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Objective To investigate the effect of temperature variability on ischemic heart disease (IHD) mortality and to provide a scientific basis for disease prevention and control strategies. Methods Age-standardized mortality rates (ASMRs) for temperature-related IHD were extracted from the Global Burden of Disease 2021 database. Joinpoint regression was used to analyze the trend of the ASMRs. Age-period-cohort (APC) models were used to analyze independent age, period and cohort effects. Bayesian APC model was used to project ASMRs into the next 30 years. Results From 1990 to 2021, ASMR of IHD related to low temperature decreased with time. However, ASMR related to high temperature demonstrated a gradual increase, though was still lower than ASMR related to low temperature. ASMR was higher in males than in females. Age, period and cohort effects were dominant in the risk of death related to temperature. Low temperature associated ASMR was higher in high and high-middle socio-demographic index (SDI) regions, but declined more rapidly than other SDI regions over time. Except for high SDI regions, high temperatures in other regions tended to increase ASMR. Pakistan, Montenegro and Lesotho were the countries with the largest increases in ASMR related to low temperatures. The largest increases in ASMR related to high temperatures were observed in Egypt, Iraq and Saudi Arabia. Projections indicated that the risk of high temperature-induced mortality would continue to increase over time. Conclusions IHD deaths associated with temperature variability are heterogeneous, with low temperature leading to a decreased risk of death and high temperature being a significant factor contributing to the continued increase in mortality risk.

Synthetic cannabinoids (SCs) are a rapidly developing kind of novel psychoactive substance, frequently associated with acute intoxication and public health concerns. This study aimed to elucidate and compare the phase I metabolic pathways of two structurally related SCs, 5F-ADB-PINACA and 5F-ADBICA, using in vitro and in vivo models. Temporal metabolic profiling was performed to identify potential signature metabolites. Temporal abundance patterns and correlation cluster analysis of metabolites were analyzed to determine metabolite biomarkers. The two SCs were incubated with pooled human liver microsomes for 24 h and were also evaluated in vivo in zebrafish. Metabolite profiles were characterized using UHPLC-QE Orbitrap-MS. HLM analysis identified 21 5F-ADB-PINACA metabolites and 28 5F-ADBICA metabolites. Metabolites of 5F-ADBICA were detected for the first time in vitro and in a zebrafish model. Zebrafish studies confirmed the presence of all key metabolites observed in HLM. Comparative analysis of their metabolic pathways revealed differences in metabolism driven by structural differences between the indazole and indole cores. This is the first time that correlation analysis has been used in the temporal metabolic profiling of SCs. This study comprehensively characterized the metabolism of 5F-ADB-PINACA and 5F-ADBICA, identifying M13 (hydrolytic defluorination) as a potential metabolite biomarker for 5F-ADB-PINACA and M19 (hydrolytic defluorination) as a potential metabolite biomarker for 5F-ADBICA. The metabolic reactions of the main metabolites of the two synthetic cannabinoids are consistent. However, their metabolic processes (i.e., the overall metabolic pathways and temporal progression of these reactions) are different, which illustrates the metabolic similarity of structurally similar synthetic cannabinoids and the impact of different structures on the metabolic processes.

Bladder cancer (BC) represents a paradigm of infection-associated malignancy in which microbial dysbiosis, immune aging, and tumor microenvironmental remodeling converge to shape disease progression. Increasing evidence highlights the dual role of the urinary and gut microbiota in modulating bladder carcinogenesis through infection-driven inflammation and immune dysfunction. Chronic exposure to uropathogens and microbial imbalance disrupts epithelial integrity, promotes extracellular matrix degradation, and reprograms local immune signaling, collectively fostering a tumor-permissive niche. Concurrently, immunosenescence exacerbates microbial persistence and impairs antitumor immunity, reinforcing a pathogenic feedback loop between infection and immune decline. This review integrates current insights from microbiome research, tumor immunology, and microbial pathogenesis to delineate the mechanistic continuum linking infection, dysbiosis, and immune remodeling in BC. Finally, we discuss emerging microbiome-targeted and immunomodulatory strategies aimed at restoring microbial–immune equilibrium and improving therapeutic efficacy. Together, these perspectives provide a refined conceptual framework for understanding infection-driven oncogenesis and guiding precision interventions in BC.

Differentiating whether plant products are natural or artificial is of great importance in many practical fields, including forensic science, food safety, cosmetics, and fast-moving consumer goods. Information about the topographic distribution of compounds is an important criterion for answering this question. However, of equal importance is the likelihood that topographic spatial distribution information may provide important and valuable information for molecular mechanism study. In this study, we took mescaline, a substance with hallucinogenic properties in cacti of the species and , as an example to characterize the spatial distribution of mescaline in plants and flowers by liquid chromatograph-mass spectrometry-matrix-assisted laser desorption/ionization mass spectrometry imaging at the macroscopic, tissue structure, and even cellular levels. According to our results, the distribution of mescaline in natural plant was concentrated on the active meristems, epidermal tissues, and protruding parts of and , while artificially spiked products showed no such difference in their topographic spatial distribution. This difference in distribution pattern allowed us to distinguish between flowers that could synthesize mescaline on their own and those that had been artificially spiked with mescaline. The interesting topographic spatial distribution results, such as the overlap of the mescaline distribution map and micrographs of the vascular bundles, were consistent with the synthesis and transport theory of mescaline, indicating the potential for applying matrix-assisted laser desorption/ionization mass spectrometry imaging in botanical research.

Natural compounds in plants are often unevenly distributed, and determining the best sampling locations to obtain the most representative results is technically challenging. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can provide the basis for formulating sampling guideline. For a succulent plant sample, ensuring the authenticity and in situ nature of the spatial distribution analysis results during MSI analysis also needs to be thoroughly considered. In this study, we developed a well-established and reliable MALDI-MSI method based on preservation methods, slice conditions, auxiliary matrices, and MALDI parameters to detect and visualize the spatial distribution of mescaline in situ in Lophophora williamsii. The MALDI-MSI results were validated using liquid chromatography–tandem mass spectrometry. Low-temperature storage at −80°C and drying of “bookmarks” were the appropriate storage methods for succulent plant samples and their flower samples, and cutting into 40 μm thick sections at −20°C using gelatin as the embedding medium is the appropriate sectioning method. The use of DCTB (trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile) as an auxiliary matrix and a laser intensity of 45 are favourable MALDI parameter conditions for mescaline analysis. The region of interest semi-quantitative analysis revealed that mescaline is concentrated in the epidermal tissues of L. williamsii as well as in the meristematic tissues of the crown. The study findings not only help to provide a basis for determining the best sampling locations for mescaline in L. williamsii, but they also provide a reference for the optimization of storage and preparation conditions for raw plant organs before MALDI detection. Key Points An accurate in situ MSI method for fresh water-rich succulent plants was obtained based on multi-parameter comparative experiments. Spatial imaging analysis of mescaline in Lophophora williamsii was performed using the above method. Based on the above results and previous results, a sampling proposal for forensic medicine practice is tentatively proposed.

Background: Previous randomized studies have assessed the possibility of omission of chemotherapy in some hormone receptor (HR)-positive and HER2-negative (HR+/HER2-) breast cancers (BC) based on gene profiling test, e.g., Oncotype DX. The goal of this study was to evaluate if combination of six proliferation related biomarkers by immunohistochemistry (6-IHC) could be a cost-effective option in determining the necessity of adjuvant chemotherapy in HR+/HER2- BC. Methods: A retrospective analysis of HR+/HER2- BC patients was conducted in the First Affiliated Hospital of China Medical University from 2010 to 2016. The expression of 6 BC-related proliferation and invasion genes (Cathepsin L2, MMP11, CyclinB1, Aurora A, Survivin and Ki67) from Oncotype DX were analyzed through IHC (designated as 6-IHC). All the included patients were divided randomly at a 7:3 ratio into training and testing cohorts. The cutoff prognosis index (PI) of 6-IHC was determined by multivariate Cox risk regression analysis after calculating the PI of each patient in training cohort and confirmed in testing cohort. The patients were classified into “Low” and “High” risk groups based on the PI value. Kaplan-Meier (KM) method was used to analyze Disease-free survival (DFS) and overall survival (OS). 6-IHC score and other factors associated with survival benefit of adjuvant chemotherapy were compared with Ki67 index. Results: A total of 330 patients were included and divided into training cohort (n = 231) and validation cohort (n = 99). The receiver operating characteristic (ROC) curve analysis showed that the patients can be divided into 6-IHC score “High” and “Low” risk groups using the cut-off PI of 2.16. The 8-year DFS and OS were 54.6% and 69.2%, respectively in the 6-IHC score “High” risk group; 85.5% and 92.5%, respectively in the 6-IHC score “Low” risk group. The 8-year DFS and OS were 70.8% and 80.9%, respectively in the Ki67 “High” risk group, 77.7% and 87.6%, respectively in the Ki67 “Low” risk group. The KM curves showed that chemotherapy did not significantly improve the DFS in the 6-IHC score “Low” risk group (p = 0.830), but significantly improved the DFS in the 6-IHC score “High” risk group (P = 0.012). Conclusions: Combined 6-IHC score could be a reliable tool in predicting cancer-specific recurrences and survival in HR+/HER2- BC patients and identifying patients who could benefit from adjuvant chemotherapy regardless of the involvement of axillary lymph node (ALN).

Folliculogenesis is a complex biological process involving a central oocyte and its surrounding somatic cells. Three-dimensional chromatin architecture is an important transcription regulator; however, little is known about its dynamics and role in transcriptional regulation of granulosa cells during chicken folliculogenesis. We investigate the transcriptomic dynamics of chicken granulosa cells over ten follicular stages and assess the chromatin architecture dynamics and how it influences gene expression in granulosa cells at three key stages: the prehierarchical small white follicles, the first largest preovulatory follicles, and the postovulatory follicles. Our results demonstrate the consistency between the global reprogramming of chromatin architecture and the transcriptomic divergence during folliculogenesis, providing ample evidence for compartmentalization rearrangement, variable organization of topologically associating domains, and rewiring of the long-range interaction between promoter and enhancers. These results provide key insights into avian reproductive biology and provide a foundational dataset for the future in-depth functional characterization of granulosa cells. The domestic chicken Gallus gallus domesticus is a classic model for the study of folliculogenesis. Here the authors integrate multi-omics analyses characterizing the dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis.

The study of chromatin accessibility across tissues and developmental stages is essential for elucidating the transcriptional regulation of various phenotypes and biological processes. However, the chromatin accessibility profiles of multiple tissues in newborn pigs and across porcine liver development remain poorly investigated. Here, we used ATAC-seq and rRNA-depleted RNA-seq to profile open chromatin maps and transcriptional features of heart, kidney, liver, lung, skeletal muscle, and spleen in newborn pigs and porcine liver tissue in the suckling and adult stages, respectively. Specifically, by analyzing a union set of protein-coding genes (PCGs) and two types of transcripts (lncRNAs and TUCPs), we obtained a comprehensive annotation of consensus ATAC-seq peaks for each tissue and developmental stage. As expected, the PCGs with tissue-specific accessible promoters had active transcription and were relevant to tissue-specific functions. In addition, other non-coding tissue-specific peaks were involved in both physical activity and the morphogenesis of neonatal tissues. We also characterized stage-specific peaks and observed a close association between dynamic chromatin accessibility and hepatic function transition during liver postnatal development. Overall, this study expands our current understanding of epigenetic regulation in mammalian tissues and organ development, which can benefit both economic trait improvement and improve the biomedical usage of pigs.

Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock breeding. Despite ongoing attempts since the 1990s, no stably defined pig epiblast-derived stem cell line has been established. Here, guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day (E) 0 to E14, specifically, the tracing of pluripotency changes during epiblast development, we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts (pgEpiSCs). Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK, JAK/STAT3, and Activin/Nodal pathways, pgEpiSCs maintain their pluripotency transcriptome features, similar to those of E10 epiblast cells, and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers. Strikingly, ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in pgEpiSCs. In practice, we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live piglets. Our findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research, animal husbandry, and regenerative biomedicine.

Food contamination caused by food-spoilage bacteria and pathogenic bacteria seriously affects public health. Staphylococcus aureus is a typical foodborne pathogen which easily forms biofilm. Once biofilm is formed, it is difficult to remove. The use of nanotechnology for antibiofilm purposes is becoming more widespread because of its ability to increase the bioavailability and biosorption of many drugs. In this work, chitosan nanoparticles (CSNPs) were prepared by the ion–gel method with polyanionic sodium triphosphate (TPP). Cinnamaldehyde (CA) was loaded onto the CSNPs. The particle size, potential, morphology, encapsulation efficiency and in vitro release behavior of cinnamaldehyde–chitosan nanoparticles (CSNP-CAs) were studied, and the activity of CA against S. aureus biofilms was evaluated. The biofilm structure on the silicone surface was investigated by scanning electron microscopy (SEM). Confocal laser scanning microscopy (CLSM) was used to detect live/dead organisms within biofilms. The results showed that CSNP-CAs were dispersed in a circle with an average diameter of 298.1 nm and a zeta potential of +38.73 mV. The encapsulation efficiency of cinnamaldehyde (CA) reached 39.7%. In vitro release studies have shown that CA can be continuously released from the CSNPs. Compared with free drugs, CSNP-CAs have a higher efficacy in removing S. aureus biofilm, and the eradication rate of biofilm can reach 61%. The antibiofilm effects of CSNP-CAs are determined by their antibacterial properties. The minimum inhibitory concentration (MIC) of CA is 1.25 mg/mL; at this concentration the bacterial cell wall ruptures and the permeability of the cell membrane increases, which leads to leakage of the contents. At the same time, we verified that the MIC of CSNP-CAs is 2.5 mg/mL (drug concentration). The synergy between CA and CSNPs demonstrates the combinatorial application of a composite as an efficient novel therapeutic agent against antibiofilm. We can apply it in food preservation and other contexts, providing new ideas for food preservation.