Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors.

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Advancements in Gellan Gum-Based Films and Coatings for Active and Intelligent Packaging.

Gellan gum (GG) is a natural polysaccharide with a wide range of industrial applications. This review aims to investigate the potential of GG-based films and coatings to act as environmentally friendly substitutes for traditional petrochemical plastics in food packaging. GG-based films and coatings exhibit versatile properties that can be tailored through the incorporation of various substances, such as plant extracts, microorganisms, and nanoparticles. These functional additives enhance properties like the light barrier, antioxidant activity, and antimicrobial capabilities, all of which are essential for extending the shelf-life of perishable food items. The ability to control the release of active compounds, along with the adaptability of GG-based films and coatings to different food products, highlights their effectiveness in preserving quality and inhibiting microbial growth. Furthermore, GG-based composites that incorporate natural pigments can serve as visual indicators for monitoring food freshness. Overall, GG-based composites present a promising avenue for the development of sustainable and innovative food packaging solutions.

Association of healthy lifestyles with risk of all-cause and cause-specific mortality among individuals with metabolic dysfunction-associated steatotic liver disease: results from the DFTJ cohort.

AIM: To examine the associations of healthy lifestyles with risk of all-cause and cause-specific mortality among adults with metabolic dysfunction-associated steatotic liver disease (MASLD), and whether the association was mediated by systemic immune-inflammatory biomarkers (SIIBs). METHODS: The study included 10,347 subjects with MASLD, who were enrolled in the Dongfeng-Tongji cohort study. The healthy lifestyles referred to non-smoking, being physically active (≥7.5 metabolic equivalents-hours/week), low-risk alcohol consumption (1-14 g/day for women and 1-28 g/day for men), and optimal sleep duration (≥6 to ≤8 h/day). Cox proportional hazard models were used to examine the relationship between each lifestyle and SIIBs with the risk of all-cause and cause-specific mortality. A mediation analysis was conducted to investigate the role of SIIBs on the association between healthy lifestyles and mortality. RESULTS: There were 418 MASLD subjects dead till the follow-up of 2018, including 259 deaths from cardiovascular disease (CVD). Compared to MASLD participants with 0-1 healthy lifestyle score (HLS), those with 3-4 HLS had the lowest risk of all-cause mortality [hazard ratio (HR), 0.46; 95% CI, (0.36-0.60)], and CVD mortality [HR (95%CI), 0.41 (0.29-0.58)]. Mediation analyses indicated that SIIBs mediated the association between healthy lifestyles and mortality, with proportions ranging from 2.5% to 6.1%. CONCLUSIONS: These findings suggest that adherence to healthy lifestyles can significantly reduce mortality for MASLD patients, and the decreased SIIBs may partially explain the protection mechanism of healthy lifestyles.

A Study on AIDS Self-Management Status and Its Influencing Factors.

Purpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies. Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA. Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA's place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05). Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.

Associations between multiple metals exposure and cognitive function in the middle-aged and older adults from China: A cross-sectional study.

The rapidly rising risk of cognitive decline is a serious challenge for the elderly. As the wide-distributed environmental chemicals, the effects of metals exposure on cognitive function have attracted much attention, but the results remain inclusive. This study aimed to investigate the roles of multiple metals co-exposure on cognition. We included a total of 6112 middle-aged and older participants, detected their plasma levels of 23 metals by using inductively coupled plasma mass spectrometry, and assessed their cognitive function by using the Mini-Mental State Examination (MMSE). The results showed that increased plasma levels of iron (Fe) and zinc (Zn) were positively associated with MMSE score, but the increased levels of nickel (Ni) and lead (Pb) were associated with decreased MMSE score (all FDR < 0.05). Subjects exposed to both high levels of Ni and Pb showed the lowest MMSE score [ß (95% CI) = -0.310 (-0.519, -0.100)], suggesting that Ni and Pb had a synergistic toxic effect on cognitive function. In addition, the hazardous roles of Ni and Pb were mainly found among subjects with low plasma level of Zn, but were not significant among those with high-Zn level [Ni: ß (95% CI) = -0.281 (-0.546, -0.015) vs. -0.146 (-0.351, 0.058); Pb: ß (95% CI) = -0.410 (-0.651, -0.169) vs. -0.060 (-0.275, 0.155)], which suggested that Zn could attenuate the adverse effects of Pb and Ni on cognitive function. The cognitive function was gradually decreased among subjects with increased number of adverse exposures to the above four metals (Ptrend < 0.001). In conclusion, our findings revealed the individual, interactive, and combined effects of Fe, Ni, Pb, and Zn on cognitive function, which may provide new perspectives on cognitive protection, but further prospective cohort studies and biological researches are needed to validate these findings.

TRPC3/6 Channels Mediate Mechanical Pain Hypersensitivity via Enhancement of Nociceptor Excitability and of Spinal Synaptic Transmission.

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

Pretreatment Computed Tomography-Defined Sarcopenia, Treatment-Associated Muscle Loss, and Survival in Patients With Cervical Cancer: A Systematic Review and Meta-Analysis.

CONTEXT: Sarcopenia has been identified as a potential predictor of poor prognosis in various types of cancer. However, the impact of pretreatment sarcopenia and the reduction of skeletal muscle mass during treatment on survival outcomes of patients with cervical cancer is still not well understood. OBJECTIVE: This meta-analysis was conducted to investigate the impact of pretreatment sarcopenia and treatment-associated muscle loss on survival outcomes in patients with cervical cancer. DATA SOURCES: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies exploring the relationship between muscle loss and the prognosis of cervical cancer until January 1, 2023. DATA EXTRACTION: The hazard ratios (HRs) and 95% CIs for overall survival (OS) and progression-free survival (PFS) were extracted. DATA ANALYSIS: The data were analyzed using R software. The studies' quality was assessed using the Quality in Prognostic Studies tool. Twelve observational studies involving 1498 patients with cervical cancer were included in the analysis, with a prevalence of sarcopenia ranging from 24.8% to 57.5%. Sarcopenia was an independent predictor of poor OS (HR, 1.68; 95% CI, 1.28-2.21; P < .01) and PFS (HR, 1.53; 95% CI, 1.19-1.98; P < .01) in patients with cervical cancer. Additionally, the decrease in skeletal muscle during treatment was also significantly related to the OS (HR, 4.46; 95% CI, 2.87-6.94; P < .01) and PFS (HR, 2.89; 95% CI. 1.83-4.55; P < .01). CONCLUSIONS: The prevalence of pretreatment sarcopenia was high among patients with cervical cancer. Pretreatment sarcopenia and skeletal muscle loss during treatment both negatively affected prognosis in cervical cancer.

A mannose-rich exopolysaccharide-1 isolated from Bifidobacterium breve mitigates ovalbumin-induced intestinal damage in mice by modulation CD4 + T cell differentiation and inhibiting NF-κB signaling pathway.

Ovalbumin (OVA)-induced intestinal injury is a recurrent and potentially fatal condition. Previous studies have highlighted the roles of exopolysaccharides, particularly a mannose-rich (89.59 %) exopolysaccharide-1 (EPS-1) with a molecular weight of 39.9 kDa, isolated from Bifidobacterium breve H4-2, in repairing intestinal barriers and regulating immune responses. In this study, a mouse model of OVA-induced intestinal injury was used to investigate the effects of EPS-1 on intestinal barrier restoration. The results demonstrated that EPS-1 treatment (400 mg/kg. d) significantly reduced the allergic index (3.25 ± 0.43) in OVA-challenged mice (p < 0.05), improved the physical integrity of the intestinal barrier by increasing mucin content and goblet cell number in the ileum (p < 0.05). EPS-1 treatment (400 mg/kg. d) also maintained immune barrier integrity by restoring imbalanced CD4 + T/CD8 + T ratios from 0.86 ± 0.02 to 1.04 ± 0.06, regulating Th1/Th2 and Th17/Treg cells balance, as well as inhibited the NF-κB signaling pathway. Furthermore, EPS-1 maintained microbiota homeostasis by increasing the abundances of Ruminococcus, Butyricicoccus, and Muribaculaceae, while reducing Streptococcus and Candidatus arthromitus. This microbiota modulation enhanced the levels of metabolites such as tyrosine, methionine, tryptophan, triglycerides, and salidroside. In conclusion, EPS-1 shows promise as a functional polysaccharide for therapeutic use.

Genome-wide DNA methylation profiling in blood reveals epigenetic signature of incident acute coronary syndrome.

DNA methylation (DNAm) has been implicated in acute coronary syndrome (ACS), but the causality remains unclear in cross-sectional studies. Here, we conduct a prospective epigenome-wide association study of incident ACS in two Chinese cohorts (discovery: 751 nested case-control pairs; replication: 476 nested case-control pairs). We identified and validated 26 differentially methylated positions (DMPs, false discovery rate [FDR] <0.05), including three mapped to known cardiovascular disease genes (PRKCZ, PRDM16, EHBP1L1) and four with causal evidence from Mendelian randomization (PRKCZ, TRIM27, EMC2, EHBP1L1). Two hypomethylated DMPs were negatively correlated with the expression in blood of their mapped genes (PIGG and EHBP1L1), which were further found to overexpress in leukocytes and/or atheroma plaques. Finally, our DMPs could substantially improve the prediction of ACS over traditional risk factors and polygenic scores. These findings demonstrate the importance of DNAm in the pathogenesis of ACS and highlight DNAm as potential predictive biomarkers and treatment targets.

Physiological, Metabolome and Gene Expression Analyses Reveal the Accumulation and Biosynthesis Pathways of Soluble Sugars and Amino Acids in Sweet Sorghum under Osmotic Stresses.

Water scarcity is a major environmental constraint on plant growth in arid regions. Soluble sugars and amino acids are essential osmolytes for plants to cope with osmotic stresses. Sweet sorghum is an important bioenergy crop and forage with strong adaptabilities to adverse environments; however, the accumulation pattern and biosynthesis basis of soluble sugars and amino acids in this species under osmotic stresses remain elusive. Here, we investigated the physiological responses of a sweet sorghum cultivar to PEG-induced osmotic stresses, analyzed differentially accumulated soluble sugars and amino acids after 20% PEG treatment using metabolome profiling, and identified key genes involved in the biosynthesis pathways of soluble sugars and amino acids using transcriptome sequencing. The results showed that the growth and photosynthesis of sweet sorghum seedlings were significantly inhibited by more than 20% PEG. After PEG treatments, the leaf osmotic adjustment ability was strengthened, while the contents of major inorganic osmolytes, including K+ and NO3-, remained stable. After 20% PEG treatment, a total of 119 and 188 differentially accumulated metabolites were identified in the stems and leaves, respectively, and the accumulations of soluble sugars such as raffinose, trehalose, glucose, sucrose, and melibiose, as well as amino acids such as proline, leucine, valine, serine, and arginine were significantly increased, suggesting that these metabolites should play key roles in osmotic adjustment of sweet sorghum. The transcriptome sequencing identified 1711 and 4978 DEGs in the stems, as well as 2061 and 6596 DEGs in the leaves after 20% PEG treatment for 6 and 48 h, respectively, among which the expressions of genes involved in biosynthesis pathways of sucrose (such as SUS1, SUS2, etc.), trehalose (including TPS6), raffinose (such as RAFS2 and GOLS2, etc.), proline (such as P5CS2 and P5CR), leucine and valine (including BCAT2), and arginine (such as ASS and ASL) were significantly upregulated. These genes should be responsible for the large accumulation of soluble sugars and amino acids under osmotic stresses. This study deepens our understanding of the important roles of individual soluble sugars and amino acids in the adaptation of sweet sorghum to water scarcity.

Development of pectin/chitosan-based electrospun biomimetic nanofiber membranes loaded with dihydromyricetin inclusion complexes for wound healing application.

Accidents and surgical procedures inevitably lead to wounds, presenting clinical challenges such as inflammation and microbial infections that impede the wound-healing process. This study aimed to address these challenges by developing a series of novel wound dressings known as electrospun biomimetic nanofiber membranes. These membranes were prepared using electrostatic spinning technique, incorporating hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes. The prepared electrospun biomimetic nanofiber membranes exhibited randomly arranged fiber morphology with average fiber diameters ranging from 200 to 400 nm, resembling the collagen fibers in the native skin. These membranes demonstrated excellent biocompatibility, hemocompatibility, surface hydrophilicity, and wettability, while also releasing dihydromyricetin in a sustained manner. In vitro testing revealed that these membranes, loaded with hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes, displayed higher antioxidant potential and inhibitory effects against Staphylococcus aureus and Escherichia coli. Furthermore, these membranes significantly reduced the M1 phenotypic transition in RAW264.7 cells, even when stimulated by lipopolysaccharides, effectively restoring M2 polarization, thereby shortening the inflammatory period. Additionally, the in vivo wound healing effects of these membranes were validated. In conclusion, this study introduces a promising nanofiber membrane with diverse biological properties that holds promise for addressing various crucial aspects of the wound-healing process.

Genetic predisposition to impaired beta-cell function modifies the association between serum pyrethroid levels and the risk of type 2 diabetes: A gene-environment interaction study.

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98-1.56) and 0.91 (0.77-1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02-1.47) and 0.95 (0.78-1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03-7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78-5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

Symmetry in thermal cycles and processes.

Symmetry analysis is a cutting-edge research approach in physics, yet its application in macroscopic energy systems remains limited. This study demonstrates its potential to provide valuable insights for a deeper understanding and development of thermodynamic cycles. This article first studies the symmetry of the proposed C-P diagrams and finds rich symmetries including reflection symmetry, translation symmetry, and rotational symmetry within Carnot cycles. Then, it emphasizes that one can use symmetry alone to prove that the highest efficiency for any cycle operating in a certain temperature range is the Carnot efficiency, without relying on the entropy concept in the second law of thermodynamics. Lastly, it is found that this symmetry analysis framework can also be used for thermal cycles with phase transitions, as exemplified by applying in Rankine cycles. This research not only contributes groundbreaking insights into unraveling the symmetry inherent in thermodynamic cycles, but also promotes symmetry analysis to be an alternative analysis mean.

Comparative Physiological and Gene Expression Analyses Reveal Mechanisms Involved in Maintaining Photosynthesis Capacity, Alleviating Ion Toxicity and Oxidative Stress of Kentucky Bluegrass under NaCl Treatment.

Kentucky bluegrass (Poa pratensis L.), a widely used cool-season turfgrass, shows a high sensitivity to soil salinity. Clarifying the adaptative mechanisms of Kentucky bluegrass that serve to improve its salt tolerance in saline environments is urgent for the application of this turfgrass in salt-affected regions. In this study, physiological responses of the Kentucky bluegrass cultivars "Explorer" and "Blue Best" to NaCl treatment, as well as gene expressions related to photosynthesis, ion transport, and ROS degradation, were analyzed. The results showed that the growth of "Explorer" was obviously better compared to "Blue Best" under 400 mM NaCl treatment. "Explorer" exhibited a much stronger photosynthetic capacity than "Blue Best" under NaCl treatment, and the expression of key genes involved in chlorophyll biosynthesis, photosystem II, and the Calvin cycle in "Explorer" was greatly induced by salt treatment. Compared with "Blue Best", "Explorer" could effectively maintain Na+/K+ homeostasis in its leaves under NaCl treatment, which can be attributed to upregulated expression of genes, such as HKT1;5, HAK5, and SKOR. The relative membrane permeability and contents of O2- and H2O2 in "Explorer" were significantly lower than those in "Blue Best" under NaCl treatment, and, correspondingly, the activities of SOD and POD in the former were significantly higher than in the latter. Moreover, the expression of genes involved in the biosynthesis of enzymes in the ROS-scavenging system of "Explorer" was immediately upregulated after NaCl treatment. Additionally, free proline and betaine are important organic osmolytes for maintaining hydration status in Kentucky bluegrass under NaCl treatment, as the contents of these metabolites in "Explorer" were significantly higher than in "Blue Best". This work lays a theoretical basis for the improvement of salt tolerance in Kentucky bluegrass.

TaNAC1 boosts powdery mildew resistance by phosphorylation-dependent regulation of TaSec1a and TaCAMTA4 via PP2Ac/CDPK20.

The integrity of wheat (Triticum aestivum) production is increasingly jeopardized by the fungal pathogen Blumeria graminis f. sp. tritici (Bgt), particularly amid the vicissitudes of climate change. Here, we delineated the role of a wheat transcription factor, TaNAC1, which precipitates cellular apoptosis and fortifies resistance against Bgt. Utilizing BiFC, co-immunoprecipitation, protein quantification, luciferase report assays, we determined that cytoplasmic TaNAC1-7A undergoes phosphorylation at the S184/S258 sites by TaCDPK20, facilitating its nuclear translocation. This migration appears to prime further phosphorylation by TaMPK1, thereby enhancing transcriptional regulatory activity. Notably, the apoptotic activity of phosphorylated TaNAC1-7A is negatively modulated by the nuclear protein phosphatase PP2Ac. Furthermore, activation of TaNAC1 phosphorylation initiates transcription of downstream genes TaSec1a and TaCAMTA4, through binding to the C[T/G]T[N7]A[A/C]G nucleic acid motif. Suppression of TaNAC1, TaCDPK20, and TaMPK1 in wheat compromises its resistance to Bgt strain E09, whereas overexpression of TaNAC1 and silencing of PP2Ac markedly elevate resistance levels. Our results reveal the pivotal role of TaNAC1 in basal resistance which is mediated by its effects on homotypic fusion, vacuolar protein sorting, and the expression of defense-related genes. The findings highlight the potential through targeting TaNAC1 and its regulators as a strategy for improving wheat's resistance to fungal pathogens.

Associations of ambient air pollution exposure and lifestyle factors with incident dementia in the elderly: A prospective study in the UK Biobank.

OBJECTIVE: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. METHODS: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. RESULTS: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standarddeviationincrease in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer's disease (AD), but no significant modification effects are found for sleep patterns or smoking status. CONCLUSION: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.

Development of apple pectin/soy protein isolate-based edible films containing punicalagin for strawberry preservation.

In this study, we developed punicalagin-loaded antimicrobial films based on soy protein isolate (SPI) and apple pectin (AP). The AP was derived from apple pomace waste while the punicalagin was obtained from pomegranate peel. Punicalagin was identified to exist in both α- and ß-isomers, with the ß-type being predominant. The composite films were characterized using scanning electron microscopy, Fourier transformed infrared spectroscopy, X-ray diffraction, and thermogravimetric analysis. Our results demonstrated that the incorporation of AP significantly enhanced the mechanical strength, heat resistance, and barrier properties of the films. Moreover, the composite films integrated with punicalagin exhibited excellent antimicrobial activities against Staphylococcus aureus (with a minimum bactericidal concentration value of 0.25 %), Escherichia coli (with a minimum bactericidal concentration value of 0.50 %), and Aspergillus niger. Finally, these antimicrobial film solutions were tested as coatings on strawberries and found to have significantly better effects on reducing weight loss, improving shelf-life, and maintaining the freshness of strawberries compared to coatings without punicalagin. The results indicate that antimicrobial coatings loaded with punicalagin hold great promise as multifunctional active packaging materials for fruit preservation.

Identification of nuclear membrane SUN proteins and components associated with wheat fungal stress responses.

In eukaryotes, the nuclear membrane that encapsulates genomic DNA is composed of an inner nuclear membrane (INM), an outer nuclear membrane (ONM), and a perinuclear space. SUN proteins located in the INM and KASH proteins in the ONM form the SUN-KASH NM-bridge, which functions as the junction of the nucleocytoplasmic complex junction. Proteins containing the SUN domain showed the highest correlation with differentially accumulated proteins (DAPs) in the wheat response to fungal stress. To understand the characteristics of SUN and its associated proteins in wheat responding to pathogen stress, here we investigated and comprehensive analyzed SUN- and KASH-related proteins among the DAPs under fungi infection based on their conserved motifs. In total, four SUN proteins, one WPP domain-interacting protein (WIP), four WPP domain-interacting tail-anchored proteins (WIT), two WPP proteins and one Ran GTPase activating protein (RanGAP) were identified. Following transient expression of Nicotiana benthamiana, TaSUN2, TaRanGAP2, TaWIT1 and TaWIP1 were identified as nuclear membrane proteins, while TaWPP1 and TaWPP2 were expressed in both the nucleus and cell membrane. RT-qPCR analysis demonstrated that the transcription of TaSUN2, TaRanGAP2 and TaWPP1 were strongly upregulated in response to fungal infection. Furthermore, using the bimolecular fluorescence complementation, the luciferase complementation and a nuclear and split-ubiquitin-based membrane yeast two-hybrid systems, we substantiated the interaction between TaSUN2 and TaWIP1, as well as TaWIP1/WIT1 and TaWPP1/WPP2. Silencing of TaSUN2, TaRanGAP2 and TaWPP1 in wheat leaves promoted powdery mildew infection and hyphal growth, and reduced the expression of TaBRI1, TaBAK1 and Ta14-3-3, indicating that these NM proteins play a positive role in resistance to fungal stress. Our study reveals the characteristics of NM proteins and propose the preliminary construction of SUN-WIP-WPP-RanGAP complex in wheat, which represents a foundation for detail elucidating their functions in wheat in future.

Solvent-Free Enzymatic Synthesis of Ethyl 3-Oxobutyrate Derivative: Characterization and Optimization of Reaction Condition.

It was first found that porcine pancreatic lipase (PPL) could catalyze the Knoevenagel condensation of aromatic aldehydes and ethyl acetoacetate under solvent-free conditions in this paper. Under solvent-free conditions, the highest yield of PPL catalytic reaction was 99.38%, and the Z/E selectivity of the product was 3.93. In addition, the reaction conditions were optimized, and the factors affecting the product structure were studied.

Mitochondrial DNA copy number mediated the associations between perfluoroalkyl substances and breast cancer incidence: A prospective case-cohort study.

Epidemiologic studies have reported the relationships between perfluoroalkyl substances (PFASs) and breast cancer incidence, yet the underlying mechanisms are not well understood. This study aimed to elucidate the mediation role of mitochondrial DNA copy number (mtDNAcn) in the relationships between PFASs exposure and breast cancer risk. We conducted a case-cohort study within the Dongfeng-Tongji cohort, involving 226 incident breast cancer cases and a random sub-cohort (n = 990). Their plasma concentrations of six PFASs [including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)], and peripheral blood levels of mtDNAcn, were detected at baseline by using ultraperformance liquid chromatography-tandem mass spectrometry and quantitative real-time PCR, respectively. Linear regression and Barlow-weighted Cox models were employed separately to assess the relationships of mtDNAcn with PFASs and breast cancer risk. Mediation analysis was further conducted to quantify the mediating effects of mtDNAcn on PFAS-breast cancer relationships. We observed increased blood mtDNAcn levels among participants with the highest PFNA and PFHpA exposure [Q4 vs. Q1, ß(95%CI) = 0.092(0.022, 0.162) and 0.091(0.022, 0.160), respectively], while no significant associations were observed of PFOA, PFDA, PFOS, or PFHxS with mtDNAcn. Compared to participants within the lowest quartile subgroup of mtDNAcn, those with the highest mtDNAcn levels exhibited a significantly increased risk of breast cancer and postmenopausal breast cancer [Q4 vs. Q1, HR(95%CI) = 3.34(1.80, 6.20) and 3.71(1.89, 7.31)]. Furthermore, mtDNAcn could mediate 14.6 % of the PFHpA-breast cancer relationship [Indirect effect, HR(95%CI) = 1.02(1.00, 1.05)]. Our study unveiled the relationships of PFNA and the short-chain PFHpA with mtDNAcn and the mediation role of mtDNAcn in the PFHpA-breast cancer association. These findings provided insights into the potential biological mechanisms linking PFASs to breast cancer risk.