The RNA helicase DHX35 functions as a co-sensor for RIG-I-mediated innate immunity.

RNA helicases are involved in the innate immune response against pathogens, including bacteria and viruses; however, their mechanism in the human airway epithelial cells is still not fully understood. Here, we demonstrated that DEAH (Asp-Glu-Ala-His) box polypeptide 35 (DHX35), a member of the DExD/H (Asp-Glu-x-Asp/His)-box helicase family, boosts antiviral innate immunity in human airway epithelial cells. DHX35 knockdown attenuated the production of interferon-ß (IFN-ß), IL6, and CXCL10, whereas DHX35 overexpression increased their production. Upon stimulation, DHX35 was constitutively expressed, but it translocated from the nucleus into the cytosol, where it recognized cytosolic poly(I:C) and poly(dA:dT) via its HELICc domain. Mitochondrial antiviral signaling protein (MAVS) acted as an adaptor for DHX35 and interacted with the HELICc domain of DHX35 using amino acids 360-510. Interestingly, DHX35 interacted with retinoic acid-inducible gene 1 (RIG-I), enhanced the binding affinity of RIG-I with poly(I:C) and poly(dA:dT), and formed a signalsome with MAVS to activate interferon regulatory factor 3 (IRF3), NF-κB-p65, and MAPK signaling pathways. These results indicate that DHX35 not only acted as a cytosolic nucleic acid sensor but also synergized with RIG-I to enhance antiviral immunity in human airway epithelial cells. Our results demonstrate a novel molecular mechanism for DHX35 in RIG-I-mediated innate immunity and provide a novel candidate for drug and vaccine design to control viral infections in the human airway.

Proteomic Analysis Revealed the Potential Role of MAGE-D2 in the Therapeutic Targeting of Triple-Negative Breast Cancer.

Among all the molecular subtypes of breast cancer, triple-negative breast cancer (TNBC) is the most aggressive one. Currently, the clinical prognosis of TNBC is poor because there is still no effective therapeutic target. Here, we carried out a combined proteomic analysis involving bioinformatic analysis of the proteome database, label-free quantitative proteomics, and immunoprecipitation (IP) coupled with mass spectrometry (MS) to explore potential therapeutic targets for TNBC. The results of bioinformatic analysis showed an overexpression of MAGE-D2 (melanoma antigen family D2) in TNBC. In vivo and in vitro experiments revealed that MAGE-D2 overexpression could promote cell proliferation and metastasis. Furthermore, label-free quantitative proteomics revealed that MAGE-D2 acted as a cancer-promoting factor by activating the PI3K-AKT pathway. Moreover, the outcomes of IP-MS and cross-linking IP-MS demonstrated that MAGE-D2 could interact with Hsp70 and prevent Hsp70 degradation, but evidence for their direct interaction is still lacking. Nevertheless, MAGE-D2 is a potential therapeutic target for TNBC, and blocking MAGE-D2 may have important therapeutic implications.

Acyl carrier protein OsMTACP2 confers rice cold tolerance at the booting stage.

Low temperatures occurring at the booting stage in rice (Oryza sativa L.) often result in yield loss by impeding male reproductive development. However, the underlying mechanisms by which rice responds to cold at this stage remain largely unknown. Here, we identified MITOCHONDRIAL ACYL CARRIER PROTEIN 2 (OsMTACP2), the encoded protein of which mediates lipid metabolism involved in the cold response at the booting stage. Loss of OsMTACP2 function compromised cold tolerance, hindering anther cuticle and pollen wall development, resulting in abnormal anther morphology, lower pollen fertility, and seed setting. OsMTACP2 was highly expressed in tapetal cells and microspores during anther development, with the encoded protein localizing to both mitochondria and the cytoplasm. Comparative transcriptomic analysis revealed differential expression of genes related to lipid metabolism between the wild type and the Osmtacp2-1 mutant in response to cold. Through a lipidomic analysis, we demonstrated that wax esters, which are the primary lipid components of the anther cuticle and pollen walls, function as cold-responsive lipids. Their levels increased dramatically in the wild type but not in Osmtacp2-1 when exposed to cold. Additionally, mutants of two cold-induced genes of wax ester biosynthesis, ECERIFERUM1 and WAX CRYSTAL-SPARSE LEAF2, showed decreased cold tolerance. These results suggest that OsMTACP2-mediated wax ester biosynthesis is essential for cold tolerance in rice at the booting stage.

rTMS concurrent with cognitive training rewires AD brain by enhancing GM-WM functional connectivity: a preliminary study.

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40 Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.

WITHDRAWN: Investigating the ERG a-wave and Retinal Diseases with Rod Equivalent Circuit Model Based on the APD.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the Editor and Publisher, after being inadvertently published due to an editorial error. This error bears no reflection on the article or its authors. The Publisher apologizes for any inconvenience this may cause.

Quantitative Pattern of hPTMs by Mass Spectrometry-Based Proteomics with Implications for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is known for its aggressive nature, and TNBC management is currently challenging due to the lack of effective targets. Despite the importance of histone post-translational modifications (hPTMs) in breast cancer, their associations with molecular subtypes of breast cancer, especially TNBC, are poorly understood. In this study, a combination of untargeted and targeted proteomics approaches, supplemented by a derivatization method, was applied to breast cancer cells and tissue samples. Untargeted proteomics of eight breast cancer cell lines belonging to different molecular subtypes revealed 36 modified peptides with 12 lysine modification sites in histone H3, and the most frequently reported top 5 histone H3 methylation and acetylation sites were covered. Then, targeted proteomics was carried out to quantify the total 20 target hPTMs at the covered modification sites (i.e., mono-, di-, trimethylation, and acetylation for each site), indicating the difficulty in distinguishing TNBC cells from normal cells. Subsequently, the analysis in TNBC patients revealed significant expression differences in 4 specific hPTMs (H3K14ac, H3K27me1, H3K36me2, and H3K36me3) between TNBC and adjacent normal tissue samples. These unique hPTM patterns allowed for the differentiation of TNBC from normal cases. This finding provides promising implications for advancing targeted treatment strategies for TNBC in the future.

R-loop and diseases: the cell cycle matters.

The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.

Identification of the Electrogenerated Hidden Nitrenium Ions by In Situ Mass Spectrometry.

The identification of the electrogenerated reactive intermediates is essential for an in-depth understanding of the electroredox processes. Although various short-lived intermediates are well characterized by coupling electrochemistry with mass spectrometry (EC/MS), many electrogenerated transient species (τ < 1 µs) are still rarely captured by the currently available EC/MS approaches. Here, we present a low-delay coupling device, which was constructed by decorating a microelectrode into the front tip of a microsized ion emitter. For the first time, the in situ detection of a previously hidden intermediate, i.e., the transient nitrenium ion of carbazole (τ = 333 ns), was achieved. The electrochemical generation of indole nitrenium ion, whose half-life is estimated to be shorter compared to the carbazole nitrenium ion due to less resonance stabilization, was also confirmed by direct observation. This clog-free microelectrode/ion emitter is cheap and easy to fabricate and offers a general and powerful approach to monitoring the fast reactions of electrogenerated reactive intermediates. We believe that our integrated EC/MS approach holds substantial potential for broad applicability, particularly in probing the intricate and ultrafast electroredox processes occurring at the electrode-solution interface.

Rare Earth-Carbon Dots Nanocomposite-Modified Glass Nanopipettes: Electro-Optical Detection of Bacterial ppGpp.

As an important alarmone nucleotide, guanosine 3'-diphosphate-5'-diphosphate (ppGpp) can regulate the survival of bacteria under strict environmental conditions. Direct detection of ppGpp in bacteria with high sensitivity and selectivity is crucial for elucidating the role of ppGpp in bacterial stringent response. Herein, the terbium-carbon dots nanocomposite (CDs-Tb) modified glass nanopipet was developed for the recognition of ppGpp. The CDs-Tb in glass nanopipette preserved their fluorescence properties as well as the coordination capacity of Tb3+ toward ppGpp. The addition of ppGpp not only led to the fluorescence response of CDs-Tb but also triggered variations of surface charge inside the glass nanopipet, resulting in the ionic current response. Compared with nucleotides with similar structures, this method displayed good selectivity toward ppGpp. Moreover, the dual signals (fluorescence and ionic current) offered a built-in correction for potential interference. Apart from the high selectivity, the proposed method can determine the concentration of ppGpp from 10-13 to 10-7 M. Taking advantage of the significant analytical performance, we monitored ppGpp in Escherichia coli under different nutritional conditions and studied the relationship between ppGpp and DNA repair, which is helpful for overcoming antibiotic resistance and promoting the development of potential drugs for antibacterial treatment.

Constructing Ultra-Strong SERS Tags in the Cellular Raman-Silent Region by Orthogonal Array Testing Strategy.

Surface-enhanced Raman spectroscopy (SERS) tags have the advantages of unique fingerprint vibration spectrum, ultranarrow spectral line widths, and weak photobleaching effect, showing great potential for bioimaging. However, SERS imaging is still hindered for further application due to its weak spontaneous Raman scattering, biomolecular signal interference, and long acquisition times. Here, we develop a novel SERS tag of the core (Au)-shell (N-doped graphene) structure (Au@NGs) with ultrastrong and stable Raman signal (2180 cm-1) in the cellular Raman-silent region (1800-2800 cm-1) through base-promoted oxidative decarboxylation of amino acids. Exploring the factors (metal salts, amino acids, catalysts, temperature, etc.) to obtain Au@NGs with the strongest Raman signal commonly requires more than 100,000 separate experiments, while that using an orthogonal array testing strategy is reduced to 56. The existence of deep charge transfer between the Au surface and C≡N-graphene is proved by theoretical calculations, which means the ultrastrong signal of Au@NGs is the joint effect of electromagnetic and chemical enhancement. The Au@NGs have a detection sensitivity down to a single-nanoparticle level, and high-speed and high-resolution cellular imaging (4453 pixels) is obtained within 10 s by global Raman imaging. The combination of Au@NGs-based tags with ultrastrong intrinsic Raman imaging capability and global imaging technology holds great promise for high-speed Raman imaging.

Interleukin-10: a novel metabolic inducer of macrophage differentiation and subsequently contributing to improved pregnancy outcomes of mice by orchestrating oxidative phosphorylation metabolism†.

Metabolism regulates the phenotype and function of macrophages. After recruitment to local tissues, monocytes are influenced by the local microenvironment and differentiate into various macrophages depending on different metabolic pathways. However, the metabolic mechanisms underlying decidual macrophage differentiation remain unknown. Interleukin-10 (IL-10) is an important decidual macrophage inducer and promotes oxidative phosphorylation (OXPHOS) of bone marrow-derived macrophages. In this study, we mainly investigate the metabolic changes involved in IL-10-generated macrophages from monocytes using in vitro models. We demonstrate that exposure of monocytes (either peripheral or THP-1) to IL-10 altered the phenotype and function of resultant macrophages that are linked with OXPHOS changes. Interleukin-10 enhanced the mitochondrial complex I and III activity of THP-1 cell-differentiated macrophages and increased the mitochondrial membrane potential, intracellular adenosine triphosphate, and reactive oxygen species levels. Oxidative phosphorylation blockage with oligomycin changed the cell morphology of IL-10-generated macrophages and the expression levels of cytokines, such as transforming growth factor beta, tumor necrosis factor-alpha, interferon gamma, and IL-10, apart from changes in the expression level of the surface markers CD206, CD209, and CD163. Moreover, in vivo IL-10 administration reduced the lipopolysaccharide (LPS)-induced embryo resorption rate, and this effect was diminished when OXPHOS was inhibited, demonstrating that OXPHOS is important for the improved pregnancy outcomes of IL-10 in LPS-induced abortion-prone mice. Our findings provide deep insights into the roles of IL-10 in macrophage biology and pregnancy maintenance. Nevertheless, the direct evidence that OXPHOS is involved in decidual macrophage differentiation needs further investigations.

Natural variation in Fatty Acid 9 is a determinant of fatty acid and protein content.

Soybean is one of the most economically important crops worldwide and an important source of unsaturated fatty acids and protein for the human diet. Consumer demand for healthy fats and oils is increasing, and the global demand for vegetable oil is expected to double by 2050. Identification of key genes that regulate seed fatty acid content can facilitate molecular breeding of high-quality soybean varieties with enhanced fatty acid profiles. Here, we analysed the genetic architecture underlying variations in soybean seed fatty acid content using 547 accessions, including mainly landraces and cultivars from northeastern China. Through fatty acid profiling, genome re-sequencing, population genomics analyses, and GWAS, we identified a SEIPIN homologue at the FA9 locus as an important contributor to seed fatty acid content. Transgenic and multiomics analyses confirmed that FA9 was a key regulator of seed fatty acid content with pleiotropic effects on seed protein and seed size. We identified two major FA9 haplotypes in 1295 resequenced soybean accessions and assessed their phenotypic effects in a field planting of 424 accessions. Soybean accessions carrying FA9H2 had significantly higher total fatty acid contents and lower protein contents than those carrying FA9H1 . FA9H2 was absent in wild soybeans but present in 13% of landraces and 26% of cultivars, suggesting that it may have been selected during soybean post-domestication improvement. FA9 therefore represents a useful genetic resource for molecular breeding of high-quality soybean varieties with specific seed storage profiles.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Effects of Early Enteral to Parenteral Protein Ratios on Brain Volume and Somatic Growth in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate whether a higher proportion of enteral vs parenteral protein ratio (E:P ratio) in the first 28 days after birth is associated with increased brain volume and somatic growth in very low birth weight (VLBW; birth weight <1500 g) infants. STUDY DESIGN: This was a retrospective analysis of a subcohort of VLBW infants (n = 256, gestational age mean 28.07 [SD 2.17] weeks, birth weight 1038.80 [SD 262.95] grams) from the Cincinnati Infant Neurodevelopment Early Prediction Study, a regional prospective study of infants born at ≤32 weeks' gestation. Brain magnetic resonance imaging was obtained at term-equivalent age. Macronutrient intake and growth metrics for the first 28 days were collected retrospectively. The primary outcome was total brain tissue volume. The relationships between E:P ratio, total and regional brain tissue volumes, and somatic growth were analyzed by multivariable linear regression models; composite variables were used to adjust for potential confounders including pregnancy risk factors and initial severity of illness. RESULTS: Higher E:P ratio was associated with increased total brain tissue volume but was not associated with change in head circumference z score. In secondary analyses, higher E:P ratio was associated with increased weight velocity. There were no significant associations between E:P ratio and change in weight or length z scores or regional brain volumes. CONCLUSIONS: Higher E:P ratio in the first 28 days was positively associated with total brain volume and weight gain. Promoting the provision of enteral over parenteral protein may improve brain and somatic growth in VLBW infants.

Single-Cell RNA-Sequencing of Soybean Reveals Transcriptional Changes and Antiviral Functions of GmGSTU23 and GmGSTU24 in Response to Soybean Mosaic Virus.

Soybean mosaic virus (SMV) stands as a prominent and widespread threat to soybean (Glycine max L. Merr.), the foremost legume crop globally. Attaining a thorough comprehension of the alterations in the transcriptional network of soybeans in response to SMV infection is imperative for a profound insight into the mechanisms of viral pathogenicity and host resistance. In this investigation, we isolated 50 294 protoplasts from the newly developed leaves of soybean plants subjected to both SMV infection and mock inoculation. Subsequently, we utilized single-cell RNA sequencing (scRNA-seq) to construct the transcriptional landscape at a single-cell resolution. Nineteen distinct cell clusters were identified based on the transcriptomic profiles of scRNA-seq. The annotation of three cell types-epidermal cells, mesophyll cells, and vascular cells-was established based on the expression of orthologs to reported marker genes in Arabidopsis thaliana. The differentially expressed genes between the SMV- and mock-inoculated samples were analyzed for different cell types. Our investigation delved deeper into the tau class of glutathione S-transferases (GSTUs), known for their significant contributions to plant responses against abiotic and biotic stress. A total of 57 GSTU genes were identified by a thorough genome-wide investigation in the soybean genome G. max Wm82.a4.v1. Two specific candidates, GmGSTU23 and GmGSTU24, exhibited distinct upregulation in all three cell types in response to SMV infection, prompting their selection for further research. The transient overexpression of GmGSTU23 or GmGSTU24 in Nicotiana benthamiana resulted in the inhibition of SMV infection, indicating the antiviral function of soybean GSTU proteins.

Improved photosynthetic performance under unilateral weak light conditions in a wide-narrow-row intercropping system is associated with altered sugar transport.

Intercropping improves resource utilization. Under wide-narrow-row maize (Zea mays) intercropping, maize plants are subjected to weak unilateral illumination and exhibit high photosynthetic performance. However, the mechanism regulating photosynthesis under unilateral weak light remains unknown. We investigated the relationship between photosynthesis and sugar metabolism in maize under unilateral weak light. Our results showed that the net photosynthetic rate (Pn) of unshaded leaves increased as the level of shade on the other side increased. On the contrary, the concentration of sucrose and starch and the number of starch granules in the unshaded leaves decreased with increased shading due to the transfer of abundant C into the grains. However, sink loss with ear removal reduced the Pn of unshaded leaves. Intense unilateral shade (40% to 20% normal light), but not mild unilateral shade (60% normal light), reduced grain yield (37.6% to 54.4%, respectively). We further found that in unshaded leaves, Agpsl, Bmy, and Mexl-like expression significantly influenced sucrose and starch metabolism, while Sweet13a and Sut1 expression was crucial for sugar export. In shaded leaves, expression of Sps1, Agpsl, and Sweet13c was crucial for sugar metabolism and export. This study confirmed that unshaded leaves transported photosynthates to the ear, leading to a decrease in sugar concentration. The improvement of photosynthetic performance was associated with altered sugar transport. We propose a narrow-row spacing of 40 cm, which provides appropriate unilateral shade and limits yield reduction.

Alder expansion stimulates nitrogen oxide (NOx) emissions from southern Eurasian permafrost peatlands.

Nitrogen oxides (NOx) play an important role for atmospheric chemistry and radiative forcing. However, NOx emissions from the vast northern circumpolar permafrost regions have not been studied in situ due to limitations of measurement techniques. Our goals were to validate the offline analytical technique, and based on this, to widely quantify in situ NOx emissions from peatlands in the southern Eurasian permafrost region. To this end, we conducted a comparison of online and offline flux measurements in 2018 and 2019 using the synthetic air flushing, steady-state opaque chamber method. With differences in annual average and cumulative fluxes less than 0.1 µg N m-2 h-1 and 0.01 kg N ha-1 year-1, the online and offline fluxes were in good agreement, demonstrating the feasibility of conducting offline measurements in remote regions without power supply. The flux measurements over 2 years showed obvious NOx emissions of 0.05-0.14 and 0.13-0.30 kg N ha-1 year-1 in the hollow and hummock microtopography of permafrost peatlands, respectively. The rapid expansion of alder (Alnus sibirica) in the peatlands induced by permafrost degradation significantly increased soil mineral N contents and NOx emissions depending on the age of alder (0.64-1.74 and 1.44-2.20 kg N ha-1 year-1 from the alder forests with tree ages of 1-10 years and 11-20 years, respectively). Alder expansion also intensively altered the thermal state of permafrost including the sharp increases of soil temperatures during the non-growing season from October to April and active layer thickness. This study provides the first in situ evidences of NOx emissions from the northern circumpolar permafrost regions and uncovers the well-documented expansion of alders can substantially stimulate NOx emissions and thus, significantly affect air quality, radiative forcing, and ecosystem productivity in the pristine regions.

The advances of E2A-PBX1 fusion in B-cell acute lymphoblastic Leukaemia.

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches.

A nomogram model for predicting the efficacy of cyclosporine in patients with pure red cell aplasia.

Pure red cell aplasia (PRCA) is a rare bone marrow disorder characterized by a severe reduction or absence of erythroid precursor cells, without affecting granulocytes and megakaryocytes. Immunosuppressive therapies, particularly cyclosporine, have demonstrated efficacy as a primary treatment. This study aims to develop a predictive model for assessing the efficacy of cyclosporine in acquired PRCA (aPRCA). This retrospective study encompasses newly treated aPRCA patients at the General Hospital of Tianjin Medical University. Diagnosis criteria include severe anemia, and absolute reticulocyte count below 10 × 109/L, with normal white blood cell and platelet counts, and a severe reduction in bone marrow erythroblasts. Cyclosporine therapy was administered, with dose adjustments based on blood concentration. Response to cyclosporine was evaluated according to established criteria. Statistical analysis involved logistic multi-factor regression, generating a predictive model. The study included 112 aPRCA patients with a median age of 63.5 years. Patients presented with severe anemia (median Hb, 56 g/L) and reduced reticulocyte levels. Eighty-six patients had no bone marrow nucleated erythroblasts. Primary PRCA accounted for 62 cases (55.4%), and secondary PRCA accounted for 50 cases (44.6%). Univariate analysis revealed that ferritin, platelet to lymphocyte ratio (PLR), and CD4/CD8 ratio influenced treatment response. Multivariate analysis further supported the predictive value of these factors. A prediction model was constructed using ferritin, PLR, and CD4/CD8 ratio, demonstrating high sensitivity and specificity. The ferritin, PLR, and CD4/CD8-based nomogram showed good predictive ability for aPRCA response to cyclosporine. This model has potential clinical value for individualized diagnosis and treatment of aPRCA patients.

A case of visual impairment due to HHV-6 encephalitis after allogeneic hematopoietic stem cell transplantation in childhood acute myeloid leukemia-M2 subtype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a crucial treatment option for children with M2 subtype acute myeloid leukemia (AML). Human herpesvirus 6 (HHV-6) encephalitis following transplantation is a rare postoperative complication, with a poor prognosis and a high fatality rate in allo-HSCT recipients. In this report, a juvenile patient with AMLwas successfully treated after developing visual impairment as a result of HHV-6B encephalitis during allo-HSCT therapy. HHV-6 encephalitis-associated visual impairment after transplantation is rare, and clinical diagnosis and treatment are challenging, requiring more attention in the future.