A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury.

JOURNAL/nrgr/04.03/01300535-202502000-00028/figure1/v/2024-05-28T214302Z/r/image-tiff Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases. However, conventional topical drug delivery often results in a burst release of the drug, leading to transient retention (inefficacy) and undesirable diffusion (toxicity) in vivo. Therefore, a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke. Matrix metalloproteinase-2 (MMP-2) is gradually upregulated after cerebral ischemia. Herein, vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG (TIMP) and customizable peptide amphiphilic (PA) molecules to construct nanofiber hydrogel PA-TIMP-QK. PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro. The results indicated that PA-TIMP-QK promoted neuronal survival, restored local blood circulation, reduced blood-brain barrier permeability, and restored motor function. These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Nanoenzyme Hydrogel Film-Based Portable Point-of-Care Testing Platform for Double-Signal Visual Detection of PSA.

The development of the Point-of-Care Testing (POCT) platform that combines convenience and cost-effectiveness is crucial for enabling the visual detection of disease biomarkers. In this work, a POCT platform for the sensitive in situ detection of prostate specific antigen (PSA) with dual-signal output was constructed by functionalizing the Eppendorf (EP) tube. This was achieved through the modification of aptamer hairpin probes (AHPs) on the lid of the EP tube and the assembly of a nanoenzyme hydrogel film on its inner wall. The target could trigger the release of Ag+ by AHP and subsequently activate Ag+-dependent DNAzyme (Ag-DNAzyme). This would initiate the cleavage of the DNA-Au/Pt NP hydrogel network, leading to the release of Au/Pt NPs. The released Au/Pt NPs exhibit both peroxidase (POD)-like and catalase (CAT)-like activity to produce a colorimetric response and induce liquid flow under pressure. Therefore, the target can be measured visually and quantitatively through colorimetric analysis and the measurement of total dissolved solids (TDS) using a pressure-triggered liquid flow device integrated into the platform. The designed platform is distinguished by its simplicity, specificity, cost-effectiveness, and remarkable sensitivity. It allows for the visual detection of PSA within concentration ranges of 0.5-100 ng/L (colorimetric) and 3-100 ng/L (TDS reading), boasting detection limits as low as 0.15 ng/L (colorimetric) and 0.57 ng/L (TDS reading). The strategy of target-triggered nanoenzyme release significantly enhances sensitivity and provides a guiding approach for visual biomarker detection.

miR-100 and miR-125b Contribute to Enhanced 3D Growth and Invasiveness and can be Functionally Transferred to Silence Target Genes in Recipient Cells.

Extracellular communication via the transfer of vesicles and nanoparticles is now recognized to play an important role in tumor microenvironment interactions. Cancer cells upregulate and secrete abundant levels of miR-100 and miR-125b that can alter gene expression by both cell- and non-cell-autonomous mechanisms. We previously showed that these miRNAs activate Wnt signaling in colorectal cancer (CRC) through noncanonical pairing with 5 negative regulators of Wnt signaling. To identify additional targets of miR-100 and miR-125b , we used bioinformatic approaches comparing multiple CRC cell lines, including knockout lines lacking one or both of these miRNAs. From an initial list of 96 potential mRNA targets, we tested 15 targets with 8 showing significant downregulation in the presence of miR-100 and miR-125b . Among these, Cingulin (CGN) and Protein tyrosine phosphatase receptor type-R (PTPRR) are downregulated in multiple cancers, consistent with regulation by increased levels of miR-100 and miR-125b. We also show that increased cellular levels of miR-100 and miR-125b enhance 3D growth and invasiveness in CRC and glioblastoma cell lines. Lastly, we demonstrate that extracellular transfer of miR-100 and miR-125b can silence both reporter and endogenous mRNA targets in recipient cells and also increase the invasiveness of recipient spheroid colonies when grown under 3D conditions in type I collagen.

Point mutations in the voltage-gated sodium channel gene conferring pyrethroid resistance in China populations of the Dermanyssus gallinae.

BACKGROUND: Dermanyssus gallinae, the poultry red mite (PRM), is a worldwide ectoparasite posing significant economic challenges in poultry farming. The extensive use of pyrethroids for PRM control has led to the emergence of pyrethroid resistance. The objective of this study is to detect the pyrethroid resistance and explore its associated point mutations in the voltage-gated sodium channel (VGSC) gene among PRM populations in China. RESULTS: Several populations of D. gallinae, namely CJF-1, CJP-2, CJP-3, CSD-4 and CLD-5, displayed varying degrees of resistance to beta-cypermethrin compared to a susceptible field population (CBP-5). Mutations of VGSC gene in populations of PRMs associated with pyrethroid resistance were identified through sequencing its fragments IIS4-IIS5 and IIIS6. The mutations I917V, M918T/L, A924G and L925V were present in multiple populations, while no mutations were found at positions T929, I936, F1534 and F1538. CONCLUSION: The present study confirmed the presence of extremely high levels of pyrethroid resistance in PRM populations in China, and for the first time detected four pyrethroid resistance mutations in the VGSC gene. Identifying pyrethroid resistance in the field population of PRM in China can be achieved through screening for VGSC gene mutations as an early detection method. Our findings underscore the importance of implementing chemical PRM control strategies based on resistance evidence, while also considering the management of acaricide resistance in the control of PRMs. © 2024 Society of Chemical Industry.

Sodium alginate/gelatin hydrogel spheres loaded with Fructus Ligustri Lucidi essential oil: Preparation, characterization and biological activity.

The application of plant essential oils in the food industry is often hindered by their poor water solubility and high volatilize. Encapsulation has emerged as an effective solution to this problem. This study focuses on the preparation of Fructus Ligustri Lucidi essential oil gel spheres (FEOH) based sodium alginate and gelatin. The optimum formulation for FEOH was established by Box-Behnken Design response surface testing, resulting in a composition of 10 % FEO, 5 % TW20 and 2 % CaCl2. This formulation achieved an encapsulation efficiency of 85.56 %. FTIR and SEM results indicated the successful encapsulation of FEO within the gel spheres. Furthermore, DSC and TGA results showed that encapsulation enhanced the thermal stability of the essential oil. At room temperature, the water content of FEOH exceeded 90 %, and it showed the highest swelling ratio of 62.5 % in an alkaline medium at different pH conditions. The in vitro release behavior showed that FEOH was released up to 85.28 % in oil-based food simulants within 2 h. FEOH showed strong antibacterial activity, with a Minimum Inhibitory Concentration (MIC) of 128 mg/mL against Staphylococcus aureus and 256 mg/mL against Escherichia coli. The gel spheres obtained in this research show significant potential as food preservatives in food matrices.

Rainfall seasonality shapes microbial assembly and niche characteristics in Yunnan Plateau lakes, China.

Microorganisms are crucial components of freshwater ecosystems. Understanding the microbial community assembly processes and niche characteristics in freshwater ecosystems, which are poorly understood, is crucial for evaluating microbial ecological roles. The Yunnan Plateau lakes in China represent a freshwater ecosystem that is experiencing eutrophication due to anthropogenic activities. Here, variation in the assembly and niche characteristics of both prokaryotic and microeukaryotic communities was explored in Yunnan Plateau lakes across two seasons (dry season and rainy season) to determine the impacts of rainfall and environmental conditions on the microbial community and niche. The results showed that the environmental heterogeneity of the lakes decreased in the rainy season compared to the dry season. The microbial (bacterial and microeukaryotic) α-diversity significantly decreased during the rainy season. Deterministic processes were found to dominate microbial community assembly in both seasons. ß-diversity decomposition analysis revealed that microbial community compositional dissimilarities were dominated by species replacement processes. The co-occurrence networks indicated reduced species complexity for microbes and a destabilized network for prokaryotes prior to rainfall, while the opposite was found for microeukaryotes following rainfall. Microbial niche breadth decreased significantly in the rainy season. In addition, lower prokaryotic niche overlap, but greater microeukaryotic niche overlap, was observed after rainfall. Rainfall and environmental conditions significantly affected the microbial community assembly and niche characteristics. It can be concluded that rainfall and external pollutant input during the seasonal transition alter the lake environment, thereby regulating the microbial community and niche in these lakes. Our findings offer new insight into microbiota assembly and niche patterns in plateau lakes, further deepening the understanding of freshwater ecosystem functioning.

Spatiotemporal dynamic of rice production and its carbon footprint in Hainan, China: Implications for food security and environmental sustainability.

Rice (Oryza sativa L.) feeds more than half of the global population and faces the critical issues related to food security and environmental sustainability. This study analyzed double rice production data from 2010 to 2020 to assess its spatiotemporal dynamic in food production and carbon (C) footprint in Hainan province, China. The results revealed a 29.5% reduction in rice planting area, leading to a significantly decreased rice self-sufficiency rate from 38% to 33% from 2010 to 2020. During this period, the carbon footprint per unit area (CFa) for early, late, and double rice showed a fluctuating upward trend ranging from 8.1 to 8.4, 8.9 to 9.2, and 17.0 to 17.4 t CO2-eq ha-1, respectively. The total greenhouse gas (GHG) emissions of rice production decreased to around 2 million t CO2-eq, primarily due to reduced planting area. The C sequestration initially increased before decreasing to 1.2 million t C in 2020 at a temporal scale. Spatially, the northeast and southwest regions exhibited ∼70% of the total GHG emissions and ∼80% of C sequestration. The regional C footprint per unit yield displayed less favorable outcomes, with some areas (e.g., Wenchang and Haikou) experiencing emission hotspots in recent years. Higher yield and smaller CFa for Lingao and Tunchang were observed compared to the average between 2010 and 2020. This study provides insights into the spatiotemporal dynamics of double rice production and GHG emissions in Hainan, offering a scientific reference for regional food security and environmental sustainability.

Overexpression of human SAMD9 inhibits protein translation and alters MYC signaling resulting in cell cycle arrest.

Inherited bone marrow failure syndromes (iBMFS) often result from pathogenic mutations in genes that are important for ribosome function, namely, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita. Germline mutations in SAMD9 are a frequent genetic lesion resulting in an iBMFS with monosomy 7; some patients have severe multisystem syndromes that include myelodysplasia. The association of germline SAMD9 mutations and bone marrow failure is clear, but to date, there is no reliable method to predict if a novel SAMD9 mutation is pathogenic unless it is accompanied by an obvious family history and/or clinical syndrome. The difficulty with pathogenicity prediction is, in part, due to the incomplete understanding of the biological functions of SAMD9. We used a SAMD9-targeted, inducible CRISPRa system and RNA sequencing to better understand the global transcriptional changes that result from transcriptional manipulation of SAMD9. Supporting recent discoveries that SAMD9 acts as a ACNase specific for phenylalanine tRNA (tRNA-Phe), we confirmed with crosslinking and solid-phase purification (CLASP) that SAMD9 is an RNA binding protein and analyzed how overexpression of tRNA-Phe may reverse transcriptomic changes caused by SAMD9 activation. Our data show that overexpression of SAMD9 from the endogenous locus results in decreased cell proliferation, cell cycle progression, and global protein translation. When SAMD9 contains a gain-of-function mutation (p.E1136Q) these functional phenotypes are exacerbated, but only partially rescued with tRNA-Phe overexpression suggesting additional molecular actions of SAMD9. Additionally, we demonstrate that gene expression pathways important for ribosome biogenesis and MYC signaling are the most significantly impacted by SAMD9 overexpression.

Vegetation resilience assessment and its climatic driving factors: Evidence from surface coal mines in northern China.

Vegetation resilience is a key concept for understanding ecosystem responses to disturbances and is essential for maintaining ecosystem sustainability. However, assessing vegetation resilience remains challenging, especially for areas with significant disturbances and ecological restoration, such as surface coal mine ecosystems. Vegetation resilience assessment requires a combination of disturbance magnitude, recovery magnitude, and recovery time. In this study, we propose a vegetation resilience assessment method by integrating disturbance magnitude, recovery magnitude and recovery time. Forty-six surface coal mines in Northern China were analysed as the study areas. A geographical detector model was used to explore the influence of climatic factors on vegetation resilience. The results indicated that the vegetation resilience curves included three shapes, inverted U-shaped, S-shaped, and monotonically decreasing, and the different disturbance-recovery relationships of the curves indicated that natural and social factors jointly changed the ecological restoration process. The vegetation resilience of the 46 surface coal mines varies widely, ranging from 0.87 to 7.22, showing a spatial decreasing trend from east to west. The explanatory power of different climatic factors on vegetation resilience by indirectly affecting hydrothermal conditions varies, with the effect of atmospheric pressure being the most significant and the superposition of the two climatic factors enhancing the effect on vegetation resilience. This study enriches the understanding of vegetation resilience assessment and provides important information to guide the differentiation of ecological restoration and resource development of surface coal mines in different regions.

Bulk T-cell receptor sequencing confirms clonality in obstetric antiphospholipid syndrome and may as a potential biomarker.

The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRß repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.

Influence Factors of the Therapeutic Effect of Budesonide Combined with N-Acetylcysteine in Children with Mycoplasma Pneumoniae Infection Analyzed by Lasso-Logistic and Construction of a Nomogram Prediction Model.

Objective: This study aims to analyze the factors influencing the efficacy of budesonide (BUD) combined with N-acetylcysteine (NAC) treatment in children with Mycoplasma pneumoniae (MP) infection through Lasso-Logistic analysis, construct a Nomogram predictive model, and provide personalized treatment plans for clinicians. Additionally, it aims to fill the knowledge gap regarding the treatment of MP-infected children with BUD combined with NAC. Methods: We retrospectively analyzed clinical data from 96 children treated with BUD and NAC for MP infection at our hospital from January 2022 to May 2023. Treatment outcomes were categorized as good or poor. Logistic regression and Lasso-Logistic analysis were used to identify independent factors influencing outcomes and construct a predictive Nomogram model, which was validated through ROC curve analysis. Results: Logistic regression identified prolonged fever (≥7 days), high fever, and elevated levels of TNF-α, IL-6, and CRP as independent risk factors for poor outcomes. The Nomogram model, based on these factors, demonstrated excellent predictive accuracy with a C-index of 0.992 and AUC values of 0.987 and 0.948 in the modeling and validation cohorts, respectively. Conclusion: The developed Nomogram model provides clinicians with a reliable tool to predict poor treatment outcomes in children with MP infection treated with BUD and NAC, supporting more personalized and effective treatment plans.

The temperature dependence of the Hildebrand solubility parameters of selected hydrocarbon polymers and hydrocarbon solvents: a molecular dynamics investigation.

CONTEXT: To determine the miscibility of liquids at high temperatures using the concept of Hildebrand solubility parameter δ , the current practice is to examine the difference in δ between two liquids at room temperature, assuming that δ is not sensitive to temperature. However, such an assumption may not be valid for certain polymer blends and solutions. Therefore, a knowledge of the δ values of the liquids of interest at high temperatures is desirable. The determination of δ at high temperatures, especially for high-molecular-weight polymers, is impossible, as polymers have vapor pressures of zero. To this end, molecular dynamics (MD) simulations provide a practical means for determining δ over a wide range of temperatures. In this work, we study the temperature dependence of δ of five hydrocarbon polymers: polyethylene (PE), isotactic and atactic polypropylene (i-PP and a-PP), polyisobutylene (PIB), and polyisoprene (PI) in five hydrocarbon solvents: n-pentane, n-hexane, n-dodecane, isobutene, and cyclohexane. The polymers are modeled as monodisperse chains with 100 repeat units. The average δ values of PE, i-PP, a-PP, PIB, and PI at 300 K are determined as 18.6, 14.9, 14.6, 14.3, and 16.4 MPa1/2, respectively, in a good agreement with experimental data. The δ values of these polymers at various temperatures are also determined. The temperature dependence of δ is fitted to two linear equations, one above and the other below the polymer's glass transition temperature Tg. The δ values are more sensitive to temperature at T ≥ Tg. The Tg values of the polymers, determined based upon their specific volumes and δ values agree with the experiment qualitatively. The determination of the temperature dependence of δ has a great potential for industrial applications, such as determining miscibility, developing polymeric organogelators as flocculants and oil spill treating agents, and identifying potential solvents and ideal processing temperatures. METHODS: The MD simulations are performed using the GROMACS 2022.3 package with optimized potential for liquid simulations-all atom (OPLS-AA) force field parameters. All polymers are built as extended chains using CHARMM-GUI Polymer Builder.

The tRNA Gm18 methyltransferase TARBP1 promotes hepatocellular carcinoma progression via metabolic reprogramming of glutamine.

Cancer cells rely on metabolic reprogramming to sustain the prodigious energetic requirements for rapid growth and proliferation. Glutamine metabolism is frequently dysregulated in cancers and is being exploited as a potential therapeutic target. Using CRISPR/Cas9 interference (CRISPRi) screening, we identified TARBP1 (TAR (HIV-1) RNA Binding Protein 1) as a critical regulator involved in glutamine reliance of cancer cell. Consistent with this discovery, TARBP1 amplification and overexpression are frequently observed in various cancers. Knockout of TARBP1 significantly suppresses cell proliferation, colony formation and xenograft tumor growth. Mechanistically, TARBP1 selectively methylates and stabilizes a small subset of tRNAs, which promotes efficient protein synthesis of glutamine transporter-ASCT2 (also known as SLC1A5) and glutamine import to fuel the growth of cancer cell. Moreover, we found that the gene expression of TARBP1 and ASCT2 are upregulated in combination in clinical cohorts and their upregulation is associated with unfavorable prognosis of HCC (hepatocellular carcinoma). Taken together, this study reveals the unexpected role of TARBP1 in coordinating the tRNA availability and glutamine uptake during HCC progression and provides a potential target for tumor therapy.

H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING-TBK1 pathway.

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.

Quantitative skin surface hydration measurement by visible optical image processing: A pilot study.

BACKGROUND: Skin barrier function is significantly impacted by skin moisture. Most non-invasive evaluation techniques to measure skin surface hydration relying on its electrical properties, which are limited in scope and have unstable operations. Applying image processing for skin hydration assessment is uncommon, with an emphasis on skin-capacitive pictures and near-infrared images in general, which demand a certain spectrum. As a result, there is an increasing need for wide-area skin hydration evaluation and mapping. OBJECTIVE: The study aims to propose a quantitative evaluation algorithm for skin surface hydration from visible-light images. MATERIALS AND METHODS: Three devices were applied to measure skin hydration: skin image capture device and two recognized commercial skin devices. A digital image processing system creates a new index, called GVR, to symbolize skin surface moisture. The CLAHE algorithm was applied to enhance the contrast of skin image, and after calculating it with the monochrome image, the skin reflectance image was segmented. The GVR was estimated using the values of the individual sites and the entire skin. The correlation coefficient between the three methods was examined using statistical analysis to assess the performance of GVR. RESULTS: Skin hydration estimated from visible-light images is influenced by the entire facial structure in addition to specific areas. The electrical and visible image evaluations showed a strong association with a significant difference. CONCLUSION: It was discovered that reflecting measures from visible images provide a quick and efficient way to quantify the moisture of the skin's surface.

Advanced MXene-based materials for efficient extraction of uranium from seawater and wastewater.

In order to realize the low-carbon development policy, the large-scale development and utilization of nuclear energy is very essential. Uranium is the key resource for nuclear industry. The extracting and recycling uranium from seawater and nuclear wastewater is necessary for secure uranium reserves, ensure energy security, control pollution and protect the environment. The novel nanomaterial MXene possesses the layered structure, high specific surface area, and modifiable surface terminal groups, which allowed it to enrich uranium. In addition, good photovoltaic and photothermal properties improves the ability to adsorb uranium. The excellent radiation resistance of the MAX phase strongly indicates the potential use of MXene as an effective uranium adsorbent. However, there are relatively few reviews on its application in uranium extraction and recovery. This review focuses on the recent advances in the use of MXene-based materials as highly efficient adsorbents for the recovery of uranium from seawater and nuclear wastewater. First, the structural, synthetic and characterization aspects of MXene materials are introduced. Subsequently, the adsorptive properties of MXene-based materials are evaluated in terms of uranium extraction recovery capability, selectivity, and reproducibility. Furthermore, the interaction mechanisms between uranium and MXene absorbers are discussed. Finally, the challenges for MXene materials in uranium adsorption applications are proposed for better design of new types of MXene-based adsorbents.

Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study.

Background: The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated. Methods: Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships. Results: There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings. Conclusions: There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.

Combined nutritional status and activities of daily living disability is associated with one-year mortality after hip fracture surgery for geriatric patients: a retrospective cohort study.

OBJECTIVE: We aimed to explore the association combined nutritional status and activities of daily living disability with all-cause mortality of older adults with hip fracture in the first year after hospitalization. METHODS: This is a single-center retrospective cohort study in older adults with hip fracture patients. Clinical data and laboratory results were collected from electronic medical record system of our hospital (2014-2021). The endpoint of this study was all-cause mortality in the first year after hospitalization. RESULTS: A total of 303 older adults were enrolled and all-cause mortality was 21.8%. The study population was categorized by CONUT score. Patients in CONUT score 5-12 had a higher age, ASA status, CRP and creatinine level, more patients with history of fracture, pneumonia and delirium, meanwhile, lower BMI and ADL score, lower hemoglobin, lymphocyte, total protein, albumin, triglyceride, total cholesterol and one year survival than those in CONUT score 0-4 (all P < 0.05). Multivariable Cox analysis showed that BMI, ADL score and CONUT score were independent risk factors for all-cause mortality of hip fracture in older adults (HR (95% CI):2.808(1.638, 4.814), P < 0.001; 2.862(1.637, 5.003), P < 0.001; 2.322(1.236, 4.359), P = 0.009, respectively). More importantly, the combined index of CONUT and ADL score had the best predictive performance based on ROC curve (AUC 0.785, 95% CI: 0.734-0.830, P < 0.0001). Kaplan-Meier survival curves for all-cause mortality showed that patients with CONUT score increase and ADL score impairment had a higher mortality rate at 1 year compared to CONUT score decrease and ADL score well (Log Rank χ2 = 45.717, P < 0.0001). CONCLUSIONS: Combined CONUT and ADL score is associated with one-year mortality after hip fracture surgery for geriatric patients.

Oral oxytocin blurs sex differences in amygdala responses to emotional scenes.

BACKGROUND: The sex differences were co-shaped by innate biological differences and social environment, and were frequently observed in human emotional neural responses. Oral administration of oxytocin, as an alternative and noninvasive intake method, has been demonstrated to produce sex-dependent effects on emotional face processing. However, it is unclear whether oral oxytocin produces similar sex-dependent effects on processing continuous emotional scenes. METHODS: Current randomized, double-blind, placebo-controlled neuro-psychopharmacological fMRI experiment was conducted in 147 healthy participants (oxytocin=74, male/female=37/37; placebo=73, male/female=36/37) to examine the oral oxytocin effect on plasma oxytocin concentrations and neural response to emotional scenes in both sexes. RESULTS: At the neuroendocrine level, females showed lower endogenous oxytocin concentrations than males, but oral oxytocin equally increased the oxytocin concentrations in both sexes. Regarding neural activity, emotional scenes evoked opposite valence-independent effects on right amygdala activation (females>males) and its functional connectivity with the insula (males>females) in two sexes in the placebo group. This sex difference were either attenuated (amygdala response) or even completely eliminated (amygdala-insula functional connectivity) in the oxytocin group. The multivariate pattern analysis confirmed these findings by developing an accurate sex-predictive neural pattern that including the amygdala and the insula under the placebo but not oxytocin condition. CONCLUSION: Present study suggests a pronounced sex-difference in neural responses to emotional scenes which is abolished by oral oxytocin, with it having opposite modulatory effects in two sexes. Possibly this may reflect oral OXT enhancing emotional regulation to continuous emotional stimuli in both sexes by facilitating appropriate changes in sex-specific amygdala-insula circuitry.

The role of ultraviolet radiation in the flavor formation during drying processing of Pacific saury (Cololabis saira).

BACKGROUND: Traditional sun-drying aquatic products are popular and recognized by customers, owing to their unique flavor and long-term preservation. However, the product quality and production efficiency cannot be guaranteed. Cololabis saira is rich in unsaturated fatty acids, which are susceptible to hyperoxidation during the drying process. This study aimed to make clear the role of ultraviolet (UV) radiation in flavor formation during drying processes of Cololabis saira to develop a modern drying technology. RESULTS: Lipid oxidation analysis revealed that moderate hydrolytic oxidation occurred in the UV-assisted cold-air drying group due to the combined influence of UV and cold-air circulation, resulting in the thiobarbituric acid reactive substances value being higher than that of cold-air drying group but lower than the natural drying group. Hexanal, heptanal, cis-4-heptenal, octanal, nonanal, (trans,trans)-2,4-heptadienal, (trans,trans)-2,6-nonanedial, 1-octen-3-ol, heptanol, 2,3-pentanedione, 3,5-octadien-2-one and trimethylamine were identified as the characteristic flavor odor-active compounds present in all Cololabis saira samples. Yet, during the natural drying process, sunlight promoted the lipid oxidation, resulting in the highest degree of lipid oxidation among three drying methods. Light and heat promoted lipid oxidation in Cololabis saira prepared through natural drying process, leading to a large accumulation of volatile compounds, such as 3-methylbutyraldehyde, 2,3-pentanedione, 1-propanol, and 3-pentanone. Cold air circulation inhibited lipid oxidation to some extent, resulting in a blander flavor profile. More cis-4-heptenal, cis-2-heptenal, octanal and 2-ethylfuran accumulated during the UV-assisted cold-air drying process, enriching its greasy flavor and burnt flavor. CONCLUSION: UV-assisted cold-air drying could promote moderate lipid oxidation, which is beneficial for improving product flavor. To sum up, UV radiation played a crucial role in the flavor formation during the drying process of Cololabis saira. © 2024 Society of Chemical Industry.