Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Homeostasis of cytoplasmic crowding by cell wall fluidization and ribosomal counterions.

In bacteria, algae, fungi, and plant cells, the wall must expand in concert with cytoplasmic biomass production, otherwise cells would experience toxic molecular crowding1,2 or lyse. But how cells achieve expansion of this complex biomaterial in coordination with biosynthesis of macromolecules in the cytoplasm remains unexplained3, although recent works have revealed that these processes are indeed coupled4,5. Here, we report a striking increase of turgor pressure with growth rate in E. coli, suggesting that the speed of cell wall expansion is controlled via turgor. Remarkably, despite this increase in turgor pressure, cellular biomass density remains constant across a wide range of growth rates. By contrast, perturbations of turgor pressure that deviate from this scaling directly alter biomass density. A mathematical model based on cell wall fluidization by cell wall endopeptidases not only explains these apparently confounding observations but makes surprising quantitative predictions that we validated experimentally. The picture that emerges is that turgor pressure is directly controlled via counterions of ribosomal RNA. Elegantly, the coupling between rRNA and turgor pressure simultaneously coordinates cell wall expansion across a wide range of growth rates and exerts homeostatic feedback control on biomass density. This mechanism may regulate cell wall biosynthesis from microbes to plants and has important implications for the mechanism of action of antibiotics6.

Stability between single and segmental maxillary osteotomies in bimaxillary surgery for cleft-associated class III deformity: a CBCT study.

OBJECTIVE: Segmental Le Fort I osteotomy through the cleft is a common strategy to narrow the alveolar cleft in adults. This study compared skeletal stability between single and segmental Le Fort I osteotomies in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: This retrospective analysis examined 45 adults with complete UCLP-associated class III deformities who underwent bimaxillary surgery with either single (n = 30) or segmental (n = 15) Le Fort I advancement. Cone beam computed tomography (CBCT) scans of the facial skeleton were acquired before surgery, 1-week postsurgery, and at follow-up. Measures of landmarks from the CBCT images for the two treatment groups were compared for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch). RESULTS: Postsurgery, the downward movement of the maxilla was larger in the segmental group than the single group. At follow-up, the maxilla moved backward in both groups, and upward in the segmental group. The mandible moved forward and upward and rotated upward in both groups. The amount of upward movement and rotation was larger in the segmental group than the single group. CONCLUSIONS: Two years after bimaxillary surgery in patients with UCLP-associated class III deformity, greater relapse was found after segmental Le Fort I osteotomies in vertical translation of the maxilla and mandible, and pitch rotation of the mandible compared with single Le Fort I osteotomies. CLINICAL RELEVANCE: The vertical relapse of the maxilla was larger after segmental Le Fort I advancement compared with single Le Fort I advancement in clefts.

Loss of the TRPM4 channel in humans causes immune dysregulation with defective monocyte migration.

BACKGROUND: Transient receptor potential melastatin subfamily member 4 (TRPM4) is a broadly expressed, calcium-activated, monovalent cation channel that regulates immune cell function in mice and cell lines. Clinically however, partial loss or gain of function mutations in TRPM4 lead to arrythmia and heart disease, with no documentation of immunological disorders. OBJECTIVE: To characterize the functional cellular mechanisms underlying the immune dysregulation phenotype in a proband with a mutated trpm4 gene. METHODS: We employ a combination of biochemical, cell biological, imaging, omics analyses, flow cytometry, and gene editing approaches. RESULTS: We report the first human cases with complete loss of the TRPM4 channel leading to immune dysregulation with frequent bacterial and fungal infections. Single cell and bulk RNAseq point to altered expression of genes affecting cell migration, specifically in monocytes. Inhibition of TRPM4 in T cells and the THP1 monocyte cell line reduces migration. More importantly primary T cells and monocytes from the TRPM4 patients migrate poorly. Finally, CRISPR knockout of TRPM4 in THP1 cells greatly reduces their migration potential. CONCLUSION: Our results demonstrate that TRPM4 plays a critical role in regulating immune cell migration, leading to increased susceptibility to infections.

The relationship between alcohol consumption and amygdala volume in a community-based sample.

Most prior studies have reported decreased amygdala volume in those with a history of alcohol use disorder. Decreased amygdala volume associated with alcohol use disorder may be related to an increased risk of addiction and relapse. However, the relationship between amygdala volume and a broad range of alcohol consumption is largely unexplored. The present cross-sectional analysis investigates the relationship between amygdala volume and self-reported alcohol consumption in participants of the Dallas Heart Study, a community-based study of Dallas County, Texas residents. Brain imaging and survey data from participants (n = 2023) were obtained, and multiple linear regressions were performed with the average amygdala volume as the dependent variable and drinking status, drinking risk, drinks per week, and binge drinking as independent variables. Drinking risk was categorized such that low-risk constituted ≤ 14 drinks per week in men and ≤ 7 drinks per week in women, while > 14 drinks per week in men and > 7 drinks per week in women constituted high-risk. Age, sex, intracranial volume, body mass index, education, and Quick Inventory of Depressive Symptomatology-Self Report score were included in all models as covariates. No statistically significant (p ≤ .05) associations were observed between self-reported alcohol consumption and amygdala volume. The present study suggests non-significant relationships between self-reported alcohol consumption and amygdala volume when controlling for relevant demographic factors in a large, community-based sample.

Integrative Single Cell Atlas Revealed Intratumoral Heterogeneity Generation from an Adaptive Epigenetic Cell State in Human Bladder Urothelial Carcinoma.

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) contributes to therapy resistance and immune evasion affecting clinical prognosis. The molecular and cellular mechanisms contributing to BLCA ITH generation remain elusive. It is found that a TM4SF1-positive cancer subpopulation (TPCS) can generate ITH in BLCA, evidenced by integrative single cell atlas analysis. Extensive profiling of the epigenome and transcriptome of all stages of BLCA revealed their evolutionary trajectories. Distinct ancestor cells gave rise to low-grade noninvasive and high-grade invasive BLCA. Epigenome reprograming led to transcriptional heterogeneity in BLCA. During early oncogenesis, epithelial-to-mesenchymal transition generated TPCS. TPCS has stem-cell-like properties and exhibited transcriptional plasticity, priming the development of transcriptionally heterogeneous descendent cell lineages. Moreover, TPCS prevalence in tumor is associated with advanced stage cancer and poor prognosis. The results of this study suggested that bladder cancer interacts with its environment by acquiring a stem cell-like epigenomic landscape, which might generate ITH without additional genetic diversification.

Boosting Efficiency in Piezo-Photocatalysis Process Using Poled Ba0.7Sr0.3TiO3 Nanorod Arrays for Pollutant Degradation and Hydrogen Production.

Recently, the combination of the piezoelectric effect in the photocatalytic process, referred to as piezo-photocatalysis, has gained considerable attention as a promising approach for enhancing the degradation of organic pollutants. In this investigation, we studied the piezo-photocatalysis by fabricating arrays of barium strontium titanate (Ba0.7Sr0.3TiO3) nanorods (BST NRs) on a glass substrate as recoverable catalysts. We found that the degradation rate constant k of the rhodamine B solution achieved 0.0447 min-1 using poled BST NRs in the piezo-photocatalytic process, indicating a 2-fold increase in efficiency compared to the photocatalytic process (0.00183 min-1) utilizing the same material. This is mainly ascribed to the generation of the piezopotential in the poled BST NRs under ultrasonic vibration. Moreover, the BST NR array demonstrated a hydrogen (H2) production rate of 411.5 µmol g-1 h-1. In the photoelectrochemical process, the photocurrent density of poled BST NRs achieved 1.97 mA cm-2 at an applied potential of 1.23 V (ERHE (reversible hydrogen electrode)) under ultrasonic vibrations, representing a 1.7-fold increase compared with the poled BST NRs without ultrasonic vibrations. The measurement results from the liquid chromatograph mass spectrometer (LC-MS) demonstrated the formulation of a degradation pathway for rhodamine B molecules. Moreover, ab initio molecular dynamics (AIMD) simulation results demonstrate the dominance of hydroxyl radicals (•OH) rather than superoxide radicals (•O2-) in the degradation process. This study not only benefits the understanding of the principle of the piezo-photocatalytic process but also provides a new perspective for improving the catalytic efficiency for organic pollutants degradation.

Differentiation and characterization of healthy versus pathological tau using chemical exchange saturation transfer.

Neurofibrillary tangles of tau constitute one of the key biological hallmarks of Alzheimer's disease. Currently, the assessment of regional tau accumulation requires intravenous administration of radioactive tracers for PET imaging. A noninvasive MRI-based solution would have significant clinical implications. Herein, we utilized an MRI technique known as chemical exchange saturation transfer (CEST) to determine the imaging signature of tau in both its monomeric and pathologic fibrillated conformations. Three sets of purified recombinant full-length (4R) tau protein were prepared for collection of CEST spectra using a 9.4 T NMR spectrometer at varying temperatures (25, 37, and 42 °C) and RF intensities (0.7, 1.0, 1.5, and 2.2 µT). Monomeric and fibrillated tau were readily distinguished based on their Z-spectrum profiles. Fibrillated tau demonstrated a less prominent peak at 3.5 ppm with additional peaks near 0.5 and 1.5 ppm. No significant differences were identified between fibrillated tau prepared using heparin versus seed-competent tau. In conclusion, monomeric and fibrillated tau can be readily detected and distinguished based on their CEST-derived Z-spectra, pointing to the potential utility of CEST-MRI as a noninvasive biomarker of regional pathologic tau accumulation in the brain. Further testing and validation in vitro and in vivo will be necessary before this can be applied clinically.

Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

The associations between type 2 diabetes and plasma biomarkers of Alzheimer's disease in the Health and Aging Brain Study: Health Disparities (HABS-HD).

Alzheimer's disease (AD) affects Latinos disproportionately. One of the reasons underlying this disparity may be type 2 diabetes (T2D) that is a risk factor for AD. The purpose of this study was to examine the associations of T2D and AD blood biomarkers and the differences in these associations between Mexican Americans and non-Hispanic Whites. This study was a secondary analysis of baseline data from the observational Health and Aging Brain Study: Health Disparities (HABS-HD) that investigated factors underlying health disparities in AD in Mexican Americans in comparison to non-Hispanic Whites. HABS-HD participants were excluded if they had missing data or were large outliers (z-scores >|4|) on a given AD biomarker. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels were measured from clinical labs. T2D was diagnosed by licensed clinicians. Plasma amyloid-beta 42 and 40 (Aß42/42) ratio, total tau (t-tau), and neurofilament light (NfL) were measured via ultra-sensitive Simoa assays. The sample sizes were 1,552 for Aß42/40 ratio, 1,570 for t-tau, and 1,553 for NfL. Mexican Americans were younger (66.6±8.7 vs. 69.5±8.6) and had more female (64.9% female vs. 55.1%) and fewer years of schooling (9.5±4.6 vs. 15.6±2.5) than non-Hispanic Whites. Mexican Americans differed significantly from non-Hispanic Whites in blood glucose (113.5±36.6 vs. 99.2±17.0) and HbA1c (6.33±1.4 vs. 5.51±0.6) levels, T2D diagnosis (35.3% vs. 11.1%), as well as blood Aß42/40 ratio (.051±.012 vs. .047±.011), t-tau (2.56±.95 vs. 2.33±.90), and NfL levels (16.3±9.5 vs. 20.3±10.3). Blood glucose, blood HbA1c, and T2D diagnosis were not related to Aß42/40 ratio and t-tau but explained 3.7% of the variation in NfL (p < .001). Blood glucose and T2D diagnosis were not, while HbA1c was positively (b = 2.31, p < .001, ß = 0.26), associated with NfL among Mexican Americans. In contrast, blood glucose, HbA1c, and T2D diagnosis were negatively (b = -0.09, p < .01, ß = -0.26), not (b = 0.34, p = .71, ß = 0.04), and positively (b = 3.32, p < .01, ß = 0.33) associated with NfL, respectively in non-Hispanic Whites. To conclude, blood glucose and HbA1c levels and T2D diagnosis are associated with plasma NfL levels, but not plasma Aß and t-tau levels. These associations differ in an ethnicity-specific manner and need to be further studied as a potential mechanism underlying AD disparities.

GmMATE100 Is Involved in the Import of Soyasaponins A and B into Vacuoles in Soybean Plants (Glycine max L.).

Triterpenoid saponins, synthesized via the mevalonic acid (MVA) pathway in the cytoplasm, provide protection against pathogens and pests in plants and health benefits for humans. However, the mechanisms by which triterpenoid saponins are transported between cellular compartments remain uncharacterized. Here, we characterize a tonoplast localized multidrug and toxic compound extrusion transporter, GmMATE100 (encoded by Glyma.18G143700), from soybean (Glycine max L.). GmMATE100 is co-expressed with soyasaponin biosynthetic genes, and its expression was induced by MeJA treatment, which also led to soyasaponin accumulation in soybean roots. GmMATE100 efficiently transports multiple type-B soyasaponins as well as type-A soyasaponins with low affinity from the cytosol to the vacuole in a yeast system. The GmMATE100 loss-of-function mutant showed a significant decrease in type-A and type-B soyasaponin contents in soybean roots. This study not only characterized the first soybean triterpenoid saponin transporter but also provided new knowledge for the rational engineering of soyasaponin content and composition in soybean plants to modulate their levels within crop environments.

An up-conversion fluorescence lateral-flow immunoassay for rapid detection of Daratumumab in serum protein electrophoresis clinical samples.

BACKGROUND: Daratumumab (DARA) is a commonly used monoclonal antibody (mAb) drug for the treatment of multiple myeloma (MM). Its appearance as a visible abnormal band in the γ-region of a serum protein electrophoresis (SPEP) gel may interfere with the SPEP result interpretation. With the advantages of portability and rapid testing capabilities, up-conversion fluorescence lateral-flow immunoassay (LFA) can be an ideal solution to detect DARA interference. METHODS: An up-conversion fluorescence LFA strip was designed and constructed to perform semi-quantitative DARA testing in clinical samples. The LFA strip test was evaluated for limit of detection (LOD), dynamic range, and analytical interference. RESULTS: To demonstrate the clinical utility of the LFA strip, 43 SPEP-positive patient serum samples were tested for the presence of DARA, and the results exactly matched the DARA usage history in patient medical records. CONCLUSIONS: The performance of the up-conversion fluorescence LFA strip meets the purpose of clarifying DARA interference in SPEP results. It may be used as an independent and objective confirmation of the presence of DARA in clinical samples. The LFA strip offers a cost-effective rapid on-site test to check for DARA interference alongside standard SPEP equipment, which significantly improves the interpretation of ambiguous SPEP results involving DARA, and does not intervene the current SPEP workflow in clinical laboratory practice.

Bioinspired 1T-MoS2-based aerogel beads for efficient freshwater harvesting in harsh environments.

Freshwater scarcity is one of the most critical issues worldwide, particularly in arid regions, stemming from population growth and climate change. Inspired by the hydrophilic bump structures of desert beetles, 1T-MoS2-based aerogel beads with porous structures and CaCl2-crystal loading (termed as MoAB-m@CaCl2-n) were prepared for freshwater harvesting. Metallic-phase MoS2 nanospheres exhibit excellent photothermal conversion abilities, facilitating solar-driven water desorption and evaporation. Owing to the synergistic effect of its localized surface features, hydrophilic groups, and dispersive CaCl2 particles, MoAB-2@CaCl2-2 efficiently harvests water from atmosphere with a superior moisture adsorption capacity (0.18-0.82 g g-1) at a wide range of relative humidity (10 %-70 %). Under one-sun illumination, MoAB-2@CaCl2-2 demonstrates an outstanding solar-driven water evaporation rate of 2.25 kg m-2h-1. The water evaporation rate from soil (water content = 20 %) is 1.19 kg m-2h-1, which is sufficient for sustainable freshwater generation from the soil in arid regions. More importantly, the multifunctional MoAB-2@CaCl2-2-based homemade freshwater generation prototype delivers a certain amount of water harvesting (0.99 g g-1 day-1) on a rainy day and provides an impressive daily freshwater yield (53.7 kg m-2) under natural sunlight. The integrated device exhibits excellent efficiency and practicality and offers a feasible method for freshwater harvesting in harsh environments.

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

S-scheme NiO/C3N5 heterojunctions with enhanced interfacial electric field for boosting photothermal-assisted photocatalytic H2 and H2O2 production.

Heterostructured visible-light-responsive photocatalysts represent a prospective approach to achieve efficient solar-to-chemical energy conversion. Herein, we propose a facile self-assembly technique to synthesize NiO nanoparticles/C3N5 nanosheets (NOCN) heterojunctions for hydrogen (H2) evolution catalysis and hydrogen peroxide (H2O2) production under visible light. In this regard, the black NiO nanoparticles (NPs) were tightly anchored on the surface of C3N5 nanosheets (CNNS) to construct S-scheme NOCN heterojunction, enabling efficient charge separation and high redox capability. Obtained results elucidated that the incorporated NiO NPs significantly promote light-harvesting efficiency and photo-to-thermal capacity over the NOCN composites. The enhanced photothermal effect facilitates the charge carrier transfer rate across the heterojunction and boosts the surface reaction kinetics. Accordingly, the photocatalytic performances of CNNS for H2 release and H2O2 production can be manipulated by introducing NiO NPs. The modified photocatalytic properties of NOCN composites are ascribed to the synergistic effects of all integrated components and the S-scheme heterojunction formation. Impressively, the high H2 evolution photocatalysis efficiency of NOCN nano-catalysts in seawater certifies their potential environmental applicability. Among all, the 12-NOCN nano-catalyst exhibits a higher photocatalytic efficiency for H2 release (112.2 µmol∙g-1∙h-1) and H2O2 production (91.2 µmol∙L-1∙h-1). Besides, the 12-NOCN nano-catalyst reveals excellent recyclability and structural stability. Additionally, the possible mechanism for photothermal-assisted photocatalysis is proposed. This work affords a feasible pathway to design photothermal-assisted S-scheme heterojunctions for diverse photocatalytic applications.

Impact of Off-Hour Admission on In-Hospital Outcomes for Patients With Stroke Receiving Reperfusion Therapy in China.

BACKGROUND: The structure and staffing of hospitals greatly impact patient outcomes, with frequent changes occurring during nights and weekends. This retrospective cohort study assessed the impact of admission timing on in-hospital management and outcomes for patients with stroke receiving reperfusion therapy in China using data from a nationwide registry. METHODS: Data from patients receiving reperfusion therapy were extracted from the Chinese Stroke Center Alliance. Hospital admission time was categorized according to day/evening versus night and weekday versus weekend. Primary outcomes were in-hospital death or discharge against medical advice, hemorrhage transformation, early neurological deterioration, and major adverse cardiovascular events. Logistic regression was performed to compare in-hospital management performance and outcomes based on admission time categories. RESULTS: Overall, 42 381 patients received recombinant tissue-type plasminogen activator (r-tPA) therapy, and 5224 underwent endovascular treatment (EVT). Patients admitted during nighttime had a higher probability of receiving r-tPA therapy within 4.5 hours from onset or undergoing EVT within 6 hours from onset compared with those admitted during day/evening hours (adjusted odds ratio, 1.04 [95% CI, 1.01-1.08]; P=0.021; adjusted odds ratio, 1.72 [95% CI, 1.59-1.86]; P<0.001, respectively). However, no significant difference was observed between weekend and weekday admissions for either treatment. No notable differences were noted between weekends and weekdays or nighttime and daytime periods in door-to-needle time for r-tPA or door-to-puncture time for EVT initiation. Furthermore, weekend or nighttime admission did not have a significant effect on the primary outcomes of r-tPA therapy or EVT. Nevertheless, in patients undergoing EVT, a higher incidence of pneumonia was observed among those admitted at night compared with those admitted during day/evening hours (adjusted odds ratio, 1.22 [95% CI, 1.05-1.42]; P=0.011). CONCLUSIONS: Patients admitted at nighttime were more likely to receive r-tPA therapy or EVT within the time window recommended in the guidelines. However, patients receiving EVT admitted at night had an increased risk of pneumonia.

Cancer-associated fibroblast-derived acetate promotes pancreatic cancer development by altering polyamine metabolism via the ACSS2-SP1-SAT1 axis.

The ability of tumour cells to thrive in harsh microenvironments depends on the utilization of nutrients available in the milieu. Here we show that pancreatic cancer-associated fibroblasts (CAFs) regulate tumour cell metabolism through the secretion of acetate, which can be blocked by silencing ATP citrate lyase (ACLY) in CAFs. We further show that acetyl-CoA synthetase short-chain family member 2 (ACSS2) channels the exogenous acetate to regulate the dynamic cancer epigenome and transcriptome, thereby facilitating cancer cell survival in an acidic microenvironment. Comparative H3K27ac ChIP-seq and RNA-seq analyses revealed alterations in polyamine homeostasis through regulation of SAT1 gene expression and enrichment of the SP1-responsive signature. We identified acetate/ACSS2-mediated acetylation of SP1 at the lysine 19 residue that increased SP1 protein stability and transcriptional activity. Genetic or pharmacologic inhibition of the ACSS2-SP1-SAT1 axis diminished the tumour burden in mouse models. These results reveal that the metabolic flexibility imparted by the stroma-derived acetate enabled cancer cell survival under acidosis via the ACSS2-SP1-SAT1 axis.

Circ-ABCA1 promotes oxidized low-density lipoprotein-induced inflammation and phenotypic switch in vascular smooth muscle cells.

OBJECTIVE: Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall, in which Human Vascular Smooth Muscle Cells (HVSMCs) are involved. Nevertheless, the functions and mechanisms of circRNAs in oxidized Low-Density Lipoprotein (ox-LDL)-induced vascular smooth muscle cells remain unclear. METHODS: Circ-ABCA1 expression was measured in the models of AS. Then, in the vitro model, oligonucleotide transfection was performed, followed by an analysis of VSMC proliferation, migration, inflammation, and phenotypic switch. Also, in the in vivo model, mice were injected with shRNA lentivirus, followed by histological examination of aortic tissues. Finally, the interaction of circ-ABCA1, miR-885-5p, and ROCK2 was identified. RESULTS: Circ-ABCA1, was confirmed to be overexpressed in ox-LDL-induced VSMCs and mouse models of AS. Functionally, silencing circ-ABCA1 via oligonucleotide transfection suppressed VSMC proliferation, migration, inflammation, and phenotypic switch in vitro and prevented AS development in mice in vivo. Mechanistically, circ-ABCA1 absorbed miR-885-5p, which targeted ROCK2. CONCLUSION: Taken together, the data from this study suggest that circ-ABCA1 mediates cellular inflammation and phenotype switching through the miR-885-5p/ROCK2 axis in ox-LDL-induced VSMCs, and the circ-ABCA1/miR-885-5p/ROCK2 axis is a new potential biomarker for the treatment of AS.

Impact of professional nursing interventions on clinical outcomes in patients with acute gastric bleeding: a retrospective analysis.

Acute gastric bleeding (AGB) is a common and potentially serious complication in patients with gastrointestinal disorders. Nursing interventions play a critical role in the management of acute gastric bleeding, but their impact on clinical outcomes is not well understood. The aim of this retrospective analysis was to evaluate the impact of nursing interventions on clinical outcomes in patients with acute gastric bleeding. A retrospective review of medical records was conducted for 220 patients with acute gastric bleeding who were admitted to the hospital between February 2022 and February 2023. Patients were divided into two groups based on whether or not they received nursing interventions during their hospital stay. Clinical outcomes, including length of hospital stay, blood transfusion requirements, and mortality rates, were compared between the two groups using descriptive statistics and logistic regression analysis. Of the 220 patients included in the study, 168 (76.4%) received nursing interventions during their hospital stay. Patients who received nursing interventions had a significantly shorter length of hospital stay (mean = 7.2 days, SD = 2.1) compared to those who did not receive nursing interventions (mean = 10.5 days, SD = 3.4, p < 0.001). Additionally, the 90-day mortality rate was lower in the group receiving professional nursing interventions (4.2% vs. 15.4%, p = 0.010). Fewer patients who received nursing interventions required blood transfusions (33.3% vs. 65.2%, p < 0.001) and mortality rates were lower (6.7% vs. 20.8%, p = 0.04). Multivariate logistic regression analysis suggested that professional nursing intervention was a protective factor for postoperative rebleeding in patients with gastric hemorrhage (OR 0.727, 95% CI 0.497-0.901, P < 0.001). The results of this retrospective analysis suggest that nursing interventions are associated with improved clinical outcomes in patients with acute gastric bleeding. The implementation of nursing interventions, such as individualized care plans, monitoring and evaluation, and patient education, should be encouraged to optimize patient outcomes in this population. Further research is needed to identify the most effective nursing interventions and to evaluate their cost-effectiveness.