Intensive aquaculture production generates large amounts of sludge. This waste could be considered as a potential source of nutrients that can be recovered and utilized. Little attention has been paid to nutrient recovery from fish sludge. In this study, bioconversion of sludge was evaluated in lab scale under anaerobic (AN), facultative anaerobic (FA) and aerobic (AE) conditions. After 40 days of fermentation, AN recovered the highest values of dissolved total nitrogen (82.7 mg L-1), while AE showed the highest dissolved total phosphorus (11.8 mg L-1) and the highest reduction of total suspended solids (36.0 %). Microbial analysis showed that AN exhibited a distinct bacterial community than that of FA and AE. Furthermore, C. sorokiniana grown in AN effluents collected after 12 days of fermentation achieved the highest biomass production (1.96 g L-1). These results suggest that AN has the best potential to recover nutrients from sludge for production of C. sorokiniana.
PURPOSE: To investigate the repeatability and agreement of corneal astigmatism measurements in eyes with irregular corneal astigmatism component (ICAC) using four devices: IOLMaster 700 biometer, Lenstar 900 biometer, iTrace, and Pentacam. DESIGN: Prospective cross-sectional reliability analysis. METHODS: Sixty-four eyes (52 patients) with ICAC were examined three times using the four devices. The eye with ICAC in this study is defined as the cornea has a certain degree of irregular astigmatism (asymmetric and/or skewed bowtie pattern of corneal topography according to corneal topography classification), accompanied with total corneal higher-order aberrations in the 4 mm zone of 0.3 µm or greater. Corneal astigmatism was evaluated using three categories: anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), and total corneal astigmatism (TCA). The repeatability was determined using the ∆Ast (arithmetic mean of vector differences among three repeated corneal astigmatism measurements). Bland-Altman plots and astigmatism vector analyses were employed to assess agreement. RESULTS: The IOLMaster 700 (∆Ast=0.27±0.20D) showcased higher repeatability in ACA measurements compared to iTrace (∆Ast=0.37±0.38D, P=0.040) and Pentacam (∆Ast=0.50±0.22D, P<0.001), and paralleled the performance of Lenstar 900 (∆Ast=0.31±0.26D, P=0.338). The Pentacam (∆Ast=0.09±0.07D, P<0.001) demonstrated superior repeatability in PCA, whereas the IOLMaster 700 (∆Ast=0.33±0.23D, P<0.001) excelled in TCA. The IOLMaster 700 exhibited good agreement with either Lenstar 900 or iTrace, characterized by narrow 95% limits of agreement and clinically acceptable vector differences. Conversely, vector differences between Pentacam and the other three devices in ACA and TCA measurements were clinically significant, exceeding 0.50D(all P<0.05). CONCLUSIONS: In terms of repeatability of corneal astigmatism measurements in eyes with irregular corneal astigmatism component, the IOLMaster 700 and Lenstar 900 outperformed iTrace and Pentacam. While the IOLMaster 700 can be used interchangeably with either Lenstar 900 or iTrace, the Pentacam is not interchangeable with the other three devices.
BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. METHODS: In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. RESULTS: From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). CONCLUSIONS: Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.
Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization.
We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.
Tick-borne orthoflaviviruses (TBFs) are classified into three conventional groups based on genetics and ecology: mammalian, seabird and probable-TBF group. Recently, a fourth basal group has been identified in Rhipicephalus ticks from Africa: Mpulungu flavivirus (MPFV) in Zambia and Ngoye virus (NGOV) in Senegal. Despite attempts, isolating these viruses in vertebrate and invertebrate cell lines or intracerebral injection of newborn mice with virus-containing homogenates has remained unsuccessful. In this study, we report the discovery of Xinyang flavivirus (XiFV) in Haemaphysalis flava ticks from Xìnyáng, Henan Province, China. Phylogenetic analysis shows that XiFV was most closely related to MPFV and NGOV, marking the first identification of this tick orthoflavivirus group in Asia. We developed a reverse transcriptase quantitative PCR assay to screen wild-collected ticks and egg clutches, with absolute infection rates of 20.75â% in adult females and 15.19â% in egg clutches, suggesting that XiFV could be potentially spread through transovarial transmission. To examine potential host range, dinucleotide composition analyses revealed that XiFV, MPFV and NGOV share a closer composition to classical insect-specific orthoflaviviruses than to vertebrate-infecting TBFs, suggesting that XiFV could be a tick-only orthoflavivirus. Additionally, both XiFV and MPFV lack a furin cleavage site in the prM protein, unlike other TBFs, suggesting these viruses might exist towards a biased immature particle state. To examine this, chimeric Binjari virus with XIFV-prME (bXiFV) was generated, purified and analysed by SDS-PAGE and negative-stain transmission electron microscopy, suggesting prototypical orthoflavivirus size (~50 nm) and bias towards uncleaved prM. In silico structural analyses of the 3'-untranslated regions show that XiFV forms up to five pseudo-knot-containing stem-loops and a prototypical orthoflavivirus dumbbell element, suggesting the potential for multiple exoribonuclease-resistant RNA structures.
Flavivirus , Ixodidae , Phylogeny , Animals , Flavivirus/genetics , Flavivirus/classification , Flavivirus/isolation & purification , China , Ixodidae/virology , Female
The effects of ultra-high pressure (UHP) pretreatment (50-250 MPa) on the fish curing were studied. UHP increased the overall volatile compound concentration of cured fish. Among 50-250 MPa five treatment groups, 150 MPa UHP group exhibited the highest total free amino acid content (294.34 mg/100 g) with that of the control group being 92.39 mg/100 g. The activity of cathepsin L was increased under 50-200 MPa UHP treatment (62.28-58.15 U/L), compared with that in the control group (53.80 U/L). UHP treatment resulted in a significant increase in small molecule compounds, especially the amino acid dipeptides and ATP metabolic products. Under UHP treatments, the bacterial phyla Actinobacteriota (1.04-5.25 %), Bacteroidota (0.20-4.47 %), and Deinococcota (0.00-0.05 %) exhibited an increased abundance, and they promoted taste and flavor formation. Our results indicated that UHP is a promising pretreatment method to improve taste and flavour in cured fish by affecting the microorganisms, cathepsin, and proteins.
A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.
Walnuts exhibit a higher resistance to diseases, though they are not completely immune. This study focuses on the Pectin methylesterase (PME) gene family to investigate whether it is involved in disease resistance in walnuts. These 21 genes are distributed across 12 chromosomes, with four pairs demonstrating homology. Variations in conserved motifs and gene structures suggest diverse functions within the gene family. Phylogenetic and collinear gene pairs of the PME family indicate that the gene family has evolved in a relatively stable way. The cis-acting elements and gene ontology enrichment of these genes, underscores their potential role in bolstering walnuts' defense mechanisms. Transcriptomic analyses were conducted under conditions of Cryptosphaeria pullmanensis infestation and verified by RT-qPCR. The results showed that certain JrPME family genes were activated in response, leading to the hypothesis that some members may confer resistance to the disease.
Reservoirs, heavily influenced by artificial management, often harbor phytoplankton assemblages dominated by cyanobacteria or dinoflagellates, triggering significant changes in aquatic ecosystems. However, due to limited sampling frequency and insufficient attention to species composition, the bloom processes and key characteristics of phytoplankton community structure have not been systematically elucidated. During the low-water level period when blooms are most likely to occur (June to September) in a tributary bay of the Three Gorges Reservoir, daily sampling was conducted to investigate phytoplankton community composition, identify significant environmental factors, and evaluate important structure characteristics of phytoplankton community. The results showed that Microcystis aeruginosa maintained a clear dominance for almost a month in stage 1, with low Shannon and evenness but a high dominance index. Phytoplankton total density and biomass decreased drastically in stage 2, but Microcystis aeruginosa still accounted for some proportion. The highest Shannon and evenness but the lowest dominance index occurred in stage 3. Peridiniopsis niei occurred massively in stage 4, but its dominant advantages lasted only one to two days. NH4-N was responsible for the dominance of Microcystis aeruginosa, while TP and PO4-P was responsible for the dominance of Peridiniopsis niei; however, precipitation contributed to their drastic decrease or disappearance to some extent. The TN : TP ratio could be considered as an important indicator to determine whether Microcystis aeruginosa or Peridiniopsis niei dominated the phytoplankton community. Throughout the study period, physiochemical factors explained more variation in phytoplankton data than meteorological and hydrological factors. Pairwise comparisons revealed an increase in average ß diversity with stage progression, with higher ß diversities based on abundance data than those based on presence/absence data. Repl had a greater effect on ß diversity differences based on presence/absence data, whereas RichDiff had a greater effect on ß diversity differences based on species abundance data. Co-occurrence networks for stage 1 showed the most complex structure, followed by stage 4, while the network for stage 3 was relatively sparse, although the overall community division remained compact. This study provides a useful attempt to explore the status and changes in phytoplankton community structure during the bloom process through high-resolution investigation.
Triple-negative breast cancer (TNBC) has greater infiltration of M2-like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co-localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL-4, IL-6, and other cytokines, in which the IL-4/IL-4R/STAT3/IL-6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL-4R/STAT3/IL-6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC.
Four new meroterpenoids, namely nivalones CF (1-4), along with a known meroterpenoid, cannabiorcicyclolic acid (5), were isolated from the branches and leaves of Rhododendron nivale. The chemical structures of compounds 1-4 were elucidated through comprehensive spectroscopic analyses, including NMR, UV-Vis, IR, ECD spectroscopy, as well as HR-ESI-MS. The isolated compounds were evaluated for their anti-inflammatory and neuroprotective properties. The inhibitory activity of compound 5 against lipopolysaccharide (LPS)-induced nitric oxide (NO) production was initially demonstrated, showcasing an IC50 value of 21.1 µM. Additionally, both compounds 2 and 5 displayed a notable effect on the viability of H2O2-damaged SH-SY5Y cells, indicating their significant neuroprotection effects.
Tobacco (Nicotiana tabacum L.) bacterial wilt, caused by Ralstonia solanacearum, is indeed a highly destructive plant disease, leading to substantial damage in tobacco production. While biological control is considered an effective measure for managing bacterial wilt, related research in this area has been relatively limited compared to other control methods. In order to discover new potential antagonistic bacteria with high biocontrol efficacy against tobacco bacterial wilt, we conducted an analysis of the microbial composition differences between disease-suppressive and disease-conducive soils using Illumina sequencing. As a result, we successfully isolated six strains from the disease-suppressive soil that exhibited antibacterial activity against Ralstonia solanacearum. Among these strains, B4-7 showed the strongest antibacterial activity, even at acidic conditions with a pH of 4.0. Based on genome analysis using Average Nucleotide Identity (ANI), B4-7 was identified as Bacillus velezensis. In greenhouse and field trials, strain B4-7 significantly reduced the disease index of tobacco bacterial wilt, with control efficiencies reaching 74.03% and 46.88% respectively. Additionally, B4-7 exhibited plant-promoting abilities that led to a 35.27% increase in tobacco production in field conditions. Quantitative real-time (qPCR) analysis demonstrated that strain B4-7 effectively reduced the abundance of R. solanacearum in the rhizosphere. Genome sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed that strain B4-7 potentially produces various lipopeptide metabolites, such as microlactin, bacillaene, difficidin, bacilysin, and surfactin. Furthermore, B4-7 influenced the structure of the rhizosphere soil microbial community, increasing bacterial abundance and fungal diversity, while also promoting the growth of different beneficial microorganisms. In addition, B4-7 enhanced tobacco's resistance to R. solanacearum by increasing the activities of defense enzymes, including superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Collectively, these findings suggest that B. velezensis B4-7 holds significant biocontrol potential and can be considered a promising candidate strain for eco-friendly management of tobacco bacterial wilt.
Krabbe disease (KD) is classed as the lysosomal storage disease with mutations in the galactosylceramidase (GALC) gene, and commonly showed as autosomal recessive pattern with 30-kb deletion in infantile subtype. In this case, we report a 39-years adult-onset KD (AOKD) patient with multiple sclerosis-like symptoms and neuroimaging changes. She carries the heterozygous mutations in GALC included a missense mutation of c.1901T>C from her mother, and a splicing mutation of c.908+5G>A from her father. The splicing mutations in KD are reviewed and confirmed that c.908+5G>A is a novel splicing mutation in AOKD.
Stretchable phosphorescence materials potentially enable applications in diverse advanced fields in wearable electronics. However, achieving room-temperature phosphorescence materials simultaneously featuring long-lived emission and good stretchability is challenging because it is hard to balance the rigidity and flexibility in the same polymer. Here we present a multiphase engineering for obtaining stretchable phosphorescent materials by combining stiffness and softness simultaneously in well-designed block copolymers. Due to the microphase separation, copolymers demonstrate an intrinsic stretchability of 712%, maintaining an ultralong phosphorescence lifetime of up to 981.11 ms. This multiphase engineering is generally applicable to a series of binary and ternary initiator systems with color-tunable phosphorescence in the visible range. Moreover, these copolymers enable multi-level volumetric data encryption and stretchable afterglow display. This work provides a fundamental understanding of the nanostructures and material properties for designing stretchable materials and extends the potential of phosphorescence polymers.
The retina consumes massive amounts of energy, yet its metabolism and substrate exploitation remain poorly understood. Here, we used a murine explant model to manipulate retinal energy metabolism under entirely controlled conditions and utilised 1H-NMR spectroscopy-based metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experimental manipulations resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected. This selective vulnerability of photoreceptors suggested very specific adaptations in their energy metabolism. Rod photoreceptors were found to rely strongly on oxidative phosphorylation, but only mildly on glycolysis. Conversely, cone photoreceptors were dependent on glycolysis but insensitive to electron transport chain decoupling. Importantly, photoreceptors appeared to uncouple glycolytic and Krebs-cycle metabolism via three different pathways: (1) the mini-Krebs-cycle, fuelled by glutamine and branched chain amino acids, generating N-acetylaspartate; (2) the alanine-generating Cahill-cycle; (3) the lactate-releasing Cori-cycle. Moreover, the metabolomics data indicated a shuttling of taurine and hypotaurine between the retinal pigment epithelium and photoreceptors, likely resulting in an additional net transfer of reducing power to photoreceptors. These findings expand our understanding of retinal physiology and pathology and shed new light on neuronal energy homeostasis and the pathogenesis of neurodegenerative diseases.
Citric Acid Cycle , Glycolysis , Oxidative Phosphorylation , Retina , Animals , Mice , Retina/metabolism , Energy Metabolism , Metabolomics , Retinal Pigment Epithelium/metabolism , Retinal Rod Photoreceptor Cells/metabolism , Mice, Inbred C57BL , Retinal Cone Photoreceptor Cells/metabolism
Aglaonema commutatum is a famous species in the Aglaonema genus, which has important ornamental and economic value. However, its chloroplast genome information and phylogenetic relationships among popular green cultivars of Aglaonema in southern China have not been reported. Herein, chloroplast genomes of one variety of A. commutatum and seven green cultivars of Aglaonema, namely, A. commutatum 'San Remo', 'Kai Sa', 'Pattaya Beauty', 'Sapphire', 'Silver Queen', 'Snow White', 'White Gem', and 'White Horse Prince', were sequenced and assembled for comparative analysis and phylogeny. These eight genomes possessed a typical quadripartite structure that consisted of a LSC region (90,799-91,486 bp), an SSC region (20,508-21,137 bp) and a pair of IR regions (26,661-26,750 bp). Each genome contained 112 different genes, comprising 79 protein-coding genes, 29 tRNA genes and 4 rRNA genes. The gene orders, GC contents, codon usage frequency, and IR/SC boundaries were highly conserved among these eight genomes. Long repeats, SSRs, SNPs and indels were analyzed among these eight genomes. Comparative analysis of 15 Aglaonema chloroplast genomes identified 7 highly variable regions, including trnH-GUG-exon1-psbA, trnS-GCU-trnG-UCC-exon1, trnY-GUA-trnE-UUC, psbC-trnS-UGA, trnF-GAA-ndhJ, ccsA-ndhD, and rps15-ycf1-D2. Reconstruction of the phylogenetic trees based on chloroplast genomes, strongly supported that Aglaonema was a sister to Anchomanes, and that the Aglaonema genus was classified into two sister clades including clade I and clade II, which corresponded to two sections, Aglaonema and Chamaecaulon, respectively. One variety and five cultivars, including A. commutatum 'San Remo', 'Kai Sa', 'Pattaya Beauty', 'Silver Queen', 'Snow White', and 'White Horse Prince', were classified into clade I; and the rest of the two cultivars, including 'Sapphire' and 'White Gem', were classified into clade II. Positive selection was observed in 34 protein-coding genes at the level of the amino acid sites among 77 chloroplast genomes of the Araceae family. Based on the highly variable regions and SSRs, 4 DNA markers were developed to differentiate the clade I and clade II in Aglaonema. In conclusion, this study provided chloroplast genomic resources for Aglaonema, which were useful for its classification and phylogeny.
Genome, Chloroplast , Phylogeny , Genomics/methods , Genetic Markers , Chloroplasts/genetics , Base Composition , Microsatellite Repeats/genetics
BACKGROUND: Sodium-dependent glucose transporter (SGLT2) inhibitors (SGLT2i) have been found to have anti-atherosclerotic effects in clinical treatment. OBJECTIVES: The aim of this study was to explore whether angiotensin II (Ang II) induces changes in the expression of Na+/H+ exchanger of cytoplasmic membrane channel proteins (NHE1) and SGLT2 in macrophages and whether dapagliflozin (DAPA), an SGLT2i, protects against Ang II induced macrophage senescence by inhibiting NHE1 activation to alleviate Atherosclerosis (AS). METHODS: After intervention with DAPA plus gavage or feeding them a high-fat diet, the mice's aortas were dissected, and oil red O staining was performed. Cell proliferation and toxicity detection, western blot, immunofluorescence, and ß-galactosidase staining methods were adopted to detect cell activity, expressions of senescence-related genes, and number of senescent cells after different concentrations of Ang II or DAPA or plasmid NHE1 were treated with RAW264.7 cells. RESULTS: (1) The formation of AS plaques in ApoE -/- mice showed a downward trend under DAPA. (2) After the intervention of Ang II, the cell activity of RAW264.7 decreased, and the expression of senescent cells and related genes increased. (3) Under the Ang II condition, the expression of SGLT2 and NHE1 increased, and SGLT2, NHE1, and senescence-related genes decreased with the addition of DAPA. (4) The expression of NHE1, senescent cells and related genes decreased in RAW264.7 cells after DAPA treatment with plasmid NHE1 intervention. CONCLUSION: SGLT2i alleviates atherosclerosis by inhibiting NHE1 activation to protect against macrophage senescence induced by Ang II.
Background: Evidence of the relationship between platelet count and 30-day in-hospital mortality in ICU stroke patients is still scarce. Therefore, the purpose of this study was to explore the relationship between platelet count and 30-day in-hospital mortality among ICU stroke patients. Methods: We conducted a multicenter retrospective cohort study using data from 8,029 ICU stroke patients in the US eICU-CRD v2.0 database from 2014 to 2015. Utilizing binary logistic regression, smooth curve fitting, and subgroup analyses, we examined the link between platelet count and 30-day in-hospital mortality. Results: The 30-day in-hospital mortality prevalence was 14.02%, and the mean platelet count of 223 × 109/L. Adjusting for covariates, our findings revealed an inverse association between platelet count and 30-day in-hospital mortality (OR = 0.975, 95% CI: 0.966, 0.984). Subgroup analyses supported the robustness of these results. Moreover, a nonlinear relationship was observed between platelet count and 30-day in-hospital mortality, with the inflection point at 163 × 109/L. On the left side of the inflection point, the effect size (OR) was 0.92 (0.89, 0.95), while on the right side, the relationship was not statistically significant. Conclusion: This study establishes an independent negative association between platelet count and 30-day in-hospital mortality in ICU stroke patients. Furthermore, a nonlinear relationship with a saturation effect was identified, suggesting that maintaining the platelet count around 163 × 109/L can reduce 30-day in-hospital mortality in these patients.
