Evidence of nitrogen inputs affecting soil nitrogen purification by mediating root exudates of salt marsh plants.

Salt marsh has an important 'purification' role in coastal ecosystems by removing excess nitrogen that could otherwise harm aquatic life and reduce water quality. Recent studies suggest that salt marsh root exudates might be the 'control centre' for nitrogen transformation, but empirical evidence is lacking. Here we sought to estimate the direction and magnitude of nitrogen purification by salt marsh root exudates and gain a mechanistic understanding of the biogeochemical transformation pathway(s). To achieve this, we used a laboratory incubation to quantify both the root exudates and soil nitrogen purification rates, in addition to the enzyme activities and functional genes under Phragmites australis populations with different nitrogen forms addition (NO3-, NH4+ and urea). We found that NO3- and urea addition significantly stimulate P. australis root exudation of total acids, amino acids, total sugars and total organic carbon, while NH4+ addition only significantly increased total acids, amino acids and total phenol exudation. High total sugars, amino acids and total organic carbon concentrations enlarged nitrogen purification potential by stimulating the nitrogen purifying bacterial activities (including enzyme activities and related genes expression). Potential denitrification rates were not significantly elevated under NH4+ addition in comparison to NO3- and urea addition, which should be ascribed to total phenol self-toxicity and selective inhibition. Further, urea addition stimulated urease and protease activities with providing more NH4+ and NO2- substrates for elevated anaerobic ammonium oxidation rates among the nitrogen addition treatments. Overall, this study revealed that exogenous nitrogen could increase the nitrogen purification-associated bacterial activity through accelerating the root exudate release, which could stimulate the activity of nitrogen transformation, and then improve the nitrogen removal capacity in salt marsh.

A single-cell sequence analysis of mouse subcutaneous white adipose tissue reveals dynamic changes during weaning.

Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFß ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.

Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway.

The luminal-to-basal transition in mammary epithelial cells (MECs) is accompanied by changes in epithelial cell lineage plasticity; however, the underlying mechanism remains elusive. Here, we report that deficiency of Frmd3 inhibits mammary gland lineage development and induces stemness of MECs, subsequently leading to the occurrence of triple-negative breast cancer. Loss of Frmd3 in PyMT mice results in a luminal-to-basal transition phenotype. Single-cell RNA sequencing of MECs indicated that knockout of Frmd3 inhibits the Notch signaling pathway. Mechanistically, FERM domain-containing protein 3 (FRMD3) promotes the degradation of Disheveled-2 by disrupting its interaction with deubiquitinase USP9x. FRMD3 also interrupts the interaction of Disheveled-2 with CK1, FOXK1/2, and NICD and decreases Disheveled-2 phosphorylation and nuclear localization, thereby impairing Notch-dependent luminal epithelial lineage plasticity in MECs. A low level of FRMD3 predicts poor outcomes for breast cancer patients. Together, we demonstrated that FRMD3 is a tumor suppressor that functions as an endogenous activator of the Notch signaling pathway, facilitating the basal-to-luminal transformation in MECs.

Correlation Analysis of Apparent Diffusion Coefficient Histogram Parameters and Clinicopathologic Features for Prognosis Prediction in Uveal Melanoma.

Purpose: To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis. Methods: This retrospective study included 53 patients with UM who underwent diffusion-weighted imaging (DWI) between August 2015 and March 2024. Axial DWI was performed with a single-shot spin-echo echo-planar imaging sequence. ADC histogram parameters of ADCmean, ADC50%, interquartile range (IQR), skewness, kurtosis, and entropy were obtained from DWI. The relationships between histogram parameters and high-risk clinicopathological characteristics including tumor size, preoperative retinal detachment, histological subtypes, Ki-67 index, and chromosome status, were analyzed by Spearman correlation analysis, Mann-Whitney U test, or Kruskal-Wallis test. Results: A total of 53 patients (mean ± SD age, 55 ± 15 years; 22 men) were evaluated. The largest basal diameter (LBD) was correlated with kurtosis (r = 0.311, P = 0.024). Tumor prominence (TP) was correlated with entropy (r = 0.581, P < 0.001) and kurtosis (r = 0.273, P = 0.048). Additionally, significant correlations were identified between the Ki-67 index and ADCmean (r = -0.444, P = 0.005), ADC50% (r = -0.487, P = 0.002), and skewness (r = 0.394, P = 0.014). Finally, entropy was correlated with monosomy 3 (r = 0.541, P = 0.017). Conclusions: The ADC histograms provided valuable insights into high-risk clinicopathologic features of UM and hold promise in the early prediction of UM prognosis.

Sex-related differences in left atrial substrate among patients with atrial fibrillation: evidence from high-density voltage mapping.

BACKGROUND: There is sufficient evidence that women with atrial fibrillation (AF) have a greater symptom burden than men with AF and are more likely to experience recurrence after catheter ablation. However, the mechanisms underlying these sex differences are unclear. METHODS: We prospectively enrolled 125 consecutive patients, including 40 non-AF patients and 85 AF patients, who underwent high-density voltage mapping during sinus rhythm and AF patients who underwent first ablation. RESULTS: Overall, 37 (44%) female patients with AF and 24 (60%) female non-AF patients with a mean age of 61.7 ± 11.6 years and 53.6 ± 16.7 years, respectively, were enrolled in this study. The results showed that the atrial voltage of female AF patients was significantly lower than that of male AF patients (1.11 ± 0.58 mV vs. 1.53 ± 0.65 mV; P = 0.003), while there were no significant sex differences in non-AF patients (3.02 ± 0.86 mV vs. 3.21 ± 0.84 mV; P = 0.498). Multiple linear regression analysis revealed that female sex (- 0.29, 95% confidence interval [CI] - 0.64 to - 0.13, P = 0.004) and AF type (- 0.32, 95% CI - 0.69 to - 0.13, P = 0.004) were the only factors independently associated with voltage. Compared with men, women in the paroxysmal AF group had a 3.5-fold greater incidence of recurrence (adjusted hazard ratio 4.49; 95% CI 1.101-18.332, P = 0.036). Both globally and regionally, the results showed that sex-related differences in voltage values occurred prominently in paroxysmal AF patients but not in nonparoxysmal AF patients. CONCLUSION: Sex-related differences in atrial substrates and arrhythmia-free survival were found in paroxysmal AF patients, suggesting the existence of sex-related pathophysiological factors.

An ionically cross-linked composite hydrogel electrolyte based on natural biomacromolecules for sustainable zinc-ion batteries.

Zinc-ion batteries (ZIBs) are regarded as promising power sources for flexible and biocompatible devices due to their good sustainability and high intrinsic safety. However, their applications have been hindered by the issues of uncontrolled Zn dendrite growth and severe water-induced side reactions in conventional liquid electrolytes. Herein, an ionically cross-linked composite hydrogel electrolyte based on natural biomacromolecules, including iota-carrageenan and sodium alginate, is designed to promote highly efficient and reversible Zn plating/stripping. The abundant functional groups of macromolecules effectively suppress the reactivity of water molecules and facilitate uniform Zn deposition. Moreover, the composite hydrogel electrolyte exhibits a high ionic conductivity of 5.89 × 10-2 S cm-1 and a Zn2+ transference number of 0.58. Consequently, the Zn‖Zn symmetric cell with the composite hydrogel electrolyte shows a stable cycle life of more than 500 h. Meanwhile, the Zn‖NH4V4O10 coin cell with the composite hydrogel electrolyte retains a high specific capacity of approximately 200 mA h g-1 after 600 cycles at 2 A g-1. The Zn‖NVO pouch cell based on the composite hydrogel electrolyte also shows a high specific capacity of 246.1 mA h g-1 at 0.5 A g-1 and retains 70.7% of its initial capacity after 150 cycles. The pouch cell performs well at different bending angles and exhibits a capacity retention rate of 98% after returning to its initial state from 180° folding. This work aims to construct high-performance hydrogel electrolytes using low-cost natural materials, which may provide a solution for the application of ZIBs in flexible biocompatible devices.

Comparative SEM Study of Sensilla and Tyloid Structures in the Antennae of Vespinae (Hymenoptera: Vespidae).

This study investigates the distribution, morphology, and potential functions of antennal sensilla in various wasp species, including Dolichovespula flora, D. intermedia, Vespula structor, Vl. vulgaris, Provespa barthelemyi, Vespa bicolor, V. ducalis, V. mocsaryana, and V. velutina var. nigothorax. The study thoroughly analyzes the antennal structure of these species, representing all four genera of the yellow-jacket and hornet subfamily Vespinae. Using scanning electron microscopy (SEM), the study identifies a total of nineteen types of sensilla, including sensilla trichodea (ST-I, ST-II, ST-III), sensilla campaniform (SCF-I, SCF-II, SCF-III), pit organs (SCO-I, SCO-II, and SA), sensilla placodea (SP-I, SP-II), sensilla chaetica (SCH-I, SCH-II), sensilla basiconica (SB-I, SB-II), sensilla agmon (SAG-I, SAG-II), and sensilla coelocapitular (SCA). Additionally, tyloids were observed in the males of seven species, except for Vl. structor and Vl. vulgaris. The study provides insights into these sensilla types' morphology, abundance, and distribution. It discusses the variations in sensilla morphology among different species and the presence of gender-specific sensilla. This study provides new data about the morphology and distribution patterns of sensilla and tyloid.

Establishment of a microspheres-based homogeneous fluorescence immunoassay for the rapid detection of cardiac troponin I.

Myocardial infarction occurs rapidly, and thus the rapid detection of cTnI levels is the key to its diagnosis. Most current assays take 10-30 min. In this study, we developed a method for accurately measuring cardiac troponin I (cTnI) levels in human sera with amplified luminescence neighborhood homogeneous assay (AlphaLISA). The method involves coupling two cTnI antibodies targeting different epitopes to the surface of carboxylated donor and acceptor beads. The final signal values were detected by the double-antibody sandwich method, and the best reaction conditions were obtained by optimizing the experimental conditions. The sensitivity, specificity, accuracy, and precision of the method were evaluated. Results showed that the method requires only 3 min to produce the results, the detection sensitivity is 27.06 ng L-1, and the measurement range is 34.56-62 500 ng L-1. cTnI-AlphaLISA has an intra-assay precision of 2.18-4.57% (<10%) and an inter-assay precision of 5.60-6.95% (<10%). The relative recovery rates are within reasonable limits. In addition, the serum assay results of the method were compared with chemiluminescence immunoassay, and the results are in agreement with one another (ρ = 0.8803; P < 0.0001). The method is expected to be developed as a routine method, but further studies and evaluations are needed.

Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

The N-glycosylation at positions 652 and 661 of viral spike protein negatively modulates porcine deltacoronavirus entry.

N-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of N-glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of N-glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that N-glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of N-glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.

Highly Stable Beneficiary Attribution in Medicare's Comprehensive Primary Care Plus Model.

BACKGROUND: Advanced primary care models are key in moving primary care practices toward greater accountability for the quality and cost of a beneficiary's care. One critical but often overlooked detail in model design is the beneficiary attribution methodology. Attribution results are key inputs in calculating practice payments. Stable attribution yields predictable practice payments, fostering longer-term investments in advanced primary care. OBJECTIVE: We examine attribution stability for Medicare fee-for-service beneficiaries in Medicare's Comprehensive Primary Care Plus (CPC+) Model. DESIGN: To measure attribution stability, we calculate churn rates, which we define as the percentage of beneficiaries eligible for CPC+ who were not attributed to the same practice in a later period. Using 2017-2021 CPC+ program data and Medicare administrative data, we calculate churn rates for CPC+ overall and for beneficiary subgroups. To assess whether CPC+ attribution was responsive enough to changes in a beneficiary's practice, we calculate how long before attribution changes following a beneficiary's long-distance move. RESULTS: We find that for every 100 beneficiaries attributed to a CPC+ practice, 88 were still attributed to the same practice a year later (ie, churn rate of 12%), 79 were attributed 2 years later, 74 three years later, and 70 four years later. However, some vulnerable subgroups, such as disabled beneficiaries, had higher churn rates. Our analysis of long-distance movers reveals that only after 5 quarters did attribution change for more than half of these movers. CONCLUSIONS: Overall, high attribution stability may have encouraged CPC+ practices to make longer-term investments in advanced primary care.

A new species of the genus Yoldiella (Bivalvia, Protobranchia, Yoldiidae) from Haima Cold Seep, South China Sea, China.

In present study, a previously unidentified but frequently encountered species of deep-sea protobranch, Yoldiellahaimaensis sp. nov., is described new to science from the Haima Cold Seep on the northwestern slope of the South China Sea. A morphological analysis confirmed that this species belongs to a previously undescribed species of the genus Yoldiella A.E. Verrill & K.J. Bush, 1897. It differs morphologically from other known species within the genus in its shell shape, degree of inflation, beaks, and number of hinge teeth. Furthermore, we sequenced three gene segments of Y.haimaensis sp. nov., comprising a nuclear ribosomal gene (18S rRNA), a nuclear protein-coding gene (histone H3), and a mitochondrial gene (cytochrome c oxidase subunit I, COI). Our phylogenetic analysis performed on the superfamily Nuculanoidea and family Yoldiidae indicates that the genus Yoldiella is non-monophyletic, and the widely recognized families within the superfamily Nuculanoidea are also not monophyletic. Our results provide molecular insights into the Protobranchia and highlight the necessity for further samples and data to revise the classification of families and genera within the superfamily using an integrative approach that combines morphological analysis and molecular data.

Investigating the Influence of Varied Light-Emitting Diode (LED) Wavelengths on Phototactic Behavior and Opsin Genes in Vespinae.

The phototactic behavior of insects is commonly used to manage pest populations in practical production. However, this elusive behavior is not yet fully understood. Investigating whether the opsin genes play a crucial role in phototaxis is an intriguing topic. Vespinae (Hymenoptera: Vespidae) are a common group of social wasps that are closely associated with human activities. Efficiently controlling wasp populations while maintaining ecological balance is a pressing global challenge that still has to be resolved. This research aims to explore the phototactic behavior and key opsin genes associated with Vespinae. We found significant differences in the photophilic rates of Vespula germanica and Vespa analis under 14 different light conditions, indicating that their phototactic behavior is rhythmic. The results also showed that the two species exhibited varying photophilic rates under different wavelengths of light, suggesting that light wavelength significantly affects their phototactic behavior. Additionally, the opsin genes of the most aggressive hornet, Vespa basalis, have been sequenced. There are only two opsin genes, one for UV light and the other for blue light, and Vespa basalis lacks long-wavelength visual proteins. However, they exhibit peak phototaxis for long-wavelength light and instead have the lowest phototaxis for UV light. This suggests that the visual protein genes have a complex regulatory mechanism for phototactic behavior in Vespinae. Additionally, visual protein sequences have a high degree of homology among Hymenoptera. Despite the hypotheses put forward by some scholars regarding phototaxis, a clear and complete explanation of insect phototaxis is still lacking to date. Our findings provide a strong theoretical basis for further investigation of visual expression patterns and phototactic mechanisms in Vespinae.

Intensive chemotherapy with dual induction and ALL-like consolidation for childhood acute myeloid leukemia: a respective report from multiple centers in China.

Background: Pediatric acute myeloid leukemia (AML) has poor prognosis and high rate of relapse and mortality, and exploration of new treatment options is still critically needed. Objectives: To summarize the outcome of our new treatment strategies for pediatric AML, which is characterized by dual induction and acute lymphoblastic leukemia (ALL) elements consolidation. Design: Retrospective, single-arm study. Methods: From July 2012 to December 2019, an intensive chemotherapy protocol was used for newly diagnosed children with AML, which contains dual induction, three courses of consolidations based on high-dose cytarabine, and two courses of consolidations composed of high-dose methotrexate, vincristine, asparaginase, and mercaptopurine (ALL-like elements). Blasts were monitored by bone marrow smears at intervals, and two lumbar punctures were performed during chemotherapy. We retrospectively analyzed the efficacy and safety of this study. The last follow-up was on 26 May 2023. Results: A total of 70 pediatric AMLs were included. The median age at diagnosis was 6.7 (0.5-16.0) years. The median initial WBC count was 23.74 × 109/L, 11 of whom ⩾100 × 109/L. After dual induction, there were 62 cases of complete remission (CR), 5 cases of partial remission, and 3 cases of nonremission. The CR rate was 88.57%. The median follow-up time was 5.8 (0.2-9.4) years, the 5-year overall survival was 78.2% ± 5%, the event-free survival (EFS) was 71.2% ± 5.6%, and the cumulative recurrence rate was 27.75%. The 5-year EFS of patients with initial WBC < 100 × 109/L (n = 59) and ⩾100 × 109/L (n = 11) were 76.4% ± 5.7% and 45.5% ± 15% (p = 0.013), respectively. A total of 650 hospital infections occurred. The main causes of infection were respiratory tract infection (26.92%), septicemia (18.46%), stomatitis (11.85%), and skin and soft-tissue infection (10.46%). Conclusion: This intensive treatment protocol with dual induction and ALL-like elements is effective and safe for childhood AML. Initial WBC ⩾ 100 × 109/L was the only independent risk factor in this cohort. Trial registration: It is a retrospective study, and no registration on ClinicalTrials.gov.

Characterization of metallothionein genes from Broussonetia papyrifera: metal binding and heavy metal tolerance mechanisms.

BACKGROUND: Broussonetia papyrifera is an economically significant tree with high utilization value, yet its cultivation is often constrained by soil contamination with heavy metals (HMs). Effective scientific cultivation management, which enhances the yield and quality of B. papyrifera, necessitates an understanding of its regulatory mechanisms in response to HM stress. RESULTS: Twelve Metallothionein (MT) genes were identified in B. papyrifera. Their open reading frames ranged from 186 to 372 bp, encoding proteins of 61 to 123 amino acids with molecular weights between 15,473.77 and 29,546.96 Da, and theoretical isoelectric points from 5.24 to 5.32. Phylogenetic analysis classified these BpMTs into three subclasses: MT1, MT2, and MT3, with MT2 containing seven members and MT3 only one. The expression of most BpMT genes was inducible by Cd, Mn, Cu, Zn, and abscisic acid (ABA) treatments, particularly BpMT2e, BpMT2d, BpMT2c, and BpMT1c, which showed significant responses and warrant further study. Yeast cells expressing these BpMT genes exhibited enhanced tolerance to Cd, Mn, Cu, and Zn stresses compared to control cells. Yeasts harboring BpMT1c, BpMT2e, and BpMT2d demonstrated higher accumulation of Cd, Cu, Mn, and Zn, suggesting a chelation and binding capacity of BpMTs towards HMs. Site-directed mutagenesis of cysteine (Cys) residues indicated that mutations in the C domain of type 1 BpMT led to increased sensitivity to HMs and reduced HM accumulation in yeast cells; While in type 2 BpMTs, the contribution of N and C domain to HMs' chelation possibly corelated to the quantity of Cys residues. CONCLUSION: The BpMT genes are crucial in responding to diverse HM stresses and are involved in ABA signaling. The Cys-rich domains of BpMTs are pivotal for HM tolerance and chelation. This study offers new insights into the structure-function relationships and metal-binding capabilities of type-1 and - 2 plant MTs, enhancing our understanding of their roles in plant adaptation to HM stresses.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

HBXIP induces PARP1 via WTAP-mediated m6A modification and CEBPA-activated transcription in cisplatin resistance to hepatoma.

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

Metabolomics-based study on the significance of differential metabolite binding IgG isoforms in Hemolytic disease of newborn.

BACKGROUND: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions. METHODS: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment. RESULTS: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN. CONCLUSION: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.