E3 ubiquitin ligase BCA2 promotes breast cancer stemness by up-regulation of SOX9 by LPS.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Breast cancer stem cells (BCSCs) are believed to play a crucial role in the carcinogenesis, therapy resistance, and metastasis of TNBC. It is well known that inflammation promotes stemness. Several studies have identified breast cancer-associated gene 2 (BCA2) as a potential risk factor for breast cancer incidence and prognosis. However, whether and how BCA2 promotes BCSCs has not been elucidated. Here, we demonstrated that BCA2 specifically promotes lipopolysaccharide (LPS)-induced BCSCs through LPS induced SOX9 expression. BCA2 enhances the interaction between myeloid differentiation primary response protein 88 (MyD88) and Toll-like receptor 4 (TLR4) and inhibits the interaction of MyD88 with deubiquitinase OTUD4 in the LPS-mediated NF-κB signaling pathway. And SOX9, an NF-κB target gene, mediates BCA2's pro-stemness function in TNBC. Our findings provide new insights into the molecular mechanisms by which BCA2 promotes breast cancer and potential therapeutic targets for the treatment of breast cancer.

Parents' knowledge and attitudes towards extracorporeal membrane oxygenation and their post-traumatic stress symptoms.

This cross-sectional study, conducted between January 2020 and July 2023, aimed to assess the knowledge, attitude, and post-traumatic stress symptoms (PTSS) among parents with children undergoing extracorporeal membrane oxygenation (ECMO) treatment. Out of 201 valid questionnaires collected, the median knowledge score was 3.00, the mean attitude score was 27.00 ± 3.20, and the mean PTSS score was 3.50 ± 1.54. Logistic regression identified associations between PTSS and parents with lower education levels, particularly junior high school and high school/technical secondary school education, as well as those occupied as housewives. Structural equation modeling highlighted direct effects, such as the impact of residence on education, education on employment status, and associations between knowledge, attitude, PTSS, employment status, monthly income, and parental demographics. The findings indicated inadequate knowledge and suboptimal attitudes among parents, especially those with lower education levels, emphasizing the need for educational resources. Furthermore, addressing parental PTSS through psychosocial support and screening was deemed essential, providing valuable insights for tailored interventions in this context.

CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10.

Pancreatic ductal adenocarcinoma (PDAC), is characteristic by a heterogeneous tumor microenvironment and gene mutations, conveys a dismal prognosis and low response to chemotherapy and immunotherapy. Here, we found that checkpoint suppressor 1 (CHES1) served as a tumor repressor in PDAC and was associated with patient prognosis. Functional experiments indicated that CHES1 suppressed the proliferation and invasion of PDAC by modulating cellular senescence. To further identify the downstream factor of CHES1 in PDAC, label-free quantitative proteomics analysis was conducted, which showed that the oncogenic Aldo-keto reductase 1B10 (AKR1B10) was transcriptionally repressed by CHES1 in PDAC. And AKR1B10 facilitated the malignant activity and repressed senescent phenotype of PDAC cells. Moreover, pharmaceutical inhibition of AKR1B10 with Oleanolic acid (OA) significantly induced tumor regression and sensitized PDAC cells to gemcitabine, and this combined therapy did not cause obvious side effects. Rescued experiments revealed that CHES1 regulated the tumorigenesis and gemcitabine sensitivity through AKR1B10-mediated senescence in PDAC. In summary, this study revealed that the CHES1/AKR1B10 axis modulated the progression and cellular senescence in PDAC, which might provide revenues for drug-targeting and senescence-inducing therapies for PDAC.

Case report: A case of anti-glycine receptor encephalomyelitis triggered by post-transplant or COVID-19 infection?

Even though long-term immunosuppressant drugs (ISD) are employed to inhibit immune system activity, enhancing graft functionality and patient survival in solid organ transplantation (SOT), these transplants often lead to immune complications, with post-transplant autoimmune diseases of the central nervous system (CNS) being uncommon. Here, we detail the case of a 66-year-old woman who underwent a renal transplantation 8 months prior, who was admitted with subacute onset of encephalomyelitis, accompanied by headaches, paraplegia, weakness, vomiting, and abdominal pain, with a positive COVID-19 nasopharyngeal swab test 1 month before admission. MRI scans of the brain revealed multiple lesions in the white matter of the bilateral deep frontal lobe, the left temporal lobe and insula lobe. Additionally, there were multiple short segment lesions in the spinal cord and subdural hematoma at T1, T6-T7 posterior. The serum revealed a positive result for GlyR-IgG. Following the administration of corticosteroid and intravenous immunoglobulin, there was a significant improvement in the patient's symptoms within 2 weeks, and her brain MRI showed a reduction in the lesion. Despite its rarity, we believe this to be the inaugural documentation of anti-GlyR encephalomyelitis occurring during renal transplantation. A full panel of antibodies for autoimmune encephalomyelitis is the key leading to the diagnosis.

USP3: Key deubiquitylation enzyme in human diseases.

Ubiquitination and deubiquitylation are pivotal posttranslational modifications essential for regulating cellular protein homeostasis and are implicated in the development of human diseases. Ubiquitin-specific protease 3 (USP3), a member of the ubiquitin-specific protease family, serves as a key deubiquitylation enzyme, playing a critical role in diverse cellular processes including the DNA damage response, cell cycle regulation, carcinogenesis, tumor cell proliferation, migration, and invasion. Despite notable research efforts, our current understanding of the intricate and context-dependent regulatory networks governing USP3 remains incomplete. This review aims to comprehensively synthesize existing published works on USP3, elucidating its multifaceted roles, functions, and regulatory mechanisms, while offering insights for future investigations. By delving into the complexities of USP3, this review strives to provide a foundation for a more nuanced understanding of its specific roles in various cellular processes. Furthermore, the exploration of USP3's regulatory networks may uncover novel therapeutic strategies targeting this enzyme in diverse human diseases, thereby holding promising clinical implications. Overall, an in-depth comprehension of USP3's functions and regulatory pathways is crucial for advancing our knowledge and developing targeted therapeutic approaches for human diseases.

The effects of environmental factors on the synthesis of water-soluble Monascus red pigments via submerged fermentation: a review.

Monascus pigments (MPs) have been used as natural food pigments for many years. There is a high demand for Monascus red pigments (MRPs) to enhance color and for antibacterial and cancer prevention therapies in food and medicine. Most MRPs are not water soluble, and the yield of water-soluble MRPs is naturally low. On the other hand, water-soluble MRP is more cost effective for application in industrial mass production. Therefore, it is important to improve the yield of water-soluble MRPs. Environmental factors have a significant influence on the synthesis of water-soluble MRPs, which is crucial for the development of industrial production of water-soluble MRPs. This review introduces the biosynthetic pathways of water-soluble MRPs and summarizes the effects of environmental factors on the yield of water-soluble MRPs. Acetyl coenzyme A (acetyl-CoA) is a precursor for MPs synthesis. Carbon and nitrogen sources and the carbon/nitrogen ratio can impact MP production by regulating the metabolic pathway of acetyl-CoA. Optimization of fermentation conditions to change the morphology of Monascus can stimulate the synthesis of MPs. The appropriate choice of nitrogen sources and pH values can promote the synthesis of MRPs from MPs. Additives such as metal ions and non-ionic surfactants can affect the fluidity of Monascus cell membrane and promote the transformation of MRPs into water-soluble MRPs. This review will lay the foundation for the industrial production of water-soluble MRPs. © 2024 Society of Chemical Industry.

Vascularized fascial flap for reconstruction of combined oral mucosa-mandibular defects: The multi-modal biological assessment.

OBJECTIVE: The reconstruction of composite defects in the oral and maxillofacial region using vascularized fascial flaps, such as the fibular, iliac, and temporal fascial flaps, has gained increasing attention among surgeons. However, there remains uncertainty regarding the suitability of fascial flaps as transplants, as well as their healing processes and outcomes, due to their non-mucosal nature. This study aims to comprehensively assess the biological aspects of vascularized fascial flaps at clinical, histological, and genetic levels, with the goal of providing essential biological references for their clinical application. STUDY DESIGN: This study enrolled three patients who underwent reconstruction of combined oral mucosa-mandibular defects using fibular vascularized fascial flaps between 2020 and 2023. Data regarding changes in the appearance of the fascial flaps, bulk-RNA sequencing, and histological slices of initial fascia, initial gingiva, and transformed fascia were collected and analyzed. RESULTS: Within three months, the fascial flaps exhibited rapid epithelial coverage and displayed distinct characteristics resembling mucosa. High-throughput RNA sequencing analyses and histological slices revealed that the transformed fascia exhibited tissue structures similar to mucosa and demonstrated unique advantages in promoting blood vessel formation and reducing scarring through the high-level expression of relevant genes. CONCLUSION: These findings emphasize the potential and feasibility of utilizing vascularized fascial flaps for oral mucosa reconstruction, establishing their unique advantage as transplant materials, and providing significant biological information and references for their selection and clinical application.

Artificial kagome lattices of Shockley surface states patterned by halogen hydrogen-bonded organic frameworks.

Artificial electronic kagome lattices may emerge from electronic potential landscapes using customized structures with exotic supersymmetries, benefiting from the confinement of Shockley surface-state electrons on coinage metals, which offers a flexible approach to realizing intriguing quantum phases of matter that are highly desired but scarce in available kagome materials. Here, we devise a general strategy to construct varieties of electronic kagome lattices by utilizing the on-surface synthesis of halogen hydrogen-bonded organic frameworks (XHOFs). As a proof of concept, we demonstrate three XHOFs on Ag(111) and Au(111) surfaces, which correspondingly deliver regular, breathing, and chiral breathing diatomic-kagome lattices with patterned potential landscapes, showing evident topological edge states at the interfaces. The combination of scanning tunnelling microscopy and noncontact atomic force microscopy, complemented by density functional theory and tight-binding calculations, directly substantiates our method as a reliable and effective way to achieve electronic kagome lattices for engineering quantum states.

Copper-Catalyzed Domino-Double Annulation of o-Aminobenzamides with 2-Iodoisothiocyanates for the Synthesis of 12H-Benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones.

A facile and efficient copper-catalyzed domino-double annulation strategy was developed from easily accessible o-aminobenzamides and 2-iodoisothiocyanates, which affords a direct pathway for the synthesis of tetracyclic fused 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones in moderate to good yields without the addition of ligands, bases, and external oxidants. The reaction involves a C-N bond cleavage and the formation of a C-N/C-S bond in one step with the advantages of using an inexpensive copper catalyst and easy operation. Mechanistic studies suggest that this transformation proceeds via intermolecular condensation of o-aminobenzamides with 2-iodoisothiocyanates, followed by an intramolecular Ullmann-type cross-coupling cyclization reaction.

Association between polycyclic aromatic hydrocarbons and infertility in U.S. women: National Health and Nutrition Examination Survey 2013-2016.

Although there is a body of research indicating the potential impact of polycyclic aromatic hydrocarbons (PAHs) exposure on male infertility, the understanding of how PAH might affect female infertility is still limited. This study aimed to evaluate associations of PAHs, both individually and as a mixture, with female infertility using multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC) models based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. The study included 729 female participants. Multiple logistic regression results indicated that there was a significant association between the third tertile of 2-hydroxy fluorene (2-OHFLU) and female infertility, and the OR was 2.84 (95% CI: 1.24-6.53, P value = 0.015) compared with the first tertile after adjusting for the potential covariates. The BKMR model revealed a positive overall trend between mixed PAH exposure and female infertility, particularly when the mixture was at or above the 55th percentile, where 2-hydroxynaphthalene (2-OHNAP) and 1-hydroxypyrene (1-OHPYR) were the primary influences of the mixture. The univariate exposure-response function indicated positive associations between individual PAH exposure, specifically 2-OHNAP, 2-OHFLU, and 1-OHPYR, and female infertility. The QGC model also indicated a positive trend between exposure to a mixture of PAHs and female infertility, although it did not reach statistical significance (OR = 1.33, 95%CI: 0.86-2.07), with 1-OHPYR having the greatest positive effect on the outcome. This study suggested that exposure to PAHs may be associated with female infertility and further research is needed to consolidate and confirm these findings.

Immune Epitopes of SARS-CoV-2 Spike Protein and Considerations for Universal Vaccine Development.

Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and virus immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination in humans. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the TLRs, B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.

Two-Dimensional Spin-Crossover Molecular Solid Solutions with Tunable Transition Temperatures across 90 K.

Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.

Systems genetics analysis reveals the common genetic basis for pain sensitivity and cognitive function.

BACKGROUND: There is growing evidence of a strong correlation between pain sensitivity and cognitive function under both physiological and pathological conditions. However, the detailed mechanisms remain largely unknown. In the current study, we sought to explore candidate genes and common molecular mechanisms underlying pain sensitivity and cognitive function with a transcriptome-wide association study using recombinant inbred mice from the BXD family. METHODS: The pain sensitivity determined by Hargreaves' paw withdrawal test and cognition-related phenotypes were systematically analyzed in 60 strains of BXD mice and correlated with hippocampus transcriptomes, followed by quantitative trait locus (QTL) mapping and systems genetics analysis. RESULTS: The pain sensitivity showed significant variability across the BXD strains and co-varies with cognitive traits. Pain sensitivity correlated hippocampual genes showed a significant involvement in cognition-related pathways, including glutamatergic synapse, and PI3K-Akt signaling pathway. Moreover, QTL mapping identified a genomic region on chromosome 4, potentially regulating the variation of pain sensitivity. Integrative analysis of expression QTL mapping, correlation analysis, and Bayesian network modeling identified Ring finger protein 20 (Rnf20) as the best candidate. Further pathway analysis indicated that Rnf20 may regulate the expression of pain sensitivity and cognitive function through the PI3K-Akt signaling pathway, particularly through interactions with genes Ppp2r2b, Ppp2r5c, Col9a3, Met, Rps6, Tnc, and Kras. CONCLUSIONS: Our study demonstrated that pain sensitivity is associated with genetic background and Rnf20-mediated PI3K-Akt signaling may involve in the regulation of pain sensitivity and cognitive functions.

Escherichia coli and HPV16 coinfection may contribute to the development of cervical cancer.

Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli's coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Exogenous γ-Aminobutyric Acid (GABA) Enhanced Response to Abiotic Stress in Hypsizygus marmoreus by Improving Mycelial Growth and Antioxidant Capacity.

γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses.

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population.

AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.

Fast needling combined with occupational therapy for hand dysfunction of spastic cerebral palsy : a randomized controlled trial. / å¿«é’ˆç»“åˆä½œä¸šç–—æ³•æ²»ç–—ç—‰æŒ›åž‹è„‘ç˜«æ‚£å„¿æ‰‹åŠŸèƒ½éšœç¢ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the clinical effect of fast needling (without needle retaining), needle retaining acupuncture combined with occupational therapy and simple occupational therapy for hand dysfunction of spastic cerebral palsy in children. METHODS: A total of 75 children with spastic cerebral palsy were randomly divided into an occupational therapy group (25 cases), a fast needling group (25 cases, 1 case dropped out) and a needle retaining group (25 cases, 1 case dropped out). The patients in the occupational therapy group were only treated with occupational therapy for 20 min each time. The patients in the fast needling group were treated with acupuncture (without needle retaining) combined with occupational therapy, and the needle retaining group was treated with acupuncture (needle retaining) combined with occupational therapy, and acupuncture was taken at Hegu (LI 4), Houxi (SI 3), Yuji (LU 10), Waiguan (SJ 5), Jianyu (LI 15) and so on. The needles were retained for 30 min in patients of the needle retaining group. All the above treatments were performed once a day, 5 times a week for 12 weeks. The scores of fine motor function measure (FMFM) and Peabody developmental motor scale 2 (PDMS-2) were observed in patients of the three groups before and after treatment, and the safety of the fast needling group and the needle retaining group was compared. RESULTS: After treatment, the scores of FMFM and PDMS-2 in patients of the three groups were higher than those before treatment (P<0.01), and the scores of FMFM and PDMS-2 in the fast needling group and the needle retaining group were higher than those in the occupational therapy group (P<0.05, P<0.01). The incidence of acupuncture abnormalities in the fast needling group was 0.3% (5/1 440), which was lower than 1.4% (20/1 440) in the needle retaining group (P<0.05). CONCLUSIONS: Acupuncture combined with occupational therapy has better clinical effect than occupational therapy alone in improving hand dysfunction in children with spastic cerebral palsy, and there is no statistical difference in effect between fast needling acupuncture and needle retaining acupuncture, but fast needling has better safety than needle retaining acupuncture.

[Serological Characteristics and Clinical Significance of Irregular Antibodies in Pregnant Women].

OBJECTIVE: To understand the serological characteristics of irregular antibodies in pregnant women and explore their clinical significance. METHODS: From January 2017 to March 2022, 151 471 pregnant women in Women and Children's Hospital of Chongqing Medical University were enrolled in this study, microcolumn gel card test was used for irregular antibody screening, and antibody specificity identification was further performed in some antibody-positive subjects. RESULTS: The positive rate of irregular antibody screening in the enrolled pregnant women was 0.91% (1 375/151 471), 0.23% (355/151 471) was detected in the first trimester, 0.05% (71/151 471) in the second trimester, and 0.63% (949/151 471) in the third trimester. The positive rate of irregular antibody screening in the third trimester was significantly higher than that in the first and second trimester, and a significant increase in the number of positive cases was found in the third trimester than that in the second trimester. The analysis of agglutination intensity of 1 375 irregular antibody screening positive results showed that the weakly positive agglutination intensity accounted for 50.11% (689/ 1 375), which was the highest, the suspicious positive was 18.69% (257/1 375), and the positive was 31.20% (429/1 375). The significant difference in distribution of agglutination intensity was not observed between the first trimester group and the second trimester group, however, in the third trimester, the proportion of suspicious positive and weakly positive was lower than the first trimester, while, the proportion of positive was higher than the first trimester, and the difference was statistically significant (P < 0.001). Among the irregular antibody screening positive pregnant women, the proportion of pregnant women with pregnancy number ≥ 2 was significantly higher than that with pregnancy ≤ 1. Among 60 pregnant women who underwent antibody identification, the distributions of the antibodies were as follows: Rh blood group system accounted for 23.33% (14/60), Lewis system 43.33% (26/60), Kidd system 3.33% (2/60), MNS system 16.67% (10/60), P1PK system 1.67% (1/60), autoantibodies 1.67% (1/60), and 4 cases was unable to identify (6.67%, 4/60). Among specific antibodies, the anti-Lea was the most common (30.00%), followed by anti-E (16.67%) and anti-M (16.67%). CONCLUSION: The differences of irregular antibody serological characteristics exist in pregnant women from different regions with different genetic backgrounds, understanding the characteristics of irregular antibody in local pregnant women is of great significance for ensuring transfusion safety in pregnant women and preventing hemolytic disease of newborn.

Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases. METHODS: We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties. Flow cytometry examined the drug's impact on brain microglia. TNF-α, IL-1ß, and IL-6 levels in hippocampal tissue were assessed using ELISA kits. RESULTS: Roflumilast improved motor dysfunction and depression symptoms in EAE rats. Histopathological analysis revealed reduced inflammation, demyelination, and axonal loss in the spinal cord. Roflumilast suppressed microglial cell activation and conversion to pro-inflammatory M1-type cells. Flow cytometry showed roflumilast inhibited inflammatory marker expression in microglia and their activation in the hippocampus. IL-6 was identified as a roflumilast target for suppressing hippocampal inflammation. LIMITATIONS: This study used an animal model and did not assess long-term or potential side effects of roflumilast treatment. CONCLUSIONS: Roflumilast holds promise as a treatment for depression and motor impairment in MS. Its anti-inflammatory properties, reducing inflammation and inhibiting microglial activation, suggest its potential for MS therapy. However, further research is needed to evaluate long-term effects and safety in MS patients.

Association between phthalates and sleep problems in the U.S. adult females from NHANES 2011-2014.

There is little research on the relationship between phthalates exposure and sleep problems in adult females, with existing studies only assessing the association between exposure to individual phthalates with sleep problems. We aimed to analyse the relationship between phthalates and sleep problems in 1366 US females aged 20 years and older from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) by age stratification. Multivariate logistic regression showed that the fourth quartile of MECPP increased the risk of sleep problems in females aged 20-39 compared with the reference quartile (OR: 1.87, 95% CI: 1.14, 3.08). The WQS index was significantly associated with the sleep problems in females aged 20-39. In the BKMR, a positive overall trend between the mixture and sleep problems in females aged 20-39. In this study, we concluded that phthalates might increase the risk of sleep problems in females aged 20-39.