A Chinese individual with DEL phenotype caused by a novel RHD allele.

BACKGROUND: RhD variants are categorized into partial D, weak D, and DEL. The detection of DEL can only be achieved through the adsorption and elution method or molecular techniques. Here, we report a case of DEL phenotypes associated with a novel allele in a Chinese individual. STUDY DESIGN AND METHODS: We used serological methods such as saline, indirect anti-human globulin, and adsorption-elution. The RHD genotype was determined by the PCR-sequence specific primer (PCR-SSP) method as well as the Sanger dideoxy sequencing. RESULTS: RBCs of the sample were found to be DEL phenotype by serological testing, with negative reactions in the saline and indirect anti-human globulin tests while positive reactions by the absorption-elution method. The genotyping results revealed a hemizygous (RHDc .1127 T>G/RHD-). The novel allele sequence has been submitted to GenBank (Accession number: OR608456). CONCLUSION: Our study demonstrates a case of a Chinese individual with DEL phenotype caused by a novel allele RHD c .1127 T > G. It expands the database of the DEL variant.

The safety and efficacy of indobufen or aspirin combined with clopidogrel in patients with acute myocardial infarction after percutaneous coronary intervention.

Currently, the standard treatment for patients who have undergone percutaneous coronary intervention (PCI) following acute myocardial infarction (MI) involves dual antiplatelet therapy (DAPT) with a combination of aspirin and a potent P2Y12 receptor inhibitor. However, the potential benefits of aspirin were partially constrained by the intolerance of some patients. The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.This retrospective study was conducted at a single center and utilized propensity score matching. The enrollment spanned from January 2019 to June 2022, incorporating patients with AMI after PCI. The participants were categorized into two groups based on discharged prescriptions: the aspirin DAPT group and the indobufen DAPT group. The primary endpoint focused on net adverse clinical event (NACE), defined as a composite outcome, including cardiac death, recurrence of MI, definite or probable stent thrombosis (ST), target lesion revascularization (TLR), ischemic stroke and Bleeding Academic Research Consortium (BARC) criteria type 2, 3, or 5. All the patients underwent a one-year follow-up period.A total of 1451 patients were enrolled in this study, with 258 assigned to the indobufen DAPT group and 1193 to the aspirin DAPT group. Following 1:1 propensity score matching, 224 patients were retained in each group. In the indobufen DAPT group, 58 individuals (25.9%) experienced the primary endpoint within one year, compared to 52 individuals (23.2%) in the aspirin DAPT group (HR 1.128, 95% CI 0.776-1.639, p = .527). Specifically, no significant differences were observed in either the efficacy endpoint (MACCE, 20.1% vs. 14.7%, HR 1.392, 95% CI 0.893-2.170, p = .146) or the safety endpoint (BARC 2,3 or 5, 8.04% vs. 10.30%, HR 0.779, p = .427). These findings remained consistent at 1, 3, or 6 months. Additionally, the incidence of gastrointestinal symptoms were significantly lower in indobufen DAPT group compared to the aspirin DAPT group (7.1% vs. 14.3%, p = .022).Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.

What is the context? Currently, the standard treatment for patients who have undergone percutaneous coronary intervention following acute myocardial infarction involves dual antiplatelet therapy with a combination of aspirin and a potent P2Y12 receptor inhibitor.However, the potential benefits of aspirin were partially constrained by the intolerance of some patients.The safety and efficacy of indobufen, an alternative antiplatelet agents to aspirin, in patients with AMI after PCI are yet to be thoroughly investigated.What is new? While both American and European clinical guidelines recommend the use of indobufen as an alternative treatment for patients who cannot tolerate aspirin, there exists a limited body of research on this subject.Our research is the first to address this gap by comparing the efficacy and safety of indobufen and aspirin in patients with AMI.Our research reveals that the efficacy and safety of indobufen are comparable to aspirin in Chinese patients with AMI following PCI. Given the potential advantages of indobufen in alleviating gastrointestinal symptoms, we propose it as a viable alternative for individuals intolerant to aspirin.What is the impact? These findings might pave the way for further exploration of alternatives to aspirin in patients with AMI.

Efficient CRISPR/Cas9-mediated ebony gene editing in the greater wax moth Galleria mellonella.

The greater wax moth, Galleria mellonella (Lepidoptera, Pyralidae), is a major bee pest that inflicts considerable harm on beehives, leading to economic losses. It also serves as a valuable resource insect and a model organism. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system plays a crucial role in improving economic insect breeding and developing efficient agricultural pest management systems in Lepidoptera. However, the CRISPR/Cas9 protocols have not been developed for G. mellonella. Here, the Gmebony knockout (KO) strain was established using the CRISPR/Cas9 genome editing system. We obtained Gmebony KO strain in the G4 generation, which took approximately 10 months. When compared with wild-type, the head, notum, and the terminal abdominal surface of 1st to 4th instar larvae in the KO strain changed from yellow to brown, and these regions of the KO strain gradually transformed into a black color from the 5th instar larvae, and the body color of the adult moth in the KO strain changed to black. The developmental period of the early larval and the following larval instars extended. The embryonic hatchability of the Gmebony KO strain was significantly decreased. The pupal body weight of the Gmebony KO strain was not affected. The feasibility of the CRISPR/Cas9 methodology was validated by single-target editing of Gmebony. Our findings provide the first evidence that the ebony gene can serve as a pigmentation reference gene for genetic modifications of G. mellonella. Meanwhile, it can be utilized in the development of genome editing control strategies and for gene function analyses in G. mellonella.

Clinical value of Tc-99m MDP SPECT/CT bone imaging for early diagnosis of Relapsing Polychondritis: a report of 5 cases.

BACKGROUND: Relapsing Polychondritis(RP) is a rare rheumatic immune disease. As with most diseases, if intervention is delayed, the patient's prognosis is worse. Currently, the diagnostic criteria used in clinical practice do not include CT, PET/CT, SPECT/CT and other new imaging examinations that have developed rapidly in recent years. However, these examinations have some special manifestations for RP, which can help clinicians diagnose RP earlier and distinguish it from other diseases. CASE PRESENTATION: These five RP patients all had respiratory symptoms such as cough and wheezing as the first symptom, which could not be diagnosed in time according to the previous diagnostic criteria. The clinical data of the five patients are listed in Table 1. The relatively specific manifestations of SPECT/CT examination provided clinicians with very valuable clues to help them advance the diagnosis time. CONCLUSIONS: The application of SPECT/CT bone imaging in early diagnosing RP proves to be effective, enabling clinicians to intervene promptly and enhance the overall well-being and quality of life for individuals affected by this condition.

Revealing the dual impact of VOCs on recycled rubber workers: Health risk and odor perception.

Volatile organic compounds (VOCs) pose potential hazards to human health and contribute significantly to odor pollution. This study examined VOC emissions from a representative recycled rubber industry, evaluating the occupational health risks for frontline workers in various workshops. Variables such as gender and workshop-specific concentration variations were considered using Monte Carlo simulation methods. Employees in the five production workshops and office areas face noncarcinogenic health risks with hazard indices (HIs) greater than 1, with the rubber compounding phase presenting the highest risk. Acetaldehyde is identified as the primary noncarcinogenic health risk substance, with hazard quotient (HQ) values exceeding 1 in all workshops. Carcinogenic health risks vary by area, with the highest risks found in compounding and refining workshops. Formaldehyde poses the greatest risk in rubber grinding workshops and offices, with cumulative weights exceeding unacceptable levels of M80.58 % and W77.56 % in grinding and M94.98 % and W92.24 % in the office. Male workers face 4-7 % greater noncarcinogenic VOC health risks than females and 5-14 % greater carcinogenic risks from individual VOCs, increasing their susceptibility to health risks caused by VOCs. Additionally, our analysis of odor identification and intensity classification revealed that 53 VOCs are capable of causing odor pollution, with several substances reaching odor levels of 2 or higher. The predominant perceived odors, as reflected in the odor wheel, include categories such as "solvent/aromatic" and "sweet/fruit," with aldehydes being the primary odor-causing substances. In summary, emissions of VOCs from rubber industrial processes not only pose substantial health risks to workers but also contribute significantly to odor pollution. Consequently, enterprises must prioritize optimizing workplace conditions to ensure the occupational health and well-being of their employees.

Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

BACKGROUND AND PURPOSE: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function-normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1-year outcomes in patients with acute ischemic stroke (AIS). METHODS: This is a prospective, multicenter observational study. Renal function-normalized SUA levels were determined by calculating the ratio of SUA to SCr. One-year outcomes included stroke recurrence, all-cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1-year stroke outcomes. RESULTS: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one-unit increase in SUA/SCr corresponded to a 19% decrease in 1-year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1-Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1-year stroke recurrence risks. The trend test indicated significant differences in the 1-year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all-cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1-year stroke recurrence. CONCLUSIONS: In patients with AIS, low SUA/SCr may be an independent risk factor for 1-year stroke recurrence. Changes in SUA/SCr had no significant impact on 1-year poor prognosis and all-cause mortality.

Robust detection of a rotational Doppler shift with randomly fluctuated light.

The complex external environment, such as obstruction and turbulence, poses significant limitations on the applications of rotational Doppler detection. The active manipulation of randomly fluctuated light has been proven effective in mitigating external environmental perturbations. Here, as an example, a partially coherent source with petal-like focal (or far) field distribution is constructed specifically for detecting rotational Doppler frequency shifts. The experiment involved conducting rotational Doppler detection under obstruction or turbulence conditions, and the results are compared with the fully coherent counterpart. The results demonstrate that the use of a partially coherent source can address the frequency-shift broadening problem due to the obstruction-induced beam information loss and mitigate it due to the turbulence-induced beam misalignment. These advantages make the proposed approach applicable to velocity metrology in complex environments.

A case of adrenal Castleman disease combined with liver cirrhosis and splenomegaly.

To describe a rare case of left adrenal Castleman disease (CD), splenomegaly, and cirrhosis. An examination revealed a left adrenal mass for more than three months, the patient, 44, was well-prepared for surgery after her left adrenal tumor was removed laparoscopically using a retroperitoneal approach, her postoperative pathology suggested that she had Castleman disease of the adrenal glands, and there had been no metastasis or recurrence during the six-month follow-up period. We have evaluated linked literature reports in this article, reporting relevant clinical knowledge regarding the disease and synthesizing previous research, in an effort to increase our understanding of it.

Safety of proteasome inhibitor drugs for the treatment of multiple myeloma post-marketing: a pharmacovigilance investigation based on the FDA adverse event reporting system.

BACKGROUND: The use of proteasome inhibitors (PIs), namely Bortezomib and Carfilzomib, revolutionized multiple myeloma (MM) treatment. Understanding their distinct adverse event (AE) profiles aids in tailored treatment plans. RESEARCH DESIGN AND METHODS: We analyzed FDA Adverse Event Reporting System (FAERS) data (Q1 2012-Q4 2023) for Bortezomib and Carfilzomib, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN). RESULTS: FAERS yielded 19,720 Bortezomib and 12,252 Carfilzomib AE reports. Males aged 45-65 exhibited higher AE susceptibility. Common AE systems included Infections, Nervous System Disorders, Blood Disorders, General Disorders, Cardiac Disorders, and Renal Disorders. New Bortezomib signals were sepsis and colitis. Carfilzomib exhibited elevated cardiac and renal toxicity but reduced peripheral neuropathy and thrombocytopenia. CONCLUSIONS: FAERS analysis revealed new AE signals (sepsis, colitis) for Bortezomib and highlighted Carfilzomib's heightened cardiac and renal risks compared to Bortezomib. Balancing PIs' benefits and risks is crucial for clinical decision-making.

A Nanoconfinement Strategy to Construct Co@CNTs for Lightweight and Ultra-Broadband Microwave Absorption.

The construction of stable and efficient nanocomposites with low addition and light weight has always been the goal pursued in the field of electromagnetic wave (EMW) absorption. In this study, the Co@CNTs nanocomposites with Co nanoparticles (13 nm) nanoconfined in the carbon nanotube (CNT) are successfully synthesized by a simple hydrothermal method and phenolic assisted pyrolysis method. The degree of graphitization of CNTs and the microstructure of Co nanoparticles can be effectively regulated by controlling the calcination temperature. The sample calcined at 700 °C can obtain excellent absorption performance at a low filling capacity of 10 wt.%: the minimum reflection loss (RL) is -41.2 dB and the effective absorption bandwidth (EAB) reaches a maximum width of 14.2 GHz. When the sample thickness is only 2.2 mm, the EAB of <-20 dB reaches 8.3 GHz, which is the maximum EAB of most current Co-based absorbers. In particular, the polarization and ferromagnetic coupling behaviors are elucidated in depth with the aid of electromagnetic field simulations using the High-Frequency Structure Simulator (HFSS). This work provides a new nanoconfinement strategy for constructing the Co@CNTs nanocomposites as lightweight and ultra-broadband absorbing materials for EMW protection and EMW pollution control.

Metabolic reprogramming of corn oligopeptide in regulating sodium nitrite-induced canine hepatocyte injury via TGF/NF-κB signaling pathways and aminoacyl-tRNA biosynthesis.

Sodium nitrite (SN), a prevalent food preservative, is known to precipitate hepatotoxicity upon exposure. This study elucidates the hepatoprotective effects of corn oligopeptide (COP) and vitamin E (VE) against SN-induced hepatic injury in canine hepatocytes. Canine liver cells were subjected to SN to induce hepatotoxicity, followed by treatment with COP and VE. Evaluations included assays for cell viability, oxidative stress markers, apoptosis, and inflammatory cytokines. Additionally, transcriptomic and metabolomic analyses were performed to delineate the underlying molecular mechanisms. The findings demonstrated that COP and VE significantly ameliorated SN-induced cytotoxicity, oxidative stress, and apoptosis. It was evidenced by restored cell viability, enhanced antioxidant enzyme activity, reduced cytoplasmic enzyme leakage, and decreased levels of malondialdehyde and inflammatory cytokines, with COP showing superior efficacy. The RNA sequencing revealed that COP treatment suppressed the SN-activated aminoacyl-tRNA biosynthesis pathway and TGF-ß/NF-κB signaling pathways, thereby mitigating amino acid depletion, apoptosis, and inflammation. Moreover, COP treatment upregulated genes associated with protein folding, bile acid synthesis, and DNA repair. Metabolomic analysis corroborated these results, showing that COP restored amino acid levels and enhanced bile acid metabolism, alleviating SN-induced metabolic disruptions. These findings offered significant insights into the protective mechanisms of COP underscoring its prospective application in treating liver injuries.

Clinical and electrocardiographic characteristics of immune checkpoint inhibitor-related myocarditis.

BACKGROUND: Immune checkpoint inhibitor (ICI) has become a major breakthrough in the field of tumor therapy, leading to improved survival. This study evaluated the clinical and electrocardiographic characteristics of patients with ICI-related myocarditis. METHODS: Patients with ICI-related myocarditis were enrolled from 4 centers in China until September 2023. Demographic data (age, sex, comorbidity), types of ICI, clinical manifestations, electrocardiogram (ECG) and treatment were analyzed retrospectively. Arrhythmia and characteristics of ECG were compared according to prognosis and grading. RESULTS: A total of 29 participants (13 females with a median age of 63.25 years) with ICI-related myocarditis were enrolled. Lung cancer was the most, with a proportion of 31.03 % (9/29). The median time from the first administration of ICI to the diagnosis of myocarditis was 50 days. Camrelizumab was the main type of ICI (9/29). Most patients had non-specific symptoms, dyspnea (n = 16) and palpitation (n = 9) were common. The overall mortality rate was 37.93 % (11/29) with a median follow-up of 9(4,11) days. Compared with the survivors, P-wave abnormality was more common in participants who were dead (24.14 %vs6.90 %, p = 0.010). A total of 19 patients with severe ICI-related myocarditis were included in this study. The proportions of sinus tachycardia (34.48 %vs0.00 %, p = 0.005), premature ventricular complex (27.59 %vs0.00 %, p = 0.027) and atrioventricular block (34.48 %vs3.45 %, p = 0.044) were higher in severe ICI-related myocarditis. CONCLUSIONS: Clinical manifestations of ICI-related myocarditis usually lacked specificity. ECGs can be manifested as new-onset arrhythmias, ST-T segment changes, fragmented QRS complex, abnormal P wave, prolonged QTc interval and multi­lead low voltage.

A transcriptional regulatory mechanism of genes in the tricarboxylic acid cycle in the heart.

The tricarboxylic acid (TCA) cycle plays a crucial role in mitochondrial ATP production in the healthy heart. However, in heart failure, the TCA cycle becomes dysregulated. Understanding the mechanism by which TCA cycle genes are transcribed in the healthy heart is an important prerequisite to understanding how these genes become dysregulated in the failing heart. PGC-1α is a transcriptional coactivator that broadly induces genes involved in mitochondrial ATP production. PGC-1α potentiates its effects through coactivation of coupled transcription factors, such as ERR, Nrf1, Gabpa, and YY1. We hypothesized that PGC-1α plays an essential role in transcription of TCA cycle genes. Thus, by utilizing localization peaks of PGC-1α to TCA cycle gene promoters, it would allow the identification of coupled transcription factors. PGC-1α potentiated the transcription of 13 out of 14 TCA cycle genes, partly through ERR, Nrf1, Gabpa, and YY1. ChIP-sequencing showed PGC-1α localization peaks in TCA cycle gene promoters. Transcription factors with binding elements that were found proximal to PGC-1α peak localization were generally essential for transcription of the gene. These transcription factor binding elements were well conserved between mice and humans. Among the four transcription factors, ERR and Gabpa played a major role in potentiating transcription when compared to Nrf1 and YY1. These transcription factor-dependent PGC-1α recruitment was verified with Idh3a, Idh3g, and Sdha promoters with DNA binding assay. Taken together, this study clarifies the mechanism by which TCA cycle genes are transcribed, which could be useful to understand how those genes are dysregulated in pathological conditions.

Core-shell magnetic covalent organic polymer nanocomposites as an adsorbent for the extraction of flavonoids.

A novel 3D magnetic nanocomposite material based on covalent organic polymers was successfully synthesized and utilized as an efficient sorbent for magnetic solid-phase extraction. It exhibited a regular core-shell structure, large specific surface area, superior stability, and paramagnetism. To evaluate its extraction efficiency, six flavonoids were tested, demonstrating maximum adsorption capacities ranging from 90 to 218 mg/g. Additionally, the material exhibited remarkable reusability and mechanical stability, maintaining its original state over eight cycles with consistent recovery. An analytical strategy combining magnetic solid-phase extraction with high performance liquid chromatography and tandem mass spectrometry was developed for the determination of flavonoids in orange, honey, soybean, and Dioscorea bulbifera L. samples. The low limits of detection (0.01-0.1 ng/mL) and limits of quantification (0.05-0.5 ng/mL), as well as satisfactory recovery (80.4-114.8%), were obtained. The linear range started from the limits of quantification to 500 ng/mL with R2 ≥ 0.9929. These results suggest that the prepared adsorbent possesses excellent adsorption capabilities for flavonoids, highlighting its significant potential for detecting these compounds in complex sample matrices.

Genome-wide association analysis to search for new loci associated with stroke risk in Northwestern Chinese population.

BACKGROUND AND PURPOSE: Genetic factors play an important role in the pathogenesis of stroke(S). This study aimed to screen the loci associated with S risk in northwestern Chinese population by genome-wide association analysis (GWAS). METHODS: A total of 1394 subjects, including 682 S patients and 692 controls, were enrolled in this study. SPSS 25.0 software was used for statistical analysis, and the independent sample t-test as well as Chi-square test were used to analyze the differences in age and gender between the case and control groups. The Precision Medicine Diversity Array (PMDA) genotyping chip was used in this study. The genotyping platform was the Gene Titan multi-channel instrument, and the Axiom Analysis Suite 6.0 software was used for the data analyzing. Besides, the LASSO analysis, SNP-SNP and GO/KEGG analysis were conducted to analyze the association between significant loci and S risk. RESULTS: A total of 30 SNPs were found to be associated with the S risk based on additive model (p < 5 × 10-8). After the LASSO screening, 22 SNPs showed the diagnostic value in S. The SNPs interaction analysis further screened the SNP-SNP interaction groups associated with the S risk(p < 0.05). Finally, the GO/KEGG analysis discovered the suggestive significance loci could be involved in the S development mainly by immune-related functions and pathways. CONCLUSION: This study discovered 30 S related SNPs and analyzed the potential pathways associated with genes located on the 30 SNPs, which were beneficial for enriching the genetic mechanism analysis of S in northwestern Chinese population.

Operation parameters and temperature affected sludge microbial metabolisms: An integrated perspective considering extracellular polymeric substances, soluble microbial products, biomass quantities, and community shifts.

Effluent soluble microbial products (SMP) and extracellular polymeric substances (EPS) are significant organics that pose challenges to advanced treatment processes. However, their production, transformation, and decomposition remain unclear due to their heterogeneity and the combined effects of environmental and operational factors. In this work, we investigated the impact of solids retention time (SRT), hydraulic retention time (HRT), and temperature on the changes in effluent SMP, with the consideration of the co-variation of EPS, sludge biomass, and community structures. Results show that longer SRT increased the biomass and relative abundance of functional microorganisms such as Myxococcota, Actinobacteria, and Terrimonas, which hindered EPS-to-SMP turnover and/or facilitated SMP consumption. This resulted in the accumulation of EPS and lower SMP concentrations at the beginning of the SRT adjustment. Both longer and shorter HRT (12 h and 8 h) led to increased SMP concentration, with the shorter HRT nearly doubling it (from approximately 6 to 12 mg/L), especially in terms of its protein and polysaccharide contents. Lower temperatures increased the SMP concentration and the relative abundance of Proteobacteria (including Zoogloea, the most dominant phylum and genus, relative abundance from 15.7 % to 61.1 %) while decreasing fluorescent EPS components, indicating the key role of Proteobacteria in SMP production and fluorescent EPS-to-SMP transformation. The results provided key insights into how changes in operational/environmental parameters impact sludge-EPS-SMP interactions, which could benefit the model development and operational optimization of activated sludge systems. This study also highlighted the important role of the sludge community in the EPS/SMP dynamics.

Regional citrate anticoagulation versus LMWH anticoagulation for CRRT in liver failure patients without increased bleeding risk.

BACKGROUND: The optimal anticoagulation regimen for continuous renal replacement therapy (CRRT) in liver failure (LF) patients without increased bleeding risk remains controversial. Therefore, we conducted a monocentric retrospective study to evaluate the efficacy and safety of the regional citrate anticoagulation (RCA) versus low molecular weight heparin (LMWH) anticoagulation for CRRT in LF without increased bleeding risk. METHOD: According to the anticoagulation strategy for CRRT, patients were divided into the RCA and LMWH-anticoagulation groups. The evaluated endpoints were patient survival, filter lifespan, bleeding, citrate accumulation, and totCa/ionCa ratio. RESULT: Totally 167 and 164 filters were used in the RCA and LMWH group, respectively. The median filter lifespan was significantly longer in the RCA group (34 h (IQR = 24-54) versus 24 h (IQR = 18-45.5) [95%CI, 24.5-33]; p < 0.001). The 4-week mortality rate was significantly higher in the LMWH-anticoagulation group (71 (57.72%) vs 53 (40.46%); p = 0.006). After adjusted the important parameters in the multivariate COX regression model, the mortality risk was significantly reduced in the RCA group (HR = 0.668 [95%CI, 0.468-0.955]; p = 0.027). In the LMWH group, 30 bleeding episodes (24,19%) were observed, whereas only 7 (5.34%) occurred in the RCA group (p < 0.001). Two patients (1.5%) in the RCA group occurred citrate accumulation. CONCLUSIONS: In LF patients without increased bleeding risk who underwent CRRT, RCA significantly extended the filter lifespan and improved patient survival rate. There was no significant difference in the rate of adverse events between the two groups.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

TRIM21-mediated ubiquitination of SQSTM1/p62 abolishes its Ser403 phosphorylation and enhances palmitic acid cytotoxicity.

Long-chain free fatty acids (FFAs) accumulation and oxidative toxicity is a major cause for several pathological conditions. The mechanisms underlying FFA cytotoxicity remain elusive. Here we show that palmitic acid (PA), the most abundant FFA in the circulation, induces S403 phosphorylation of SQSTM1/p62 (sequestosome 1) and its aggregation, which sequesters KEAP1 and activates the non-canonical SQSTM1-KEAP1-NFE2L2 antioxidant pathway. The PA-induced SQSTM1 S403 phosphorylation and aggregation are dependent on SQSTM1 K7-D69 hydrogen bond formation and dimerization in the Phox and Bem1 (PB1) domain, which facilitates the recruitment of TBK1 that phosphorylates SQSTM1 S403. The ubiquitin E3 ligase TRIM21 ubiquitinates SQSTM1 at the K7 residue and abolishes the PB1 dimerization, S403 phosphorylation, and SQSTM1 aggregation. TRIM21 is oxidized at C92, C111, and C114 to form disulfide bonds that lead to its oligomerization and decreased E3 activity. Mutagenizing the three C residues to S (3CS) abolishes TRIM21 oligomerization and increases its E3 activity. TRIM21 ablation leads to decreased SQSTM1 K7 ubiquitination, hence elevated SQSTM1 S403 phosphorylation and aggregation, which confers protection against PA-induced oxidative stress and cytotoxicity. Therefore, TRIM21 is a negative regulator of SQSTM1 phosphorylation, aggregation, and the antioxidant sequestration function. TRIM21 is oxidized to reduce its E3 activity that helps enhance the SQSTM1-KEAP1-NFE2L2 antioxidant pathway. Inhibition of TRIM21 May be a viable strategy to protect tissues from lipotoxicity resulting from long-chain FFAs.