Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures.

JOURNAL/nrgr/04.03/01300535-202501000-00034/figure1/v/2024-05-14T021156Z/r/image-tiff Certain amino acids changes in the human Na+/K+-ATPase pump, ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1), cause Charcot-Marie-Tooth disease type 2 (CMT2) disease and refractory seizures. To develop in vivo models to study the role of Na+/K+-ATPase in these diseases, we modified the Drosophila gene homolog, Atpα, to mimic the human ATP1A1 gene mutations that cause CMT2. Mutations located within the helical linker region of human ATP1A1 (I592T, A597T, P600T, and D601F) were simultaneously introduced into endogenous DrosophilaAtpα by CRISPR/Cas9-mediated genome editing, generating the AtpαTTTF model. In addition, the same strategy was used to generate the corresponding single point mutations in flies (AtpαI571T, AtpαA576T, AtpαP579T, and AtpαD580F). Moreover, a deletion mutation (Atpαmut) that causes premature termination of translation was generated as a positive control. Of these alleles, we found two that could be maintained as homozygotes (AtpαI571T and AtpαP579T). Three alleles (AtpαA576T, AtpαP579 and AtpαD580F) can form heterozygotes with the Atpαmut allele. We found that the Atpα allele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila. Flies heterozygous for AtpαTTTF mutations have motor performance defects, a reduced lifespan, seizures, and an abnormal neuronal morphology. These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

The origins of dual-peak emission and anomalous exciton decay in 2D Sn-based perovskites.

Two-dimensional (2D) Sn-based perovskites exhibit significant potential in diverse optoelectronic applications, such as on-chip lasers and photodetectors. Yet, the underlying mechanism behind the frequently observed dual-peak emission in 2D Sn-based perovskites remains a subject of intense debate, and there is a lack of research on the carrier dynamics in these materials. In this study, we investigate these issues in a representative 2D Sn-based perovskite, namely, PEA2SnI4, through temperature-, excitation intensity-, angle-, and time-dependent photoluminescence studies. The results indicate that the high- and low-energy peaks originate from in-face and out-of-face dipole transitions, respectively. In addition, we observe an anomalous increase in the non-radiative recombination rate as temperature decreases. After ruling out enhanced electron-phonon coupling and Auger recombination as potential causes of the anomalous carrier dynamics, we propose that the significantly increased exciton binding energy (Eb) plays a decisive role. The increased Eb arises from enhanced electronic localization, a consequence of weakened lattice distortion at low temperatures, as confirmed by first-principles calculations and temperature-dependent x-ray diffraction measurements. These findings offer valuable insights into the electronic processes in the unique 2D Sn-based perovskites.

Deep migration learning-based recognition of diseases and insect pests in Yunnan tea under complex environments.

BACKGROUND: The occurrence, development, and outbreak of tea diseases and pests pose a significant challenge to the quality and yield of tea, necessitating prompt identification and control measures. Given the vast array of tea diseases and pests, coupled with the intricacies of the tea planting environment, accurate and rapid diagnosis remains elusive. In addressing this issue, the present study investigates the utilization of transfer learning convolution neural networks for the identification of tea diseases and pests. Our objective is to facilitate the accurate and expeditious detection of diseases and pests affecting the Yunnan Big leaf kind of tea within its complex ecological niche. RESULTS: Initially, we gathered 1878 image data encompassing 10 prevalent types of tea diseases and pests from complex environments within tea plantations, compiling a comprehensive dataset. Additionally, we employed data augmentation techniques to enrich the sample diversity. Leveraging the ImageNet pre-trained model, we conducted a comprehensive evaluation and identified the Xception architecture as the most effective model. Notably, the integration of an attention mechanism within the Xeption model did not yield improvements in recognition performance. Subsequently, through transfer learning and the freezing core strategy, we achieved a test accuracy rate of 98.58% and a verification accuracy rate of 98.2310%. CONCLUSIONS: These outcomes signify a significant stride towards accurate and timely detection, holding promise for enhancing the sustainability and productivity of Yunnan tea. Our findings provide a theoretical foundation and technical guidance for the development of online detection technologies for tea diseases and pests in Yunnan.

Coloration in Equine: Overview of Candidate Genes Associated with Coat Color Phenotypes.

Variation in coat color among equids has attracted significant interest in genetics and breeding research. The range of colors is primarily determined by the type, concentration, and distribution of melanin pigments, with the balance between eumelanin and pheomelanin influenced by numerous genetic factors. Advances in genomic and sequencing technologies have enabled the identification of several candidate genes that influence coat color, thereby clarifying the genetic basis of these diverse phenotypes. In this review, we concisely categorize coat coloration in horses and donkeys, focusing on the biosynthesis and types of melanin involved in pigmentation. Moreover, we highlight the regulatory roles of some key candidate genes, such as MC1R, TYR, MITF, ASIP, and KIT, in coat color variation. Moreover, the review explores how coat color relates to selective breeding and specific equine diseases, offering valuable insights for developing breeding strategies that enhance both the esthetic and health aspects of equine species.

Booster vaccines dose reduced mortality in hospitalized COVID-19 patients requiring oxygen supplementation: Evidence from the Beijing Omicron outbreak.

To assess the impact of vaccines on clinical outcomes among hospitalized COVID-19-infected patients requiring oxygen supplementation during the Beijing Omicron outbreak. We conducted a retrospective cohort study at Beijing Chaoyang Hospital, Capital Medical University, from November 15, 2022, to March 31, 2023. Vaccination statuses were categorized into 3 doses, 2 doses, and unvaccinated (0 dose). The primary outcome was 28-day all-cause mortality. Secondary outcomes included poor outcomes, intensive care unit admission, cardiovascular thromboembolism events, and hospital readmission. Among the included patients, 117 were 2 doses, 285 received booster doses, and 503 were unvaccinated. After propensity score inverse probability weighting, the 3 doses group showed a significantly lower 28-day all-cause mortality compared to the unvaccinated group (inverse probability of treatment weighting-adjusted HR: 0.64, 95% CI: 0.50-0.81). No significant difference was observed in all-cause mortality between the 2 doses and unvaccinated groups. No significant differences were observed in secondary outcome analyses when comparing the 3 doses or 2 doses group to the unvaccinated group. Subgroup analysis revealed significant benefits of booster vaccination in patients with shorter symptom duration, lower Charlson Comorbidity Index, and without immunosuppression status. Our study highlights the significant reduction in all-cause mortality among hospitalized Omicron-infected patients who received a third dose vaccine. These findings underscore the importance of prioritizing booster vaccinations, especially among the elderly. Further research is warranted to confirm and extend these observations.

Micro- and Nanoengineered Metal Additively Manufactured Surfaces for Enhanced Anti-Frosting Applications.

The greater geometrical design freedom offered by additive manufacturing (AM) as compared to the conventional manufacturing method has attracted increasing interest in AM to develop innovative and complex designs for enhanced performance. However, the difference in material composition and surface properties from conventional alloys has made surface micro-/nanostructuring of AM metals challenging. Frost accretion is a safety hazard in numerous engineering applications. To expand the application of AM, this study experimentally investigates the antifrosting performance of superhydrophobic and slippery lubricant-infused porous surfaces (SLIPSs) generated on AM alloy, AlSi10Mg. By strategically utilizing the subgrain structure in the metallography of the AM alloy, the functionalized superhydrophobic AM surface featuring hierarchical structures was shown to greatly reduce frost formation as compared to functionalized single-tier structured surfaces, hierarchical structures formed on conventional aluminum alloy surfaces, and SLIPSs. Optical observation of frost propagation demonstrated that the mechanism of frost delay is governed by the inhibition of spontaneous droplet freezing through exceptional Cassie state stability during condensation frosting. The Cassie stability results from the unique AM structure morphology, which creates a higher structural energy barrier to prevent condensate from infiltrating the cavities. This phenomenon also enables the formation of a high surface-to-droplet thermal resistance, which eliminates spontaneous droplet freezing down to a -15 °C surface temperature. Our work demonstrates a scalable structuring method for AM metals, which can result in delayed frost formation, and it also provides guidelines for the development of engineered surfaces requiring the antifrosting function for several industries.

Coronary artery wall contrast enhancement imaging impact on disease activity assessment in IgG4-RD: a direct marker of coronary involvement.

BACKGROUND: Coronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment. METHODS: A total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0 T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis. RESULTS: Coronary wall CE was observed in 29 (94 %) IgG4-RD patients and 22 (76 %) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0-6.6] v. 1.7 [1.5-2.6] v. 0.3 [0.3-0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r = 0.55, P = 0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6 v. 16 ± 6, P < 0.001). CONCLUSIONS: Visualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation.

Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is an aggressive form of skin cancer with limited treatment options for advanced stages. Prognostic markers that accurately predict patients' outcomes and guide therapeutic strategies are crucial for improving melanoma management. SETD2 (SET Domain-Containing Protein 2), a histone methyltransferase involved in chromatin remodeling and gene regulation, has recently emerged as a tumor suppressor. Its dysfunction is involved in oncogenesis in some cancers, but little is known about its functions in progression and therapeutic response of melanoma. METHODS: RNA-seq and clinical data from public database were used to evaluate the survival analysis, gene set enrichment, IC50 of therapeutics and immunotherapy response. SETD2 knock-out A375 cell line (A375SETD2ko) was developed by Crispr/cas9 and CCK-8 analysis and nude mice used to evaluate the proliferation and invasion of melanoma cells in vitro and in vivo, while Western blotting tested the MMR-related protein. RESULTS: SETD2 was commonly down-regulated in melanoma samples which demonstrated an unfavorable survival. Cells without SETD2 expression tend to have a more progressive and invasive behavior, with resistance to chemotherapy. However, they are more sensitive to tyrosine kinase inhibitors (TKIs). They also exhibit inflamed features with lower TIDE (Tumor Immune Dysfunction and Exclusion) score and higher tumor mutation burden (TMB), showing that these patients may benefit from immunotherapy. CONCLUSIONS: This study revealed that SETD2 dysfunction in melanoma implied a poor prognosis and chemotherapy resistance, but highly sensitive to TKIs and immunotherapy, highlighting the prognostic and therapeutic value of SETD2 in cutaneous melanoma.

Lanthanide MOF-based luminescent sensor arrays for the detection of castration-resistant prostate cancer curing drugs and biomarkers.

In recent years, castration-resistant prostate cancer (CRPC) has profoundly impacted the lives of many men, and early diagnosis of medication and illness is crucial. Therefore, a highly efficient detection method for CRPC biomarkers and curing drugs is required. However, the complex and diverse structures of CRPC drugs pose significant challenges for their detection and differentiation. Lanthanide metal-organic frameworks (Ln-MOFs) show great potential for sensing applications due to their intense and characteristic luminescence. In this work, a series of new bimetallic Ln-MOFs (EuxTb1-x-MOF) based luminescent sensor arrays have been developed to identify CRPC drugs, including in mixtures, via principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods. These Ln-MOFs are built with a highly conjugated H2L linker (H2L = 5-(4-(triazole-1-yl)phenyl)isophthalic acid) and exhibit robust strong luminescence emissions (mainly located at 543 and 614 nm) and high energy transfer efficiencies. More specifically, Eu0.096Tb0.904-MOF (MOF 3) has demonstrated good sensing performances for CRPC curing drugs in real human serum samples. Furthermore, the curing drug hydroxyflutamide has been combined with MOF 3, to construct a robust composite sensing platform MOF 3@hydroxyflutamide for highly efficient detection of CRPC biomarkers such as the androgen receptor (AR) and prostate-specific antigen (PSA). Finally, luminescence lifetime measurements, zeta potential measurements, and density functional theory (DFT) calculations were performed to gain insights into the sensing mechanism.

Genome-wide analysis of UDP-glycosyltransferases family and identification of UGT genes involved in drought stress of Platycodon grandiflorus.

Introduction: The uridine diphosphate (UDP)-glycosyltransferase (UGT) family is the largest glycosyltransferase family, which is involved in the biosynthesis of natural plant products and response to abiotic stress. UGT has been studied in many medicinal plants, but there are few reports on Platycodon grandiflorus. This study is devoted to genome-wide analysis of UGT family and identification of UGT genes involved in drought stress of Platycodon grandiflorus (PgUGTs). Methods: The genome data of Platycodon grandiflorus was used for genome-wide identification of PgUGTs, online website and bioinformatics analysis software was used to conduct bioinformatics analysis of PgUGT genes and the genes highly responsive to drought stress were screened out by qRT-PCR, these genes were cloned and conducted bioinformatics analysis. Results: A total of 75 PgUGT genes were identified in P.grandiflorus genome and clustered into 14 subgroups. The PgUGTs were distributed on nine chromosomes, containing multiple cis-acting elements and 22 pairs of duplicate genes were identified. Protein-protein interaction analysis was performed to predict the interaction between PgUGT proteins. Additionally, six genes were upregulated after 3d under drought stress and three genes (PGrchr09G0563, PGrchr06G0523, PGrchr06G1266) responded significantly to drought stress, as confirmed by qRT-PCR. This was especially true for PGrchr06G1266, the expression of which increased 16.21-fold after 3d of treatment. We cloned and conducted bioinformatics analysis of three candidate genes, both of which contained conserved motifs and several cis-acting elements related to stress response, PGrchr06G1266 contained the most elements. Discussion: PgGT1 was confirmed to catalyze the C-3 position of platycodin D and only eight amino acids showed differences between gene PGr008G1527 and PgGT1, which means PGr008G1527 may be able to catalyze the C-3 position of platycodin D in the same manner as PgGT1. Seven genes were highly expressed in the roots, stems, and leaves, these genes may play important roles in the development of the roots, stems, and leaves of P. grandiflorus. Three genes were highly responsive to drought stress, among which the expression of PGrchr06G1266 was increased 16.21-fold after 3d of drought stress treatment, indicating that PGrchr06G1266 plays an important role in drought stress tolerance. To summarize, this study laied the foundation to better understand the molecular bases of responses to drought stress and the biosynthesis of platycodin.

Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency.

Liquid Chromatography-Mass Spectrometry-Based Metabolomics Reveals Dynamic Metabolite Changes during Early Postmortem Aging of Donkey Meat.

BACKGROUND: Metabolic changes in donkey meat during the early postmortem period have not been previously reported. METHODS: The LC-MS-based metabolomics technique was conducted to understand the metabolic profiles and identify the key metabolites of donkey meat in the first 48 h postmortem. RESULTS: The pH values showed a decreasing trend followed by an increasing trend. Shear force was the lowest at 4 h and the highest at 24 h (p < 0.05). For the metabolome, some candidate biomarker metabolites were identified, such as adenine, inosine, n-acetylhistidine, citric acid, isocitrate, and malic acid. Predominant metabolic pathways, such as citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism, and purine metabolism, were affected by aging time. Overabundant n-acetylhistidine was identified in LT, declined at 12 h postmortem aging, and then increased. This may explain the significantly lower pH at 12 h postmortem. Adenine was higher at 4 h postmortem, then declined. Decreased ADP may indicate a fast consumption of ATP and subsequent purine metabolism in donkey meat. CONCLUSIONS: The results of this study provided new insights into early postmortem aging of donkey meat quality.

Clinical characteristics and prognostic analysis of metachronous bilateral breast carcinoma: a retrospective study based on propensity score matching.

BACKGROUND: To investigate clinical characteristics, treatment, outcomes, and prognostic risk factors of metachronous bilateral breast carcinoma (MBBC) and provide a theoretical basis for clinical management of MBBC. METHODS: This was a retrospective study. From January 1, 2010 to March 31, 2022, a total of 23,010 patients with breast cancer underwent surgical treatment at the Breast Center of the Fourth Hospital of Hebei Medical University, including 386 patients with MBBC. Propensity score matching (PSM) was performed on MBBC patients and unilateral breast cancer (UBC) patients in a 1:1 ratio, and 210 UBC patients and 210 MBBC patients were finally matched. Clinical medical records of all patients were collected, including age of onset, family history of breast cancer, tumor size, lymph node status, TNM stage, mode of surgery, menstruation, pathological type, immunohistochemical (IHC) typing, treatment, disease-free survival (DFS), and overall survival (OS). RESULTS: The result showed that age of onset of the second primary cancer (SPC) was significantly older than that of the first primary cancer (FPC) (P = 0.024). Baseline data from MPPC patients showed that the tumor size of FPC was significantly larger than that of SPC (P = 0.043), and the proportion of PR ( +) in FPC is significantly higher than that in SPC (P = 0.045). Among MBBC patients with FPC for estrogen receptor (ER) or progesterone receptor (PR) ( +) and Her-2 (-), clinical characteristics and treatment results showed that the proportion of PR ( +) in the drug-resistant group was significantly lower than that in the non-drug-resistant group. The 2-year OS rate of SPC in the drug-resistant group was significantly shorter than those of the non-drug-resistant group (78.9% vs 100%, P < 0.05). The result of PSM-based comparison between MBBC patients and UBC patients showed significantly lower proportion of MBBC patients with SPC received chemotherapy compared to UBC patients (P = 0.026), and there was no significant difference in OS and DFS between SPC course of MBBC patients and UBC patients (P > 0.05). The univariate analysis showed that high TNM stage was a risk factor for death and disease progression in MBBC patients, with the risk of death in stage III MBBC patients being about 5 times higher than that in stage I MBBC patients (HR = 4.97, 95%CI = 1.42-17.31, P = 0.012), and the risk of disease recurrence being about 3.5 times higher than that in stage I MBBC patients (HR = 3.55, 95%CI = 1.07-11.81, P = 0.039). CONCLUSION: In summary, this study presented clinical characteristics, treatment options, and outcomes of MBBC patients and patients with MBBC who were resistant to endocrine therapy have a worse SPC survival prognosis. The course of SPC in MBBC patients was similar to that of UBC in terms of prognosis and survival, which suggested that SPC can be treated according to UBC treatment regimen. High TNM stage was a prognostic risk factor for SPC patients.

Impact of the Alberta Stroke Program CT Score subregions on long-term functional outcomes in acute ischemic stroke: Results from two multicenter studies in China.

Background and Objectives: The Alberta Stroke Program CT Score (ASPECTS) is a widely used rating system for assessing infarct extent and location. We aimed to investigate the prognostic value of ASPECTS subregions' involvement in the long-term functional outcomes of acute ischemic stroke (AIS). Materials and Methods: Consecutive patients with AIS and anterior circulation large-vessel stenosis and occlusion between January 2019 and December 2020 were included. The ASPECTS score and subregion involvement for each patient was assessed using posttreatment magnetic resonance diffusion-weighted imaging. Univariate and multivariable regression analyses were conducted to identify subregions related to 3-month poor functional outcome (modified Rankin Scale scores, 3-6) in the reperfusion and medical therapy cohorts, respectively. In addition, prognostic efficiency between the region-based ASPECTS and ASPECTS score methods were compared using receiver operating characteristic curves and DeLong's test. Results: A total of 365 patients (median age, 64 years; 70% men) were included, of whom 169 had poor outcomes. In the reperfusion therapy cohort, multivariable regression analyses revealed that the involvement of the left M4 cortical region in left-hemisphere stroke (adjusted odds ratio [aOR] 5.39, 95% confidence interval [CI] 1.53-19.02) and the involvement of the right M3 cortical region in right-hemisphere stroke (aOR 4.21, 95% CI 1.05-16.78) were independently associated with poor functional outcomes. In the medical therapy cohort, left-hemisphere stroke with left M5 cortical region (aOR 2.87, 95% CI 1.08-7.59) and caudate nucleus (aOR 3.14, 95% CI 1.00-9.85) involved and right-hemisphere stroke with right M3 cortical region (aOR 4.15, 95% CI 1.29-8.18) and internal capsule (aOR 3.94, 95% CI 1.22-12.78) affected were related to the increased risks of poststroke disability. In addition, region-based ASPECTS significantly improved the prognostic efficiency compared with the conventional ASPECTS score method. Conclusion: The involvement of specific ASPECTS subregions depending on the affected hemisphere was associated with worse functional outcomes 3 months after stroke, and the critical subregion distribution varied by clinical management. Therefore, region-based ASPECTS could provide additional value in guiding individual decision making and neurological recovery in patients with AIS.

Two telomere-to-telomere gapless genomes reveal insights into Capsicum evolution and capsaicinoid biosynthesis.

Chili pepper (Capsicum) is known for its unique fruit pungency due to the presence of capsaicinoids. The evolutionary history of capsaicinoid biosynthesis and the mechanism of their tissue specificity remain obscure due to the lack of high-quality Capsicum genomes. Here, we report two telomere-to-telomere (T2T) gap-free genomes of C. annuum and its wild nonpungent relative C. rhomboideum to investigate the evolution of fruit pungency in chili peppers. We precisely delineate Capsicum centromeres, which lack high-copy tandem repeats but are extensively invaded by CRM retrotransposons. Through phylogenomic analyses, we estimate the evolutionary timing of capsaicinoid biosynthesis. We reveal disrupted coding and regulatory regions of key biosynthesis genes in nonpungent species. We also find conserved placenta-specific accessible chromatin regions, which likely allow for tissue-specific biosynthetic gene coregulation and capsaicinoid accumulation. These T2T genomic resources will accelerate chili pepper genetic improvement and help to understand Capsicum genome evolution.

Inhibition of ROS/caspase-3/GSDME-mediated pyroptosis alleviates high glucose-induced injury in AML-12 cells.

Diabetic liver injury (DLI) is a chronic complication of the liver caused by diabetes, and its has become one of the main causes of nonalcoholic fatty liver disease (NAFLD). The gasdermin E (GSDME)-dependent pyroptosis signaling pathway is involved in various physiological and pathological processes; however, its role and mechanism in DLI are still unknown. This study was performed to investigate the role of GSDME-mediated pyroptosis in AML-12 cell injury induced by high glucose and to evaluate the therapeutic potential of caspase-3 inhibition for DLI. The results showed that high glucose activated apoptosis by regulating the apoptotic protein levels including Bax, Bcl-2, and enhanced cleavage of caspase-3 and PARP. Notably, some of the hepatocytes treated with high glucose became swollen, accompanied by GSDME-N generation, indicating that pyroptosis was further induced by active caspase-3. Moreover, the effects of high glucose on AML-12 cells could be partly reversed by a reactive oxygen scavenger (NAC) and caspase-3 specific inhibitor (Z-DEVD-FMK), which suggests high glucose induced GSDME-dependent pyroptosis in AML-12 cells through increasing ROS levels and activating caspase-3. In conclusion, our results show that high glucose can induce pyroptosis in AML-12 cells, at least in part, through the ROS/caspase-3/GSDME pathway，and inhibition of caspase-3 can ameliorate high glucose-induced hepatocyte injury, providing an important basis for clarifying the pathogenesis and treatment of DLI.

Effect of support structure of Pt/silicaite-1 catalyst on non-thermal plasma (NTP) assisted chlorobenzene degradation and PCDD/Fs formation.

Development of efficient catalysts for non-thermal plasma (NTP) assisted catalysis to mitigate the formation of harmful by-products is a significant challenge in the degradation of chlorinated volatile organic compounds (Cl-VOCs). In this study, catalytically active Pt nanoparticles supported on non-porous SiO2 and silicalite-1 zeolites (S1) with different pore structure were comparatively investigated for catalytic chlorobenzene degradation under NTP condition. It was shown that the pore structure could significantly impact the metal size and metal dispersion rate. Pt supported on modified S1 hierarchical meso-micro-porous silicalite-1 (Pt/D-S1) exhibited the smallest particle size (∼6.19 nm) and the highest dispersion rate (∼1.87). Additionally, Pt/D-S1 demonstrated superior catalytic performance compared to the other catalysts, achieving the highest chlorobenzene conversion and COx selectivity at about 80% and 75%, respectively. Furthermore, the pore structure also affected the formation of by-products according to the findings from GC-MS analysis. Pt/SiO2 generated a total of 18 different species of organic compounds, whereas only 12 species of organic by-products were identified in the Pt/D-S1 system (e.g. polychlorinated compounds like 3,4 dichlorophenol were exclusively identified in Pt/SiO2). Moreover, dioxin-like polychlorinated biphenyl and other chlorinated organic compounds, which have potential to form highly toxic dioxins, were detected in the catalysts. HRGC-HRMS confirmed and quantified the 17 different dioxin/furans formed on Pt/SiO2 (25,100 ng TEQ kg-1), Pt/S1 (515 ng TEQ kg-1) and Pt/D-S1 (367 ng TEQ kg-1). The correlation between synthesis-structure-performance in this study provides insights into the design of catalysts for deep oxidation of Cl-VOCs in NTP system.

Elucidating the Role of Transcriptomic Networks and DNA Methylation in Collagen Deposition of Dezhou Donkey Skin.

DNA methylation represents a predominant epigenetic modification with broad implications in various biological functions. Its role is particularly significant in the process of collagen deposition, a fundamental aspect of dermal development in donkeys. Despite its critical involvement, the mechanistic insights into how DNA methylation influences collagen deposition in donkey skin remain limited. In this study, we employed whole genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq) to investigate the epigenetic landscape and gene expression profiles in the dorsal skin tissues of Dezhou donkeys across three developmental stages: embryonic (YD), juvenile (2-year-old, MD), and mature (8-year-old, OD). Our analysis identified numerous differentially methylated genes that play pivotal roles in skin collagen deposition and overall skin maturation, including but not limited to COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, GLUL, SFRP2, FOSL1, SERPINE1, MMP1, MMP2, MMP9, and MMP13. Notably, we observed an inverse relationship between gene expression and DNA methylation proximal to transcription start sites (TSSs), whereas a direct correlation was detected in regions close to transcription termination sites (TTSs). Detailed bisulfite sequencing analyses of the COL1A1 promoter region revealed a low methylation status during the embryonic stage, correlating with elevated transcriptional activity and gene expression levels. Collectively, our findings elucidate key genetic markers associated with collagen deposition in the skin of Dezhou donkeys, underscoring the significant regulatory role of DNA methylation. This research work contributes to the foundational knowledge necessary for the genetic improvement and selective breeding of Dezhou donkeys, aiming to enhance skin quality attributes.

Cardiomyocyte Adaptation to Exercise: K+ Channels, Contractility and Ischemic Injury.

Cardiovascular disease is a leading cause of morbidity and mortality, and exercise-training (TRN) is known to reduce risk factors and protect the heart from ischemia and reperfusion injury. Though the cardioprotective effects of exercise are well-documented, underlying mechanisms are not well understood. This review highlights recent findings and focuses on cardiac factors with emphasis on K+ channel control of the action potential duration (APD), ß-adrenergic and adenosine regulation of cardiomyocyte function, and mitochondrial Ca2+ regulation. TRN-induced prolongation and shortening of the APD at low and high activation rates, respectively, is discussed in the context of a reduced response of the sarcolemma delayed rectifier potassium channel (IK) and increased content and activation of the sarcolemma KATP channel. A proposed mechanism underlying the latter is presented, including the phosphatidylinositol-3kinase/protein kinase B pathway. TRN induced increases in cardiomyocyte contractility and the response to adrenergic agonists are discussed. The TRN-induced protection from reperfusion injury is highlighted by the increased content and activation of the sarcolemma KATP channel and the increased phosphorylated glycogen synthase kinase-3ß, which aid in preventing mitochondrial Ca2+ overload and mitochondria-triggered apoptosis. Finally, a brief section is presented on the increased incidences of atrial fibrillation associated with age and in life-long exercisers.