Bioaccessibility and health risk assessment of hydrophobic organic pollutants in soils from four typical industrial contaminated sites in China.

There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27‒14.3 ng/g) and OPFRs (6.30‒310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.

Efficient chlorination reaction of Pt/RuO2/g-C3N4 under visible light irradiation for simultaneous removal of ammonia and bacteria from mariculture wastewater.

The removal of ammonia nitrogen (NH4+-N) and bacteria from aquaculture wastewater holds paramount ecological and production significance. In this study, Pt/RuO2/g-C3N4 photocatalysts were prepared by depositing Pt and RuO2 particles onto g-C3N4. The physicochemical properties of photocatalysts were explored by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-vis diffuse reflectance spectrometer (UV-vis DRS). The photocatalysts were then applied to the removal of both NH4+-N and bacteria from simulated mariculture wastewater. The results clarified that the removals of both NH4+-N and bacteria were in the sequence of g-C3N4 < RuO2/g-C3N4 < Pt/g-C3N4 < Pt/RuO2/g-C3N4. This magnificent photocatalytic ability of Pt/RuO2/g-C3N4 can be interpreted by the transfer of holes from g-C3N4 to RuO2 to facilitate the in situ generation of HClO from Cl- in wastewater, while Pt extracts photogenerated electrons for H2 formation to enhance the reaction. The removal of NH4+-N and disinfection effect were more pronounced in simulated seawater than in pure water. The removal efficiency of NH4+-N increases with an increase in pH of wastewater, while the bactericidal effect was more significant under a lower pH in a pH range of 6-9. In actual seawater aquaculture wastewater, Pt/RuO2/g-C3N4 still exhibits effective removal efficiency of NH4+-N and bactericidal performance under sunlight. This study provides an alternative avenue for removement of NH4+-N and bacteria from saline waters under sunlight.

The synthesis of 3D organic-inorganic hybrid heterojunctions of g-C3N4 nanoneedles@Ti3C2 MXene with superior photocatalytic H2 evolution.

3D organic-inorganic hybrid heterojunctions of 1D carbon nitride (g-C3N4) nanoneedles anchoring on 2D Ti3C2 MXene nanosheets have been constructed via a green molten salt treatment. The Ti3C2 MXene nanosheets and molten salt treatment guide the formation of ordered nanoneedle-like g-C3N4. Both the formed heterojunctions and the nanoneedle-like structures contribute charge separation and transfer for superior photocatalytic H2 evolution.

Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.

Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.

3-D bioprinted human-derived skin organoids accelerate full-thickness skin defects repair.

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

Fluid biomarkers in the context of amyloid-targeting disease-modifying treatments in Alzheimer's disease.

Clinical management and therapeutics development for Alzheimer's disease (AD) have entered a new era, with recent approvals of monoclonal antibody therapies targeting the underlying pathophysiology of the disease and modifying its trajectory. Imaging and fluid biomarkers are becoming increasingly important in the clinical development of AD therapeutics. This review focuses on the evidence of fluid biomarkers from recent amyloid-ß-targeting clinical trials, summarizing biomarker data across 12 trials. It further proposes a simple framework to put biomarker guidance in the context of amyloid-pathway-targeted disease modification, delineates factors that impact biomarker data in clinical trials, and highlights knowledge gaps and future directions. Increased knowledge and data on biomarkers in the context of disease progression and disease modification will help to better design future AD trials and guide the clinical management of patients on AD-modifying therapies, bringing us closer to the implementation of precision medicine in AD.

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Spatial variability of throughfall (i.e. the non-uniform characteristics of throughfall at different canopy positions) and its temporal persistence (i.e. time stability) are related to the quantity and efficiency of soil moisture replenishment, and affect plant competition and community succession dynamics by affecting resource availability. We carried out a meta-analysis with 554 papers (from 2000 to 2022) retrieved from Web of Science and China National Knowledge Infrastructure (CNKI) based on keyword search, quantified and compared the amount, spatial heterogeneity, and temporal stability characteristics of penetrating rain in different climate zones and plant functional types. Our results that throughfall proportion was lower in arid regions (72.0%±13.6%) than humid (75.1%±9.3%) and semi-humid areas (79.9%±10.4%). Cold climates had lower values (74.1%±14.6%) than temperate (74.2%±7.5%) and tropical climates (80.9%±14.6%). Shrubs (68.9%±14.9%) generally had lower throughfall proportion than trees (76.7%±9.1%). Broad-leaved trees (75.2%±11.1%) and conifers (75.1%±9.9%) showed similar throughfall proportions, as did evergreen (76.7%±10.0%) and deciduous species (74.7%±11.9%). Additionally, spatial variability (coefficient of variation) did not significantly differ across rainfall zones, temperature zones, or vegetation types. The spatial distribution of throughfall was relatively stable. Canopy structure was the dominant factor affecting temporal stability of throughfall. However, there was a lack of comparison between typical geographic units (i.e. spatial units with basically consistent geographical environmental conditions) at various temporal scales. Future research should expand upwards to the summary of global spatial scale rules and downwards to the analysis of process based temporal scale mechanisms, to depict the dynamic distribution of penetrating rain and unify observation standards to enhance comparability of different studies, in order to efficiently promote research on canopy penetrating rain and provide ecological and hydrological basis for protecting nature, managing artificial activities, and restoring degraded ecosystems.

Effects of microencapsulated plant essential oils on growth performance, immunity, and intestinal health of weaned Tibetan piglets.

Introduction: Plant essential oils (PEOs) have received significant attention in animal production due to their diverse beneficial properties and hold potential to alleviate weaning stress. However, PEOs effectiveness is often compromised by volatility and degradation. Microencapsulation can enhance the stability and control release rate of essential oils. Whether different microencapsulation techniques affect the effectiveness remain unknown. This study aimed to investigate the effects of PEOs coated by different microencapsulation techniques on growth performance, immunity, and intestinal health of weaned Tibetan piglets. Methods: A total of 120 Tibetan piglets, aged 30 days, were randomly divided into five groups with four replicates, each containing six piglets. The experimental period lasted for 32 days. The groups were fed different diets: a basal diet without antibiotics (NC), a basal diet supplemented with 10 mg/kg tylosin and 50 mg/kg colistin sulfate (PC), 300 mg/kg solidified PEO particles (SPEO), 300 mg/kg cold spray-coated PEO (CSPEO), or 300 mg/kg hot spray-coated PEO (HSPEO). Results: The results showed that supplementation with SPEO, CSPEO, or HSPEO led to a notable decrease in diarrhea incidence and feed to gain ratio, as well as duodenum lipopolysaccharide content, while simultaneously increase in average daily gain, interleukin-10 (IL-10) levels and the abundance of ileum Bifidobacterium compared with the NC group (p < 0.05). Supplementation with SPEO, CSPEO, or HSPEO significantly elevated serum immunoglobulin G (IgG) levels and concurrently reduced serum lipopolysaccharide and interferon γ levels compared with the NC and PC groups (p < 0.05). Serum insulin-like growth factor 1 (IGF-1) levels in the SPEO and HSPEO groups significantly increased compared with the NC group (p < 0.05). Additionally, CSPEO and HSPEO significantly reduced jejunum pH value (p < 0.05) compared with the NC and PC groups (p<0.05). Additionally, Supplementation with HSPEO significantly elevated levels of serum immunoglobulin M (IgM) and interleukin-4 (IL-4), abundance of ileum Lactobacillus, along with decreased serum interleukin-1 beta (IL-1ß) levels compared with both the NC and PC groups. Discussion: Our findings suggest that different microencapsulation techniques affect the effectiveness. Dietary supplemented with PEOs, especially HSPEO, increased growth performance, improved immune function, and optimized gut microbiota composition of weaned piglets, making it a promising feed additive in piglet production.

Long-Term Care Residents' Perceptions of Integrated Care From Physio-Psycho-Social Perspectives: A Qualitative Inquiry.

In response to the aging population, an integrated care policy has been put forward and implemented in China. The key aspect of this policy is the reform of services within long-term care facilities, representing a significant shift and innovation. This study aims to explore the perceptions and experiences of integrated care among older residents living in long-term care facilities. A descriptive qualitative design was applied in our study. Utilizing a purposive sampling method, 18 older adults from 5 long-term care institutions in Shanghai, China were selected. Data were collected through semi-structured in-depth interviews from October 2022 to April 2023, continuing until data saturation was reached. Directed content analysis was applied to analyze the interview data, guided by the Fundamentals of Care (FoC) Framework. Five themes and 11 subthemes were identified, including (1) Policy level: positive attitude and negative feelings. (2) Physiological level: satisfied basic daily life, primary medical services accessibility and chronic care management enhancement needed. (3) Psychological level: need for psychological support and need for self-perception recognition. (4) Relationship level: enhancement of humanistic care and need for a family atmosphere. (5) Social level: interpersonal communication constrained by the times and inadequate social engagement. Strengthening the awareness and participation of older people in the integrated care policy, and fully meeting the diverse needs including advanced medical care, chronic disease management, personalized life care, psychological support, humanistic care and social engagement will contribute to the improvement of the policy, so as to better adapt the demographic shift.

Sodium Houttuyniae attenuates ferroptosis by regulating TRAF6-c-Myc signaling pathways in lipopolysaccharide-induced acute lung injury (ALI).

The impact of Sodium Houttuyniae (SH) on lipopolysaccharide (LPS)-induced ALI has been investigated extensively. However, it remains ambiguous whether ferroptosis participates in this process. This study aimed to find out the impacts and probable mechanisms of SH on LPS-induced ferroptosis. A rat ALI model and type II alveolar epithelial (ATII) cell injury model were treated with LPS. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and Giemsa staining were executed to ascertain the effects of SH on LPS-induced ALI. Moreover, Transmission electron microscopy, Cell Counting Kit-8 (CCK8), ferrous iron colorimetric assay kit, Immunohistochemistry, Immunofluorescence, Reactive oxygen species assay kit, western blotting (Wb), and qRT-PCR examined the impacts of SH on LPS-induced ferroptosis and ferroptosis-related pathways. Theresults found that by using SH treatment, there was a remarkable attenuation of ALI by suppressing LPS-induced ferroptosis. Ferroptosis was demonstrated by a decline in the levels of glutathione peroxidase 4 (GPX4), FTH1, and glutathione (GSH) and a surge in the accumulation of malondialdehyde (MDA), reactive oxygen species (ROS), NOX1, NCOA4, and Fe2+, and disruption of mitochondrial structure, which were reversed by SH treatment. SH suppressed ferroptosis by regulating TRAF6-c-Myc in ALI rats and rat ATII cells. The results suggested that SH treatment attenuated LPS-induced ALI by repressing ferroptosis, and the mode of action can be linked to regulating the TRAF6-c-Myc signaling pathway in vivo and in vitro.

Dynamic Changes of Active Components and Volatile Organic Compounds in Rosa roxburghii Fruit during the Process of Maturity.

Rosa roxburghii (R. roxburghii), native to the southwest provinces of China, is a fruit crop of important economic value in Guizhou Province. However, the changes in fruit quality and flavor during R. roxburghii fruit ripening have remained unknown. Here, this study investigated the changes of seven active components and volatile organic compounds (VOCs) during the ripening of the R. roxburghii fruit at five different ripening stages including 45, 65, 75, 90, and 105 days after anthesis. The results indicated that during the ripening process, the levels of total acid, vitamin C, and soluble sugar significantly increased (p < 0.05), while the levels of total flavonoids, superoxide dismutase (SOD), and soluble tannin significantly decreased (p < 0.05). Additionally, the content of total phenol exhibited a trend of first decreasing significantly and then increasing significantly (p < 0.05). A total of 145 VOCs were detected by HS-SPME-GC-MS at five mature stages, primarily consisting of aldehydes, alcohols, esters, and alkenes. As R. roxburghii matured, both the diversity and total quantity of VOCs in the fruit increased, with a notable rise in the contents of acids, ketones, and alkenes. By calculating the ROAV values of these VOCs, 53 key substances were identified, which included aromas such as fruit, citrus, green, caramel, grass, flower, sweet, soap, wood, and fat notes. The aromas of citrus, caramel, sweet, and wood were predominantly concentrated in the later stages of R. roxburghii fruit ripening. Cluster heatmap analysis revealed distinct distribution patterns of VOCs across five different maturity stages, serving as characteristic chemical fingerprints for each stage. Notably, stages IV and V were primarily characterized by a dominance of alkenes. OPLS-DA analysis categorized the ripening process of R. roxburghii fruit into three segments: the first segment encompassed the initial three stages (I, II, and III), the second segment corresponded to the fourth stage (IV), and the third segment pertained to the fifth stage (V). Following the variable importance in projection (VIP) > 1 criterion, a total of 30 key differential VOCs were identified across the five stages, predominantly comprising ester compounds, which significantly influenced the aroma profiles of R. roxburghii fruit. By integrating the VIP > 1 and ROAV > 1 criteria, 21 differential VOCs were further identified as key contributors to the aroma changes in R. roxburghii fruit during the ripening process. This study provided data on the changes in quality and aroma of R. roxburghii fruit during ripening and laid the foundation for the investigation of the mechanism of compound accumulation during ripening.

A versatile and efficient method for detecting tRNA-derived fragments.

Recently, it has been discovered surprisingly that tRNA can be cleaved into specific small fragments under certain conditions. Most importantly, these tRNA-derived fragments (tRFs) participate in the regulation of gene expression, playing pivotal roles in various physiological and pathological processes and thus attracting widespread attention. Detecting tRF expression in tissues and cells often involves using tRF-specific stem-loop primers for reverse transcription. However, the high specificity offered by this method limits it to transcribing only one specific tRF sequence per reaction, necessitating separate reverse transcription and qPCR steps for multiple tRFs, leading to substantially increased time and resource consumption. This becomes especially challenging in precious samples with limited RNA availability. To address these issues, there is an urgent need for a universal and cost-effective tRF identification method. This study introduces a versatile tRF detection approach based on the uniform polyadenylation of all tRFs, allowing reverse transcription with a universal oligo(dT) primer. This method enables simultaneous reverse transcription of all target tRFs in one reaction, greatly facilitating subsequent qPCR analysis. Furthermore, it demonstrates exceptional sensitivity and specificity, offering significant value in tRF-related research.

Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer's disease.

The Alzheimer's disease (AD)-affected brain purges K with concurrently increasing serum K, suggesting brain-blood K transferal. Here, natural stable K isotope ratios-δ41K-of human serum samples were characterized in an AD biomarker pilot study (plus two paired Li-heparin and potassium ethylenediaminetetraacetic acid [K-EDTA] plasma samples). AD serum was found to have a significantly lower mean δ41K relative to controls. To mechanistically explore this change, novel ab initio calculations (density functional theory) of relative K isotope compositions between hydrated K+ and organically bound K were performed, identifying hydrated K+ as isotopically light (lower δ41K) compared to organically bound K. Taken together with literature, serum δ41K and density functional theory results are consistent with efflux of hydrated K+ from the brain to the bloodstream, manifesting a measurable decrease in serum δ41K. These data introduce serum δ41K for further investigation as a minimally invasive AD biomarker, with cost, scalability, and stability advantages over current techniques.

Advanced glycation end products mediate biomineralization disorder in diabetic bone disease.

Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

Oral delivery of sodium alginate/chitosan bilayer microgels loaded with Lactobacillus rhamnosus GG for targeted therapy of ulcerative colitis.

Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2 % in simulated gastric juice (pH 1.2) for 2 h, whereas that of encapsulated LGG decreased by 18.5 %. In the DSS-induced inflammatory model, LGG-loaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.

Age-associated clonal B cells drive B cell lymphoma in mice.

Although cancer is an age-related disease, how the processes of aging contribute to cancer progression is not well understood. In this study, we uncovered how mouse B cell lymphoma develops as a consequence of a naturally aged system. We show here that this malignancy is associated with an age-associated clonal B cell (ACBC) population that likely originates from age-associated B cells. Driven by c-Myc activation, promoter hypermethylation and somatic mutations, IgM+ ACBCs clonally expand independently of germinal centers and show increased biological age. ACBCs become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates pre-malignant changes in B cells during aging. Although the etiology of mouse and human B cell lymphomas is considered distinct, epigenetic changes in transformed mouse B cells are enriched for changes observed in human B cell lymphomas. Together, our findings characterize the spontaneous progression of cancer during aging through both cell-intrinsic and microenvironmental changes and suggest interventions for its prevention.

Prevalence and antimicrobial susceptibility pattern of Mycobacterium abscessus complex isolates in Chongqing, Southwest China.

Objectives: To investigate the prevalence of Mycobacterium abscessus complex (MABC), drug resistance characteristics, and the relationship between clarithromycin (CLA) susceptibility and MABC genotype in Chongqing, China. Methods: A total of 434 NTM patient isolates were collected between October 2018 and October 2019. Isolates confirmed to be non-tuberculous mycobacteria (NTM) were tested for minimal inhibitory concentrations of antimicrobial agents. In addition, rrl and erm(41) gene sequences were used to analyze the acquired macrolide resistance and inducible macrolide resistance. Results: Overall, 17 different NTM species were detected, of which M. abscessus (22.6 %, 91/403) was most prevalent. Amikacin, CLA, azithromycin and cefoxitin exhibited potent activities against MABC organisms, but no significant differences were observed in drug resistance rates between M. abscessus and M. massiliense (P > 0.05). On day 3 of culture, the acquired resistance rate against CLA was 7.4 % (9/121). Of 41 MABC isolates with inducible CLA resistant, 95.1 % (39/41) isolates belonged to the erm(41) T28 sequevar, while the remaining 4.9 % (2/41) possessed the M. massiliense genotype. All erm(41) C28 sequevar isolates were sensitive to CLA on day3 and day 14 of culture. Meanwhile, of the 5 erm(41) T28 isolates with acquired resistance, all possessed rrl 2058/2059 mutations, including 3 isolates with A2058C mutation and 2 isolates with A2059G mutation. While 2 of the 4 M. massiliense isolates with acquired resistance possessed the A2059G mutation, and one isolate possessed the A2058G mutation. Conclusion: Erm(41) and rrl gene could serve as useful markers for predicting macrolide susceptibility of MABC complex isolates.

Canagliflozin attenuates post-resuscitation myocardial dysfunction in diabetic rats by inhibiting autophagy through the PI3K/Akt/mTOR pathway.

This study investigated the effects of canagliflozin on myocardial dysfunction after cardiac arrest and cardiopulmonary resuscitation in diabetic rats and the underlying mechanisms. Male rats with type 2 diabetes mellitus (T2DM) were subjected to a modified epicardial fibrillation model. Pretreatment with canagliflozin (10 mg/kg/day) for four weeks improved ATP levels, post-resuscitation ejection fraction, acidosis, and hemodynamics. Canagliflozin also reduced myocardial edema, mitochondrial damage and, post-resuscitation autophagy levels. In vitro analyses showed that canagliflozin significantly reduced reactive oxygen species and preserved mitochondrial membrane potential. Using the PI3K/Akt pathway inhibitor Ly294002, canagliflozin was shown to attenuate hyperautophagy and cardiac injury induced by high glucose and hypoxia-reoxygenation through activation of the PI3K/Akt/mTOR pathway. This study highlights the therapeutic potential of canagliflozin in post-resuscitation myocardial dysfunction in diabetes, providing new insights for clinical treatment and experimental research.

N6-methyladenosine RNA modification regulates photoperiod sensitivity in cotton.

The methylation of N6-methyladenosine (m6A) involves writers, erasers, and readers, acting synergistically in posttranscriptional regulation. These processes influence various biological processes, including plant floral transition. However, the specific role of m6A modifications in photoperiod sensitivity in cotton (Gossypium hirsutum) remains obscure. To elucidate this, in this study, we conducted transcriptome-wide m6A sequencing during critical flowering transition stages in the photoperiod-sensitive wild G. hirsutum var. yucatanense (yucatanense) and the photoperiod-insensitive cultivated cotton G. hirsutum acc. TM-1 (TM-1). Our results revealed significant variations in m6A methylation of 2 cotton varieties, with yucatanense exhibiting elevated m6A modification levels compared with TM-1 under long-day conditions. Notably, distinct m6A peaks between TM-1 and yucatanense correlated significantly with photoperiod sensitivity. Moreover, our study highlighted the role of the demethylase G. hirsutum ALKB homolog 5 (GhALKBH5) in modulating m6A modification levels. Silencing GhALKBH5 led to a decreased mRNA level of key photoperiodic flowering genes (GhADO3, GhAGL24, and GhFT1), resulting in delayed bud emergence and flowering. Reverse transcription quantitative PCR analyses confirmed that silencing GhADO3 and GhAGL24 significantly downregulated the expression of the floral integrator GhFT1. Collectively, our findings unveiled a transcriptional regulatory mechanism in which GhALKBH5-mediated m6A demethylation of crucial photoperiodic flowering transcripts modulated photoperiod sensitivity in cotton.