haplotypes within the genes Glyma.18G044200, Glyma.18G044300, Glyma.18G044900, Glyma.18G045100, Glyma.19G222500, and Glyma.19G222600 exhibited significant phenotypic variations, with differential expression in materials with varying cold tolerance. The QTNs and candidate genes identified in this study offer substantial potential for marker-assisted selection and gene editing in breeding cold-tolerant soybeans, providing valuable insights into the genetic mechanisms underlying cold tolerance during soybean germination.

Sustained release of brimonidine from conjunctival sac insert to reduce intraocular pressure for glaucoma treatment.

BACKGROUND: Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance. METHODS: A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed. RESULTS: The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion. CONCLUSIONS: The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without need for invasive procedures.

Experimental study on the mechanical properties of desert sand improved by the combination of additives and bio-cement.

Bio-cement is a green and energy-saving building material that has attracted much attention in the field of ecological environment and geotechnical engineering in recent years. The aim of this study is to investigate the use of bio-cement (enzyme-induced calcium carbonate precipitation-EICP) in combination with admixtures for the improvement of desert sands, which can effectively improve the mechanical properties of desert sands and is particularly suitable for sand-rich countries. In addition, the suitability of tap water in bio-cement was elucidated and the optimum ratio of each influencing factor when tap water is used as a solvent was derived. The results showed that peak values of unconfined compressive strength (maximum increase of about 130 times), shear strength (increase of 27.09%), calcium carbonate precipitation value (increase of about 4.39 times), and permeability (decrease of about 93.72 times) were obtained in the specimens modified by EICP combined with admixture as compared to the specimens modified by EICP only. The incorporation of skimmed milk powder, though significantly increasing the strength, is not conducive to cost control. The microscopic tests show that the incorporation of admixtures can provide nucleation sites for EICP, thus improving the properties of desert sand. This work can provide new research ideas for cross-fertilization between the disciplines of bio-engineering, ecology, and civil engineering.

Transcriptome-metabolome reveals the molecular changes in meat production and quality in the hybrid populations of Sichuan white goose.

Hybrid breeding has proven to enhance meat quality and is extensively utilized in goose breeding. Nevertheless, there is a paucity of research investigating the molecular mechanisms that underlie the meat quality of hybrid geese. In this study, we employed the Sichuan White Goose as the maternal line for hybridization with the Zhedong White Goose and Tianfu Meat Goose P3 line. We assessed the growth and slaughter meat quality performance of 10-wk-old hybrid offspring in comparison to Sichuan white goose purebred offspring. The results indicate that hybrid geese have significantly improved performance in growth and slaughter meat quality. Furthermore, we conducted a comprehensive analysis of the chest muscles of hybrid offspring through transcriptomics and metabolomics to unravel the effects of hybrid breeding on growth and meat quality. A total of 673 differentially expressed genes (DEGs), and 93 differentially expressed metabolites were identified. The joint analysis highlighted the significant enrichment of DEGs AMPD1, AMPD3, RRM2, ENTPD3, and the metabolite UMP in the nucleotide metabolism pathway. These findings underscore the crucial role of these genetic and metabolic factors in regulating muscle growth and meat quality in hybrid populations.

Comparative efficacy of immune checkpoint inhibitors versus chemotherapy alone in diffuse pleural mesothelioma.

BACKGROUND: This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real-world diffuse pleural mesothelioma patients in China. METHODS: Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs-treated group (n = 46) and the chemotherapy-only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. RESULTS: The median progression-free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs-treated group and the chemotherapy group, respectively. The ICIs-treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan-Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38-0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26-0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. CONCLUSION: In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first- and second-/third-line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

Portable all-in-one microfluidic system for CRISPR-Cas13a-based fully integrated multiplexed nucleic acid detection.

Point-of-care testing of "sample in, answer out" is urgently needed for communicable diseases. Recently, rapid nucleic acid tests for infectious diseases have been developed for use in resource-limited areas, but they require types of equipment in central laboratories and are poorly integrated. In this work, a portable centrifugal microfluidic testing system is developed, integrated with magnetic bead-based nucleic acid extraction, recombinase-assisted amplification and CRISPR-Cas13a detection. The system, with the advantage of its power-supplied active rotating chip and highly programable flow control through integrated addressable active thermally-triggered wax valves, has a rapid turnaround time within 45 min, requiring only one user step. All reagents are preloaded into the chip and can be automatically released. By exploiting a multichannel chip, it is capable of simultaneously detecting 10 infectious viruses with limits of detection of 1 copy per reaction and 5 copies per reaction in plasmid samples and mock plasma samples, respectively. The system was used to analyse clinical plasma samples with good consistency compared to laboratory-based molecular testing. Moreover, the generalizability of our device is reported by successfully testing nasopharyngeal swabs and whole blood samples. The portable device does not require the operation of professional technicians, making it an excellent assay for on-site testing.

Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients.

Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

Astragalus Polysaccharide Modulates the Gut Microbiota and Metabolites of Patients with Type 2 Diabetes in an In Vitro Fermentation Model.

This study investigated the effect of astragalus polysaccharide (APS, an ingredient with hypoglycemic function in a traditional Chinese herbal medicine) on gut microbiota and metabolites of type 2 diabetes mellitus (T2DM) patients using a simulated fermentation model in vitro. The main components of APS were isolated, purified, and structure characterized. APS fermentation was found to increase the abundance of Lactobacillus and Bifidobacterium and decrease the Escherichia-Shigella level in the fecal microbiota of T2DM patients. Apart from increasing propionic acid, APS also caused an increase in all-trans-retinoic acid and thiamine (both have antioxidant properties), with their enrichment in the KEGG pathway associated with thiamine metabolism, etc. Notably, APS could also enhance fecal antioxidant properties. Correlation analysis confirmed a significant positive correlation of Lactobacillus with thiamine and DPPH-clearance rate, suggesting the antioxidant activity of APS was related to its ability to enrich some specific bacteria and upregulate their metabolites.

Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats.

Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea's collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.

Omadacycline for the treatment of patients with Legionella pneumophila pneumonia after experiencing liver dysfunction: case series.

Introduction: Antibiotics frequently induce abnormal liver function. Omadacycline is a novel aminomethylcycline antibiotic, which shows potent activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical (including Legionella pneumophila) bacteria. Of note, omadacycline is tolerable in most patients with liver impairment. However, evidence regarding the application of omadacycline in patients with Legionella pneumophila pneumonia after experiencing liver dysfunction is scarce. Methods: The current study reported 6 cases of patients with Legionella pneumophila pneumonia receiving omadacycline as subsequent antibiotics after experiencing liver dysfunction. Results: These 6 cases were admitted to the hospital for pneumonia and received antibiotic therapy, including piperacillin-tazobactam, imipenem, meropenem, and moxifloxacin. After receiving these antibiotics, increased liver enzymes were noted. Although hepatoprotective therapy (such as magnesium isoglycyrrhizinate and glutathione) was given, the liver function was still abnormal. According to metagenomic next-generation sequencing, these patients were diagnosed with Legionella pneumophila pneumonia. Considering the abnormal liver function, the antibiotic therapy was switched to omadacycline-containing antibiotic therapy. After that, liver function was improved, and the infection was ameliorated. Ultimately, all patients discharged from the hospital, including 2 patients who achieved complete clinical symptomatic improvement and 4 patients who achieved partial clinical symptomatic improvement. Discussion: This study emphasizes the successful treatment of switching to omadacycline after experiencing abnormal liver function in patients with Legionella pneumophila pneumonia. This study suggests that omadacycline may serve as an optional antibiotic for patients with Legionella pneumophila pneumonia, especially when occurring liver dysfunction. However, more clinical studies are required to validate our findings.

A severe case of iatrogenic botulism associated with COVID-19 infection.

Background: The botulinum toxin is an extremely potent substance that impacts the nervous system. There has been a rise in cases of medical poisoning associated with it, particularly in the field of plastic and aesthetic procedures, in recent years. Case description: A 51-year-old woman underwent a facial wrinkle reduction procedure with an unauthorized injection of 100 U of botulinum toxin at an unlicensed medical facility six days prior to hospitalization. Over time, her toxicity symptoms intensified, impacting her respiratory muscles, and she did not receive antitoxin treatment. She was concurrently diagnosed with a COVID-19 infection during this period. Nonetheless, she experienced a full recovery 86 days after the injection. Conclusion: Currently, there is no effective antidote for botulism. Nevertheless, the timely administration of antitoxin can contribute to reducing the duration of the illness, alleviating symptoms, and preventing its recurrence. It is essential to recognize that individual responses may vary, and in this instance, the absence of antitoxin treatment did not significantly prolong the course of the disease. Accurate diagnosis of medical poisoning can be based on injection history and clinical symptoms. Early indications like fatigue and dry mouth warrant particular attention, emphasizing the importance of immediate medical intervention. To address emergencies, the Center for Disease Control (CDC) should maintain an accessible supply of antitoxin. Patients with severe poisoning should be hospitalized until their respiratory muscle strength is fully restored.

Effects of a manganese complex with lysine and glutamic acid on growth performance, manganese deposition, and emission, antioxidant capacity and metacarpal strength in weaned piglets.

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ±â€…0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.

This research explored the effects of a manganese complex containing lysine and glutamic acid (Mn-LG) on various health parameters in weaned piglets. Utilizing samples of 288 piglets, the study investigated how Mn-LG supplementation influences growth performance, Mn deposition and emission, antioxidant capacity, and metacarpal strength. Key findings include an increase in serum Mn levels and Mn superoxide dismutase (Mn-SOD) activity, a reduction in diarrhea incidence, and no significant effects in bone strength indices in piglets receiving Mn-LG. Additionally, the fecal Mn concentration was notably lower in the Mn-LG group than in the group receiving inorganic Mn at equivalent dosages.

Ganoderma lucidum spores-derived particulate ß-glucan treatment improves antitumor response by regulating myeloid-derived suppressor cells in triple-negative breast cancer.

Granular ß-1,3-glucan extracted from the wall of Ganoderma lucidum spores, named GPG, is a bioregulator. In this study, we investigated the structural, thermal, and other physical properties of GPG. We determined whether GPG ameliorated immunosuppression caused by Gemcitabine (GEM) chemotherapy. Triple-negative breast cancer mice with GPG combined with GEM treatment had reduced tumor burdens. In addition, GEM treatment alone altered the tumor microenvironment(TME), including a reduction in antitumor T cells and a rise in myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs). However, combined GPG treatment reversed the tumor immunosuppressive microenvironment induced by GEM. GPG inhibited bone marrow (BM)-derived MDSC differentiation and reversed MDSC expansion induced by conditioned medium (CM) in GEM-treated E0771 cells through a Dectin-1 pathway. In addition, GPG downgraded PD-L1 and IDO1 expression on MDSC while boosting MHC-II, CD86, TNF-α, and IL-6 expression. In conclusion, this study demonstrated that GPG could alleviate the adverse effects induced by GEM chemotherapy by regulating TME.

Adenosine kinase inhibition protects mice from abdominal aortic aneurysm via epigenetic modulation of VSMC inflammation.

AIM: Abdominal aortic aneurysm (AAA) is a common, serious vascular disease with no effective pharmacological treatment. The nucleoside adenosine plays an important role in modulating vascular homeostasis, which prompted us to determine whether adenosine kinase (ADK), an adenosine metabolizing enzyme, modulates AAA formation via control of intracellular adenosine level, and to investigate the underlying mechanisms. METHODS AND RESULTS: We used a combination of genetic and pharmacological approaches in murine models of AAA induced by calcium chloride (CaCl2) application or angiotensin II (Ang II) infusion to study the role of ADK in the development of AAA. In vitro functional assays were performed by knocking down ADK with adenovirus-short hairpin RNA in human vascular smooth muscle cells (VSMCs), and the molecular mechanisms underlying ADK function were investigated using RNA-sequencing, isotope tracing and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). Heterozygous deficiency of Adk protected mice from CaCl2- and Ang II-induced AAA formation. Moreover, specific knockout of Adk in VSMCs prevented Ang II-induced AAA formation, as evidenced by reduced aortic extracellular elastin fragmentation, neovascularization and aortic inflammation. Mechanistically, ADK knockdown in VSMCs markedly suppressed the expression of inflammatory genes associated with AAA formation, and these effects were independent of adenosine receptors. Metabolic flux and ChIP-qPCR results showed that ADK knockdown in VSMCs decreased S-adenosylmethionine (SAM)-dependent transmethylation, thereby reducing H3K4me3 binding to the promoter regions of the genes that are associated with inflammation, angiogenesis and extracellular elastin fragmentation. Furthermore, the ADK inhibitor ABT702 protected mice from CaCl2-induced aortic inflammation, extracellular elastin fragmentation and AAA formation. CONCLUSION: Our findings reveal a novel role for ADK inhibition in attenuating AAA via epigenetic modulation of key inflammatory genes linked to AAA pathogenesis.