FOXQ1, deubiquitinated by USP10, alleviates sepsis-induced acute kidney injury by targeting the CREB5/NF-κB signaling axis.

Sepsis-induced acute kidney injury (S-AKI) is a severe and frequent complication that occurs during sepsis. This study aimed to understand the role of FOXQ1 in S-AKI and its potential upstream and downstream regulatory mechanisms. A cecal ligation and puncture induced S-AKI mouse model in vivo and an LPS-induced HK-2 cell model in vitro were used. FOXQ1 was significantly upregulated in CLP mice and downregulated in the LPS-induced HK-2 cells. Upregulation of FOXQ1 improved kidney injury and dysfunction in CLP mice. Overexpression of FOXQ1 remarkably suppressed the apoptosis and inflammatory response via down-regulating oxidative stress indicators and pro-inflammatory factors (IL-1ß, IL-6, and TNF-α), both in vivo and in vitro. From online analysis, the CREB5/NF-κB axis was identified as the downstream target of FOXQ1. FOXQ1 transcriptionally activated CREB5, upregulating its expression. Overexpression of FOXQ1 suppressed the phosphorylation level and nucleus transport of p65. Rescue experiments showed that CREB5 mediates the protective role of FOXQ1 on S-AKI. Furthermore, FOXQ1 was identified as a substrate of USP10, a deubiquitinating enzyme. Ectopic expression of USP10 reduced the ubiquitination of FOXQ1, promoting its protein stability. USP10 upregulation alleviated LPS-induced cell apoptosis and inflammatory response, while suppression of FOXQ1 augmented these trends. Collectively, our results suggest that FOXQ1, deubiquitinated by USP10, plays a protective role in S-AKI induced inflammation and apoptosis by targeting CREB5/NF-κB axis.

Association of Maternal Fish Consumption and Omega-3 Supplement Use During Pregnancy With Child Autism-Related Outcomes: Results from a Cohort Consortium Analysis.

BACKGROUND: Prenatal fish intake is a key source of omega-3 polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: To examine associations of prenatal fish intake and omega-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and omega-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-Second Edition (n=3939 and n=3609 for fish intake analyses, respectively; n=4537 and n=3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (OR=0.84, 95% CI 0.77 to 0.92), and a modest reduction in raw total SRS scores (b=-1.69, 95% CI -3.3 to -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For omega-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (ß=1.98, 95% CI 0.33-3.64). CONCLUSIONS: These results extend prior work by suggesting that prenatal fish intake, but not omega-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low fish intake in the U.S. general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

Mediterranean diet improves blastocyst formation in women previously infected COVID-19: a prospective cohort study.

Objectives: Our study tries to investigate the effect of the Mediterranean diet (MeDiet) on assisted reproductive treatment outcomes in women after COVID-19 infection. Design: A prospective observational cohort study in the Reproductive and Genetic Hospital of CITIC-Xiangya from February 2023 to August 2023.Subjects: A total of 605 participants previously infected with COVID-19 were enrolled. Exposure: None. Main outcome measurement: The primary outcomes are oocyte and embryo quality. The secondary outcomes are pregnancy outcomes. Results: A majority of participants (n = 517) followed low to moderate MeDiet, and only a small group of them (n = 88) followed high MeDiet. The blastocyst formation rate is significantly higher in MeDiet scored 8-14 points women (46.08%), compared to the other two groups (which is 41.75% in the low adherence population and 40.07% in the moderate adherence population respectively) (p = 0.044). However, the follicle number on hCG day, yield oocytes, normal fertilized zygotes, fertilization rate, day three embryos (cleavage embryos), and embryo quality are comparable among the three groups. For those who received embryo transfer, we noticed an obvious trend that with the higher MeDiet score, the higher clinical pregnancy rate (62.37% vs. 76.09% vs. 81.25%, p = 0.197), implantation rate (55.84% vs. 66.44% vs. 69.23%, p = 0.240) and ongoing pregnancy rate (61.22% vs. 75.00% vs. 81.25%, p = 0.152) even though the p values are not significant. An enlarging sample size study, especially in a high adherence population should be designed to further verify the effects of MeDiet's role in improving IVF performance. Conclusion: High adherence to MeDiet is associated with improved blastocyst formation in women after COVID-19 infection. There is also a trend that high adherence to MeDiet might be beneficial to clinical pregnancy, embryo implantation as well as ongoing pregnancy in these women.

Metal-Coordinated NIR-II Nanoadjuvants with Nanobody Conjugation for Potentiating Immunotherapy by Tumor Metabolism Reprogramming.

Immune checkpoint blockade (ICB) immunotherapy remains hampered by insufficient immunogenicity and a high-lactate immunosuppressive tumor microenvironment (TME). Herein, a nanobody-engineered NIR-II nanoadjuvant with targeting metabolic reprogramming capability is constructed for potentiating NIR-II photothermal-ferroptosis immunotherapy. Specifically, the nanoadjuvant (2DG@FS-Nb) is prepared by metallic iron ion-mediated coordination self-assembly of D-A-D type NIR-II molecules and loading of glycolysis inhibitor, 2-deoxy-D-glucose (2DG), followed by modification with aPD-L1 nanobody (Nb), which can effectively target the immunosuppressive TME and trigger in situ immune checkpoint blockade. The nanoadjuvants responsively release therapeutic components in the acidic TME, enabling the precise tumor location by NIR-II fluorescence/photoacoustic imaging while initiating NIR-II photothermal-ferroptosis therapy. The remarkable NIR-II photothermal efficiency and elevated glutathione (GSH) depletion further sensitize ferroptosis to induce severe lipid peroxidation, provoking robust immunogenic cell death (ICD) to trigger anti-tumor immune response. Importantly, the released 2DG markedly inhibits lactate generation through glycolysis obstruction. Decreased lactate efflux remodels the immunosuppressive TME by suppressing M2 macrophage proliferation and downregulating regulatory T cell levels. This work provides a new paradigm for the integration of NIR-II phototheranostics and lactate metabolism regulation into a single nanoplatform for amplified anti-tumor immunotherapy combined with ICB therapy.

Receptor tyrosine kinase-like orphan receptor serves as a potential target in cancer immunotherapy.

Receptor tyrosine kinase-like orphan receptor (ROR), consisting of ROR1 and ROR2, is a conserved family of receptor tyrosine kinase superfamily that plays crucial roles during embryonic development with limited expression in adult normal tissues. However, it is overexpressed in a range of hematological malignancies and solid tumors and functions in cellular processes including cell survival, polarity, and migration, serving as a potential target in cancer immunotherapy. This review summarizes the expression and structure of ROR in developmental morphogenesis and its function in cancers associated with Wnt5a signaling and highlights the cancer immunotherapy strategies targeting ROR.

MBNL2 promotes aging-related cardiac fibrosis via inhibited SUMOylation of Krüppel-like factor4.

Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-ß1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-ß1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

Cu2(OH)3NO3/γ-Al2O3 catalyzes Fenton-like oxidation for the advanced treatment of effluent organic matter (EfOM) in fermentation pharmaceutical wastewater: The synergy of Cu2(OH)3NO3 and γ-Al2O3.

The secondary effluent of fermentation pharmaceutical wastewater exhibits high chromaticity, elevated salinity, and abundant refractory effluent organic matter (EfOM), presenting significant treatment challenges and environmental threats. Herein, Cu2(OH)3NO3/γ-Al2O3 was fabricated through ultrasound-assisted impregnation and calcination to catalyze the Fenton-like oxidation for degrading organic pollutants in this secondary effluent. Under neutral conditions, with 400.00 mg/L H2O2, 8 g/L catalyst, and at 30 ℃, the EfOM and CODCr removal efficiencies can reach 96.90 % and 51.56 %, respectively. The Cu2(OH)3NO3/γ-Al2O3 catalyst possesses ideal reusability, maintaining CODCr, chromaticity, and EfOM removal efficiencies at 44.44 %-64.59 %, 85.45 %-93.45 %, and 61.00 %-95.00 % over 220 h in a continuous-flow catalytic oxidation system operated at room temperatures (15-25 ℃). Electron paramagnetic resonance results and density functional theory calculations indicate that •OOH may be the predominant reactive oxygen species, facilitated by the easier elongation of the OH bond in H2O2 compared to the OO bond. The adjusted electronic structure endows Cu2(OH)3NO3/γ-Al2O3 composite sites with superior catalytic selectivity for H2O2 activation compared to Cu2(OH)3NO3 single crystal sites, with γ-Al2O3 additionally facilitating H2O2 activation through electron donation. This research highlights the efficacy of Cu2(OH)3NO3/γ-Al2O3 in the advanced treatment of complex industrial wastewater, elucidating its catalytic mechanisms and potential applications.

Take-out food enhances the risk of MPs ingestion and obesity, altering the gut microbiome in young adults.

Young people are consuming large amounts of microplastics (MPs) due to the booming development of the take-out industry. To investigate the association between MPs exposure and obesity, 121 volunteers were divided into high MPs exposure (HME) and low MPs exposure (LME) according to the frequency of take-out food consumption. Fecal samples were collected for MPs detection using Raman spectra analysis, and identification of the gut microbiota was based on 16 S rDNA/ITS, while metabolite analysis was performed by LC-MS/MS. High levels of MPs and body mass index (BMI) were observed in the HME group (P < 0.05). Both the multiple linear regression (MLR) model and the binary logistic regression (BLR) (OR: 1.264, 95 % CI: 1.108-1.441, P < 0.001) analysis showed a positive correlation between MPs content and BMI. Microbial community analysis revealed that Veillonella, Alistipes and Dothideomycotes (pathogenic fungi) increased in HME participants, whereas Faecalibacterium and Coprococcus decreased. Meanwhile, analysis of stool metabolites showed that vancomycin resistance, selenocompound metabolism and drug metabolism pathways were enhanced in HME participants. These findings indicate that frequent consumption of take-out food may elevate the intake of microplastics, consequently modifying the gut microbiota and metabolites of young adults, and could represent a potential risk factor for obesity.

The activation of adenosine monophosphate-activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin-1 via epithelial-mesenchymal transition.

BACKGROUND: The role of Claudin-1 in tongue squamous cell carcinoma (TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms. METHODS: 36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells. Claudin-1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMT-associated molecules was measured via western blotting. RESULTS: Claudin-1 expression decreased as TSCC malignancy increased. Adenosine monophosphate-activated protein kinase (AMPK) activation led to increased Claudin-1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial-mesenchymal transition (EMT). Conversely, Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation. CONCLUSIONS: Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.

Evaluation of Damage Stress Thresholds and Mechanical Properties of Granite: New Insights from Digital Image Correlation and GB-FDEM.

We employed a novel combination of digital image correlation (DIC) and grain-based hybrid finite-discrete element method (GB-FDEM) to improve the comprehension of the relationships between microstructural features and the mechanical properties of granitic rocks. DIC and numerical results showed that macrocracks initiated and propagated along grain boundaries among different minerals driven by the high stiffness contrast between the compliant biotite and the stiffer feldspar/quartz grains. Surface deformation analyses revealed that tensile-dominated macrocracks open at monotonically increased rates before the crack damage threshold, and the opening accelerated afterwards with the increased shear component. The onset of the acceleration of the opening rate of macrocracks can be used to infer the crack damage threshold. Both strain and acoustic emission were used to infer damage stress thresholds in the synthetic numerical samples. Numerical results showed that the damage stress thresholds and uniaxial compressive strength decrease with increasing grain size following log-linear relations. Coarse-grained samples tend to fail by axial splitting, while fine-grained samples fail by shear zone formation. Biotite and quartz contents significantly affect mechanical properties, while quartz to feldspar ratio is positively related to the mechanical properties. Our study demonstrates the capacities of DIC and GB-FDEM in inferring damage conditions in granitic rocks and clarifies the microstructural control of the macroscopic mechanical behaviors. Our results also provide a comprehensive understanding of the systematics of strain localization, crack development, and acoustic emission during the rock progressive failure process. Supplementary Information: The online version contains supplementary material available at 10.1007/s00603-024-03789-7.

Correlation of disulfidptosis and periodontitis: New insights and clinical significance.

OBJECTIVES: This study aims to investigate and predict the therapeutic agents associated with disulfidptosis in periodontitis. DESIGN: The dataset GSE10334 was downloaded from the Gene Expression Omnibus (GEO) database and used to train a least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithm to identify genes associated with disulfidptosis in periodontitis. GSE16134 validation sets, polymerase chain reaction (PCR), and gingival immunofluorescence were used to verify the results.Single-gene Gene Set Enrichment Analysis (GSEA) was performed to explore the potential mechanisms and functions of the characterized genes. Immune infiltration and correlation analyses were performed, and competing endogenous RNA (ceRNA) networks were constructed. Effective therapeutic drugs were then predicted using the DGIdb database, and molecular docking was used to validate binding affinity. RESULTS: Six genes (SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1) associated with disulfidptosis in periodontitis were obtained. Validation results from external datasets and experiments were consistent with the screening results. Single-gene GSEA analysis was mainly enriched for antigen presentation and immune-related pathways and functions.Immune infiltration and correlation analyses revealed significant regulatory relationships between these genes and plasma cells, resting dendritic cell, and activated NK cells. The ceRNA network was visualized. And ME-344, NV-128, and RILUZOLE, which have good affinity to target genes, were identified as promising agents for the treatment of periodontitis. CONCLUSIONS: SLC7A11, SLC3A2, RPN1, NCKAP1, LRPPRC, and NDUFS1 are targets associated with disulfidptosis in periodontitis, and ME-344, NV-128, and RILUZOLE are promising agents for the treatment of periodontitis.

Association of solid fuel use with cognitive function and the modifying role of lifestyle: A nationwide cohort study in China.

BACKGROUND: As opposed to a healthy lifestyle, indoor air pollution from solid fuel use may be harmful for cognitive function. However, the extent to which lifestyle modifies the association between solid fuel use and cognitive function remains unknown. METHODS: A total of 21,008 individuals aged 16 to 92 were enrolled in 2010 and followed up to 2014 in the China Family Panel Studies (CFPS). Cognitive function was assessed using standardized math and word tests in two waves. Solid fuel use at baseline was assessed by self-reporting of firewood, straw, or coal used for cooking. Lifestyle profile was classified into two groups (favorable vs. unfavorable) based on five modifiable lifestyle factors including alcohol drinking, smoking, body mass index, diet, and physical activity. Linear mixed-effects models were employed to assess the association of solid fuel use and lifestyle with cognitive function. The effect modification of lifestyle was analyzed. RESULTS: A total of 49.7% of the study population used solid fuels for cooking and 17.4% had a favorable lifestyle. Solid fuel use was associated with a significant decrease in cognitive function (ß = -0.29, 95% CI: -0.39, -0.19 for math test; ß = -0.62, 95% CI: -0.84, -0.41 for word test). Lifestyle significantly modified this association (p-interaction: 0.006 for math test; 0.016 for word test), with the corresponding association being less pronounced among participants adhering to a favorable lifestyle compared to those with an unfavorable lifestyle. CONCLUSION: A favorable lifestyle may attenuate the adverse association between solid fuel use and cognitive function. Adopting a favorable lifestyle has the potential to mitigate the adverse neurological effects due to indoor air pollution.

Effects of orthokeratology on corneal reshaping and the delaying of axial eye growth in children.

Purpose: To investigate the inhibition of myopia progression and axial elongation in children wearing orthokeratology (OK) lenses, as well as to evaluate the status of corneal reshaping, this study explores the relationship between changes in central corneal curvature (K-value) and e-value induced by OK lenses and axial elongation. Methods: In this study, it is planned to select children aged 8-15 who wear orthokeratology lenses at the Pediatric Ophthalmology and Strabismus Clinic of the Second Affiliated Hospital of Dalian Medical University. All children will undergo slit lamp examination, visual acuity assessment, computerized refraction, intraocular pressure measurement, biometry, and corneal topography examination before lens wear and at 1 month, 3 months, and 6 months after lens wear in the pediatric ophthalmology clinic. Based on age (lower age group (8 < age ≤12 years); higher age group (12 < age ≤15 years)) and baseline equivalent spherical (SE) value (mild myopia group (-1.00 D < SE ≤ -3.25D); moderate myopia group (-3.25 D < SE ≤ -6.00 D)), four groups will be formed by pairing these factors. Suitable data will be selected according to inclusion and exclusion criteria, and different groups will be included. Data will be organized, and statistical analysis will be performed using SPSS software to obtain the results. The expected results will be discussed and analyzed. Results: After wearing OK lenses, all four groups achieved good visual acuity at follow-up. At 6 months, there were no significant differences in visual acuity among the four groups (P = 0.149, >0.05). There were no significant differences in refractive error among the four groups (P = 0.066, >0.05). Baseline axial length differed significantly among the four groups (P = 0.000, <0.001), with the LM group having longer axial length than the LL group (P < 0.001, paired samples t-test), and the HM group having longer axial length than the HL group (P < 0.001, paired samples t-test). However, there were no significant differences in axial length change compared to baseline among the groups at 1 month, 3 months, and 6 months (P 1 = 0.053; P 3 = 0.557; P 6 = 0.329, >0.05). Significant differences were observed in corneal flat K-value change compared to baseline among the four groups at 1 month, 3 months, and 6 months (P 1 = 0.001, P 3 = 0.001, P 6 = 0.004, <0.05). There were no significant differences in e-value change among the groups at 1 and 3 months (P 1 = 0.205, P 3 = 0.252, >0.05), but significant differences were found in e-value change compared to baseline at 6 months (P 6 = 0.010, <0.05). Multiple regression analysis with changes in central corneal flat K-value and e-value as independent variables and axial elongation as the dependent variable showed a correlation between e-value change at 6 months and axial elongation (P = 0.004, <0.05), indicating a negative correlation. Conclusion: Orthokeratology (OK) lenses effectively improve myopic children's vision by reshaping the cornea, leading to reduced central corneal curvature and flattening of its anterior surface. The effectiveness of OK lenses is not significantly affected by age or initial myopia severity. Children of varying ages and myopia levels experience similar levels of axial length control with OK lens wear. Changes in corneal shape due to OK lenses affect axial elongation, with greater changes in corneal morphology associated with smaller increases in axial length.

M6A-modified lncRNA FAM83H-AS1 promotes colorectal cancer progression through PTBP1.

LncRNA plays a crucial role in cancer progression and targeting, but it has been difficult to identify the critical lncRNAs involved in colorectal cancer (CRC) progression. We identified FAM83H-AS1 as a tumor-promoting associated lncRNA using 21 pairs of stage IV CRC tissues and adjacent normal tissues. In vitro and in vivo experiments revealed that knockdown of FAM83H-AS1 in CRC cells inhibited tumor proliferation and metastasis, and vice versa. M6A modification is critical for FAM83H-AS1 RNA stability through the writer METTL3 and the readers IGF2BP2/IGFBP3. PTBP1-an RNA binding protein-is responsible for the FAM83H-AS1 function in CRC. T4 (1770-2440 nt) and T5 (2440-2743 nt) on exon 4 of FAM83H-AS1 provide a platform for PTBP1 RRM2 interactions. Our results demonstrated that m6A modification dysregulated the FAM83H-AS1 oncogenic role by phosphorylated PTBP1 on its RNA splicing effect. In patient-derived xenograft models, ASO-FAM83H-AS1 significantly suppressed the growth of gastrointestinal (GI) tumors, not only CRC but also GC and ESCC. The combination of ASO-FAM83H-AS1 and oxaliplatin/cisplatin significantly suppressed tumor growth compared with treatment with either agent alone. Notably, there was pathological complete response in all these three GI cancers. Our findings suggest that FAM83H-AS1 targeted therapy would benefit patients primarily receiving platinum-based therapy in GI cancers.

Serum C-reactive protein to albumin ratio as a potential risk indicator of pneumonia caused by Chlamydia psittaci: a multicenter retrospective study.

Introduction: The aim of the study was to describe psittacosis pneumonia and to assess the predictive value of the C-reactive protein/albumin ratio in psittacosis pneumonia for severity. Methods: Data on psittacosis pneumonia cases diagnosed using metagenomic sequencing were collected from three hospitals in Shanghai, China from Oct. 2019 to Oct. 2022. Serum levels of C-reactive protein and albumin were measured and the C-reactive protein to albumin ratio (CAR) was calculated. Spearman's correlation analysis, ordered logistic regression analysis, and receiver operating characteristic curve analysis were conducted to examine the correlation and predictive ability of the three indicators on the severity of the disease. Results: A total of 27 patients with psittacosis pneumonia were enrolled, with an average age of 62 years and 70.4% being male. 44.4% of patients had a clear history of contact with poultry or birds. The predominant symptom was fever (100%). Patients treated in the respiratory intensive care unit (RICU) had a higher likelihood of experiencing wheezing (88.9% versus 33.3%, P=0.013) and chest tightness (88.9% vs. 33.3%, P=0.013) than those in the general ward (Non-RICU). The proportion of patients with pleural effusion was significantly higher in the RICU compared to the Non-RICU (88.9% vs. 38.9%, P=0.019). The RICU group had a significantly higher CAR than the Non-RICU group (9.41 vs. 4.05, P=0.017). This result was accompanied by higher intubation and ventilator support (33.3% vs. 0.0%, P=0.029), higher PCT and CRP levels and lower albumin and PaCO2 levels in the RICU than in the Non-RICU. Logistic regression analysis indicated that CAR (OR 1.49; 95% CI 1.07-2.06, P=0.017) was risk factor for prolonged hospitalization (> 14 days). Discussion: Elevated serum CAR levels were found to be associated with a greater risk of severe psittacosis pneumonia. Consequently, it may serve as an uncomplicated and useful diagnostic tool for clinicians to promptly and precisely ascertain the severity of psittacosis pneumonia, ultimately aiding them in devising the most optimal therapeutic plan.

Genomic profiling of biosynthetic potentials of medicinal secondary metabolites for 'Aliisedimentitalea scapharcae' KCTC 42119T, isolated from ark shell.

Microorganisms living with higher organisms are valuable sources of bioactive substances like antibiotics, which could assist them competing for more and better nutrients or space. Here, we focused on a marine animal-associated bacterium, 'Aliisedimentitalea scapharcae' KCTC 42119T, which was isolated from ark shell collected from Gang-Jin bay of South Korea. We evaluated its biosynthetic potentials of medicinal secondary metabolites by de novo genome sequencing. The complete genome of strain KCTC 42119T sequenced is 5,083,900 bp and is comprised of one circular chromosome and four circular plasmids. Functional genome analysis by antiSMASH v7.1.0 showed that there are nine biosynthetic gene clusters encoded on the chromosome. The annotated secondary metabolites include antibiotic corynecin, cytoprotective ectoine and antineoplastic ET-743 (Yondelis), which suggested strain KCTC 42119T possesses potentials to synthesize a series of secondary metabolites of pharmaceutical utility. Genome analysis of 'A. scapharcae' also provides more insights into mining bioactive substances from animal-associated microorganisms.

Human brain proteome-wide association study provides insights into the genetic components of protein abundance in obesity.

BACKGROUNDS: Genome-wide association studies have identified multiple genetic variants associated with obesity. However, most obesity-associated loci were waiting to be translated into new biological insights. Given the critical role of brain in obesity development, we sought to explore whether obesity-associated genetic variants could be mapped to brain protein abundances. METHODS: We performed proteome-wide association studies (PWAS) and colocalization analyses to identify genes whose cis-regulated brain protein abundances were associated with obesity-related traits, including body fat percentage, trunk fat percentage, body mass index, visceral adipose tissue, waist circumference, and waist-to-hip ratio. We then assessed the druggability of the identified genes and conducted pathway enrichment analysis to explore their functional relevance. Finally, we evaluated the effects of the significant PWAS genes at the brain transcriptional level. RESULTS: By integrating human brain proteomes from discovery (ROSMAP, N = 376) and validation datasets (BANNER, N = 198) with genome-wide summary statistics of obesity-related phenotypes (N ranged from 325,153 to 806,834), we identified 51 genes whose cis-regulated brain protein abundance was associated with obesity. These 51 genes were enriched in 11 metabolic processes, e.g., small molecule metabolic process and metabolic pathways. Fourteen of the 51 genes had high drug repurposing value. Ten of the 51 genes were also associated with obesity at the transcriptome level, suggesting that genetic variants likely confer risk of obesity by regulating mRNA expression and protein abundance of these genes. CONCLUSIONS: Our study provides new insights into the genetic component of human brain protein abundance in obesity. The identified proteins represent promising therapeutic targets for future drug development.

Construction and evaluation of AuNPs enhanced electrochemical immunosensors with [Fe(CN)6]3-/4- and PPy probe for highly sensitive detection of human chorionic gonadotropin.

Human chorionic gonadotropin (HCG), a vital protein for pregnancy determination and a marker for trophoblastic diseases, finds application in monitoring early pregnancy and ectopic pregnancy. This study presents an innovative approach employing electrochemical immunosensors for enhanced HCG detection, utilizing Anti-HCG antibodies and gold nanoparticles (AuNPs) in the sensor platform. Two sensor configurations were optimized: BSA/Anti-HCG/c-AuNPs/MEL/e-AuNPs/SPCE with [Fe(CN)6]3-/4- as a redox probe (1) and BSA/Anti-HCG/PPy/e-AuNPs/SPCE using polypyrrole (PPy) as a redox probe (2). The first sensor offers linear correlation in the 0.10-500.00 pg∙mL-1 HCG range, with a limit of detection (LOD) of 0.06 pg∙mL-1, sensitivity of 32.25 µA∙pg-1∙mL∙cm-2, RSD <2.47 %, and a recovery rate of 101.03-104.81 %. The second sensor widens the HCG detection range (40.00 fg∙mL-1-5.00 pg∙mL-1) with a LOD of 16.53 fg∙mL-1, ensuring precision (RSD <1.04 %) and a recovery range of 94.61-106.07 % in serum samples. These electrochemical immunosensors have transformative potential in biomarker detection, offering enhanced sensitivity, selectivity, and stability for advanced healthcare diagnostics.

Structural characterization and adjuvant activity of a water soluble polysaccharide from Poria cocos.

Adjuvants, as the essential component of vaccines, are crucial in enhancing the magnitude, breadth and durability of immune responses. Unfortunately, commonly used Alum adjuvants predominantly provoke humoral immune response, but fail to evoke cellular immune response, which is crucial for the prevention of various chronic infectious diseases and cancers. Thus, it is necessary to develop effective adjuvants to simultaneously induce humoral and cellular immune response. In this work, we obtained a water soluble polysaccharide isolated and purified from Poria cocos, named as PCP, and explored the possibility of PCP as a vaccine adjuvant. The PCP, with Mw of 20.112 kDa, primarily consisted of →6)-α-D-Galp-(1→, with a small amount of →3)-ß-D-Glcp-(1 â†’ and →4)-ß-D-Glcp-(1→. Our results demonstrated that the PCP promoted the activation of dendritic cells (DCs) and macrophages in vitro. As the adjuvant to ovalbumin, the PCP facilitated the activation of DCs in lymph nodes, and evoked strong antibody response with a combination of Th1 and Th2 immune responses. Moreover, compared to Alum adjuvant, the PCP markedly induced a potent cellular response, especially the cytotoxic T lymphocytes response. Therefore, we confirmed that the PCP has great potential to be an available adjuvant for simultaneously inducing humoral and cellular immune responses.

Zinc Treatment of Tea Plants Improves the Synthesis of Trihydroxylated Catechins via Regulation of the Zinc-Sensitive Protein CsHIPP3.

The tea plant (Camellia sinensis [L.] O. Kussntze) is a global economic crop. Zinc treatment of tea plants can enhance catechin biosynthesis. However, the underlying molecular mechanism behind catechin formation through zinc regulation remains unclear. This study identified a zinc-responsive protein, C. sinensis heavy metal-associated isoprenylated plant protein 3 (CsHIPP3), from zinc-treated tea seedlings. CsHIPP3 expression was positively correlated with trihydroxylated catechin (TRIC) content. CsF3'5'H1 is a crucial regulator of the TRIC synthesis pathway. The interaction between CsHIPP3 and CsF3'5'H1 was assessed using bimolecular fluorescence complementation, firefly luciferase complementation imaging, and pulldown experiments. CsHIPP3 knockdown using virus-induced gene silencing technology decreased the content of each component of TRICs. Compared with the control, the relative catechin content was reduced by 40.12-55.39%. Co-overexpression of CsHIPP3 and CsF3'5'H1 significantly elevated the TRIC content in tea leaves and calli. Moreover, the TRIC content in transient co-overexpression leaves was 1.44-fold higher than that of the control group, and tea callus was 50.83% higher in transient co-overexpression than in the wild type. Thus, zinc-regulated TRIC synthesis in a zinc-rich environment was mediated by binding CsHIPP3 with CsF3'5'H1 to promote TRIC synthesis and accumulation.