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.

In vitro and in vivo activity of ceftazidime/avibactam and aztreonam alone or in combination against mcr-9, serine- and metallo-ß-lactamases-co-producing carbapenem-resistant Enterobacter cloacae complex.

PURPOSE: Enterobacteriaceae carrying mcr-9, in particularly those also co-containing metallo-ß-lactamase (MBL) and TEM type ß-lactamase, present potential transmission risks and lack adequate clinical response methods, thereby posing a major threat to global public health. The aim of this study was to assess the antimicrobial efficacy of a combined ceftazidime/avibactam (CZA) and aztreonam (ATM) regimen against carbapenem-resistant Enterobacter cloacae complex (CRECC) co-producing mcr-9, MBL and TEM. METHODS: The in vitro antibacterial activity of CZA plus ATM was evaluated using a time-kill curve assay. Furthermore, the in vivo interaction between CZA plus ATM was confirmed using a Galleria mellonella (G. mellonella) infection model. RESULTS: All eight clinical strains of CRECC, co-carrying mcr-9, MBL and TEM, exhibited high resistance to CZA and ATM. In vitro time-kill curve analysis demonstrated that the combination therapy of CZA + ATM exerted significant bactericidal activity against mcr-9, MBL and TEM-co-producing Enterobacter cloacae complex (ECC) isolates with a 100% synergy rate observed in our study. Furthermore, in vivo survival assay using Galleria mellonella larvae infected with CRECC strains co-harboring mcr-9, MBL and TEM revealed that the CZA + ATM combination significantly improved the survival rate compared to the drug-treatment alone and untreated control groups. CONCLUSION: To our knowledge, this study represents the first report on the in vitro and in vivo antibacterial activity of CZA plus ATM against CRECC isolates co-harboring mcr-9, MBL and TEM. Our findings suggest that the combination regimen of CZA + ATM provides a valuable reference for clinicians to address the increasingly complex antibiotic resistance situation observed in clinical microorganisms.

Coronary sodium [18F]fluoride activity predicts outcomes post-CABG: a comparative evaluation with conventional metrics.

PURPOSE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes. METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina. RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs. CONCLUSION: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity. TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

Relationship between self-psychological adjustment and post-traumatic growth in patients with lung cancer undergoing chemotherapy: a cross-sectional study.

OBJECTIVES: This study aimed to determine the potential profiles of self-psychological adjustment in patients with lung cancer undergoing chemotherapy, including sense of coherence (SOC) and positive cognitive emotion regulation (PCER). The relationship between these profiles with post-traumatic growth (PTG) and the relevant factors of self-psychological adjustment in different profiles was analysed. DESIGN: Cross-sectional study. SETTING: Patients with lung cancer undergoing chemotherapy in China. PARTICIPANTS: A total of 330 patients with lung cancer undergoing chemotherapy were recruited out of which 321 completed the questionnaires effectively. METHODS: Latent profile analysis was used to identify self-psychological adjustment classes based on the two subscales of the Sense of Coherence Scale and Cognitive Emotion Regulation Questionnaire. One-way analysis of variance and multinomial logistic regression were performed to examine the subgroup association with characteristics and PTG. RESULTS: Three latent profiles of self-psychological adjustment were identified: low level (54.5%), high SOC-low PCER (15.6%) and high PCER (29.9%). The results of univariate analysis showed a significant difference in PTG scores among different self-psychological adjustment subgroups (F=11.55, p<0.001). Patients in the high-PCER group were more likely living in urban areas (OR=2.41, 95% CI 1.17 to 4.97, p=0.02), and time since cancer diagnosis was ≥6 months and <1 year (OR=3.54, 95% CI 1.3 to 9.64, p<0.001). CONCLUSION: This study revealed that most patients with lung cancer undergoing chemotherapy belonged to the low-level group. Three profiles are associated with PTG. There were differences in characteristics between patients treated with chemotherapy for lung cancer in the high-PCER and low-PCER groups. Thus, these profiles provide useful information for developing targeted individualised interventions based on demographic characteristics that would assist PTG in patients with lung cancer undergoing chemotherapy.

Analysis of the effect on costochondral graft for TMJ ankylosis with jaw deformities in pediatrics.

OBJECTIVES: To evaluate the effects of costochondral grafting (CCG) used for temporomandibular joint ankylosis (TMJA) in growing patients. MATERIALS AND METHODS: Pediatric patients with TMJA treated by CCG from 2010.5 to 2021.7 were included in the study. CT scans were performed before and after operations with at least 1 year follow-up. The height of the mandibular ramus, menton deviation or retraction, osteotomy gap, etc. were measured by ProPlan CMF1.4 software. CCG growth, resorption, and relapse were evaluated and analyzed with influencing factors such as age, ostectomy gap, etc. by generalized estimating equation. RESULTS: There were 24 patients (29 joints) with an average age of 6.30 ± 3.13 years in the study. After operation, the mandibular ramus was elongated by 5.97 ± 3.53 mm. Mandibular deviation or retrusion was corrected by 4.82 ± 2.84 mm and 3.76 ± 2.97 mm respectively. After a mean follow-up of 38.91 ± 29.20 months, 58.62% CCG grew (4.18 ± 7.70 mm), 20.69% absorbed (2.23 ± 1.16 mm), and 20.69% re-ankylosed. The re-ankylosis was negatively correlated with the osteotomy gap (OR:0.348,0.172-0.702 95%CI, critical value = 6.10 mm). CCG resorption was positively correlated with the distance of CCG ramus elongation (OR:3.353,1.173-9.586 95%CI, critical value = 7.40 mm). CONCLUSIONS: An adequate osteotomy gap and CCG ramus elongation distance are the key factors for successful treatment of TMJA with jaw deformities in growing patients. CLINICAL RELEVANCE: TMJA affects mouth opening and jaw development in pediatric patients. The most common autogenous bone graft for pediatric patients is CCG due to its growth potential, convenient access and easy contouring. Also, it can simultaneously reconstruct the TMJ and improve jaw deformity by lengthening the mandibular ramus. But the growth of CCG is unpredictable. In this study, we explored several factors that may affect the absorption and re-ankylosis of CCG, expecting to provide several suggestions to improve future CCG treatment.

Transcriptomic analysis of induced resistance to polymyxin in carbapenem-resistant Enterobacter cloacae complex isolate carrying mcr-9.

OBJECTIVES: Polymyxins are currently the last-resort treatment against multi-drug resistant Gram-negative bacterial infections, but plasmid-mediated mobile polymyxin resistance genes (mcr) threaten its efficacy, especially in carbapenem-resistant Enterobacter cloacae complex (CRECC). The objective of this study was to provide insights into the mechanism of polymyxin-induced bacterial resistance and the effect of overexpression of mcr-9. METHODS: The clinical strain CRECC414 carrying the mcr-9 gene was treated with a gradient concentration of polymyxin. Subsequently, the broth microdilution was used to determine the minimum inhibitory concentration (MIC) and RT-qPCR was utilized to assess mcr-9 expression. Transcriptome sequencing and Whole genome sequencing (WGS) was utilized to identify alterations in strains resulting from increased polymyxin resistance, and significant transcriptomic differences were analyzed alongside a comprehensive examination of metabolic networks at the genomic level. RESULTS: Polymyxin treatment induced the upregulation of mcr-9 expression and significantly elevated the MIC of the strain. Furthermore, the WGS and transcriptomic results revealed a remarkable up-regulation of arnBCADTEF gene cassette, indicating that the Arn/PhoPQ system-mediated L-Ara4N modification is the preferred mechanism for achieving high levels of resistance. Additionally, significant alterations in bacterial gene expression were observed with regards to multidrug efflux pumps, oxidative stress and repair mechanisms, cell membrane biosynthesis, as well as carbohydrate metabolic pathways. CONCLUSION: Polymyxin greatly disrupts the transcription of vital cellular pathways. A complete PhoPQ two-component system is a prerequisite for polymyxin resistance of Enterobacter cloacae, even though mcr-9 is highly expressed. These findings provide novel and important information for further investigation of polymyxin resistance of CRECC.

Recent Advances in Self-Assembled Molecular Application in Solar Cells.

Perovskite solar cells (PSCs) have attracted much attention due to their low cost, high efficiency, and solution processability. With the development of various materials in perovskite solar cells, self-assembled monolayers (SAMs) have rapidly become an important factor in improving power conversion efficiency (PCE) due to their unique physical and chemical properties and better energy level matching. In this topical review, we introduced important categories of self-assembled molecules, energy level modulation strategies, and various characteristics of self-assembled molecules. In addition, we focused on reviewing the application of self-assembled molecules in solar cells, and explained the changes that self-assembled molecules bring to PSCs by introducing the mechanism and effect of self-assembled molecules. Finally, we also elaborated on the challenges currently faced by self-assembled molecules and provided prospects for their applications in other optoelectronic devices.

K-clip™, a Novel Transcatheter Treatment in Patients with Severely Tricuspid Regurgitation.

Patients who suffer from severe tricuspid regurgitation (TR) and who are at high surgical risk have no standard care therapy. Therefore, minimally invasive and safer methods are sought. K-clip™, the first ultrasound-positioned interventional tricuspid annuloplasty instrument intended for percutaneous transcatheter repair. We report a patient with severe functional TR and high surgical risk who underwent K-clip™ tricuspid annuloplasty under echocardiography and fluoroscopy guidance.

N2O emission in temperate seagrass meadows: Fluxes, pathway and molecular mechanism.

Seagrass meadows act as filters for nitrogen in coastal areas, but whether they are a source or sink for N2O has been still controversy. Additionally, the production pathways of N2O as well as the microbial driving mechanism in seagrass meadows are seldom reported. In this study, the air-sea fluxes, sediment release potential, and production pathway of N2O in a temperate Zostera marina and Z. japonica mixed meadow were investigated by using gas chromatography and 15N isotopic tracing methods. The qPCR and metagenome sequencing were used to compare the difference in functional gene abundance and expression between seagrass vegetated and non-grass sediments. The results showed that the N2O air-sea fluxes in the meadow ranged from -1.97 to -1.77 nmol m⁻2 h⁻1, which was slightly lower in the seagrass region than in the adjacent bare region. Seagrass sediment N2O release potential dramatically increased after warming and nitrogen enrichment treatments. Heterotrophic nitrification was firstly investigated in seagrass meadows, and the process (26.80%-62.41%) and denitrification (37.55%-72.83%) contributed significantly to N2O production in the meadow, affected deeply by sediment organic content, while the contribution of autotrophic nitrification can be neglected. Compared with the bare sediments, the ammonia monooxygenase genes amoA, amoB and amoC, and nitrite oxidoreductase genes nxrA and nxrB, as well as nitrite reductase gene nirS and nitric oxide reductase gene norB were down-regulated, while the nitrous oxide reductase gene nosZ was up-regulated in the seagrass sediments, explaining less N2O emission in seagrass regions from the perspective of molecular. The nosZII-bearing bacteria like Bacteroidia, Polyangia, Anaerolineae, and Verrucomicrobiae could play important roles in N2O reduction in the seagrass meadow. The result is of great significance for highlighting the ability of seagrass meadows to mitigate climate changes.

A Comprehensive Review on Circulating cfRNA in Plasma: Implications for Disease Diagnosis and Beyond.

Circulating cfRNA in plasma has emerged as a fascinating area of research with potential applications in disease diagnosis, monitoring, and personalized medicine. Circulating RNA sequencing technology allows for the non-invasive collection of important information about the expression of target genes, eliminating the need for biopsies. This comprehensive review aims to provide a detailed overview of the current knowledge and advancements in the study of plasma cfRNA, focusing on its diverse landscape and biological functions, detection methods, its diagnostic and prognostic potential in various diseases, challenges, and future perspectives.

Exogenous indole-3-acetic acid promotes the plant growth and accumulation of selenium in grapevine under selenium stress.

To alleviate the selenium (Se) stress in fruit trees and improve its accumulation, the effects of exogenous indole-3-acetic acid (IAA) on the growth and Se accumulation of grapevine under Se stress were studied. The application of exogenous IAA increased the biomass of grapevine, and the concentration of exogenous IAA had a regression relationship with the biomass. The root and shoot biomass were the maximum at 60 mg L- 1 IAA, increasing by 15.61% and 23.95%, respectively, compared with the control. Exogenous IAA also increased the photosynthetic pigments and the activities of superoxide dismutase and peroxidase in grapevine. Moreover, exogenous IAA increased the contents of total Se, organic Se, and inorganic Se, and the concentration of exogenous IAA had a regression relationship with the total Se content. The highest contents of root total Se and shoot total Se were accumulated at 90 mg L- 1 IAA, increasing by 29.94% and 55.77% respectively,. In addition, the correlation and path analyses revealed that the carotenoid content and root total Se content were closely associated with the shoot total Se content. Therefore, the application of exogenous IAA can alleviate the stress of Se to grape and promote its uptake and the most effective amount for the uptake of Se is 90 mg L- 1 IAA.

miR-133a and miR-135a Regulate All-Trans Retinoic Acid-Mediated Differentiation in Pediatric Acute Myeloid Leukemia by Inhibiting CDX2 Translation and Serve as Prognostic Biomarkers.

Background: Acute myeloid leukemia (AML) is a type of blood cancer characterized by excessive growth of immature myeloid cells. Unfortunately, the prognosis of pediatric AML remains unfavorable. It is imperative to further our understanding of the mechanisms underlying leukemogenesis and explore innovative therapeutic approaches to enhance overall disease outcomes for patients with this condition. Methods: Quantitative reverse-transcription PCR was used to quantify the expression levels of microRNA (miR)-133a and miR-135a in 68 samples from 59 pediatric patients with AML. Dual-luciferase reporter transfection assay, Cell Counting Kit-8 assay, and western blot analysis were used to investigate the functions of miR-133a and miR-135a. Results: Our study found that all-trans-retinoic acid (ATRA) promoted the expression of miR-133a and miR-135a in AML cells, inhibited caudal type homeobox 2 (CDX2) expression, and subsequently inhibited the proliferation of AML cells. Additionally, miR-133a and miR-135a were highly expressed in patients with complete remission and those with better survival. Conclusions: miR-133a and miR-135a may play an antioncogenic role in pediatric AML through the ATRA-miRNA133a/135a-CDX2 pathway. They hold promise as potentially favorable prognostic indicators and novel therapeutic targets for pediatric AML.

Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer.

BACKGROUND: The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors. METHODS: The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT. RESULTS: After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2 = 0.319, P = 0.037, and BMD was also positively correlated with pectoral muscle density, R2 = 0.329, P = 0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism. CONCLUSION: Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.

Microglia-targeted inhibition of miR-17 via mannose-coated lipid nanoparticles improves pathology and behavior in a mouse model of Alzheimer's disease.

Neuroinflammation and accumulation of Amyloid Beta (Aß) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aß accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aß burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.

Genomic analyses reveal the stepwise domestication and genetic mechanism of curd biogenesis in cauliflower.

Cauliflower (Brassica oleracea L. var. botrytis) is a distinctive vegetable that supplies a nutrient-rich edible inflorescence meristem for the human diet. However, the genomic bases of its selective breeding have not been studied extensively. Herein, we present a high-quality reference genome assembly C-8 (V2) and a comprehensive genomic variation map consisting of 971 diverse accessions of cauliflower and its relatives. Genomic selection analysis and deep-mined divergences were used to explore a stepwise domestication process for cauliflower that initially evolved from broccoli (Curd-emergence and Curd-improvement), revealing that three MADS-box genes, CAULIFLOWER1 (CAL1), CAL2 and FRUITFULL (FUL2), could have essential roles during curd formation. Genome-wide association studies identified nine loci significantly associated with morphological and biological characters and demonstrated that a zinc-finger protein (BOB06G135460) positively regulates stem height in cauliflower. This study offers valuable genomic resources for better understanding the genetic bases of curd biogenesis and florescent development in crops.

[Clinical and genetic analysis of three children with Hyperekplexia].

OBJECTIVE: To explore the clinical and genetic characteristics of three children with Hyperekplexia. METHODS: Three children who were diagnosed with Hyperekplexia at the Third Affiliated Hospital of Zhengzhou University between June 2018 and March 2020 were selected as the study subjects. Clinical data of the three children were collected. All children were subjected to whole exome sequencing. Pathogenicity of candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The three children were all males, and had presented exaggerated startle reflexes and generalized stiffness in response to unexpected auditory or tactile stimulation, or had frequent traumatic falls following exaggerated startle. All children had shown positive nose-tapping reflex, though EEG and cranial MRI exams were all negative. Whole exome sequencing revealed that two children had harbored homozygous variants of the GLRB gene, of which the c.1017_c.1018insAG (p.G340Rfs*14) was unreported previously. The third child had harbored compound heterozygous variants of the GLRA1 gene, among which the c.1262T>A (p.IIe421Asn) variant showed an unreported autosomal recessive inheritance. All children had responded well to clonazepam treatment. CONCLUSION: Patients with Hyperekplexia have typical clinical manifestations. Early clinical identification and genetic analysis can facilitate their diagnosis.

Adaptation mechanism of three Impatiens species to different habitats based on stem morphology, lignin and MYB4 gene.

BACKGROUND: Impatiens is an important genus with rich species of garden plants, and its distribution is extremely extensive, which is reflected in its diverse ecological environment. However, the specific mechanisms of Impatiens' adaptation to various environments and the mechanism related to lignin remain unclear. RESULTS: Three representative Impatiens species,Impatiens chlorosepala (wet, low degree of lignification), Impatiens uliginosa (aquatic, moderate degree of lignification) and Impatiens rubrostriata (terrestrial, high degree of lignification), were selected and analyzed for their anatomical structures, lignin content and composition, and lignin-related gene expression. There are significant differences in anatomical parameters among the stems of three Impatiens species, and the anatomical structure is consistent with the determination results of lignin content. Furthermore, the thickness of the xylem and cell walls, as well as the ratio of cell wall thickness to stem diameter have a strong correlation with lignin content. The anatomical structure and degree of lignification in Impatiens can be attributed to the plant's growth environment, morphology, and growth rate. Our analysis of lignin-related genes revealed a negative correlation between the MYB4 gene and lignin content. The MYB4 gene may control the lignin synthesis in Impatiens by controlling the structural genes involved in the lignin synthesis pathway, such as HCT, C3H, and COMT. Nonetheless, the regulation pathway differs between species of Impatiens. CONCLUSIONS: This study demonstrated consistency between the stem anatomy of Impatiens and the results obtained from lignin content and composition analyses. It is speculated that MYB4 negatively regulates the lignin synthesis in the stems of three Impatiens species by regulating the expression of structural genes, and its regulation mechanism appears to vary across different Impatiens species. This study analyses the variations among different Impatiens plants in diverse habitats, and can guide further molecular investigations of lignin biosynthesis in Impatiens.

Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy.

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.

Research Progress of Heavy-Metal-Free Quantum Dot Light-Emitting Diodes.

At present, heavy-metal-free quantum dot light-emitting diodes (QLEDs) have shown great potential as a research hotspot in the field of optoelectronic devices. This article reviews the research on heavy-metal-free quantum dot (QD) materials and light-emitting diode (LED) devices. In the first section, we discussed the hazards of heavy-metal-containing quantum dots (QDs), such as environmental pollution and human health risks. Next, the main representatives of heavy-metal-free QDs were introduced, such as InP, ZnE (E=S, Se and Te), CuInS2, Ag2S, and so on. In the next section, we discussed the synthesis methods of heavy-metal-free QDs, including the hot injection (HI) method, the heat up (HU) method, the cation exchange (CE) method, the successful ionic layer adsorption and reaction (SILAR) method, and so on. Finally, important progress in the development of heavy-metal-free QLEDs was summarized in three aspects (QD emitter layer, hole transport layer, and electron transport layer).

The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity.

Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i's) in combination with chemotherapy have shown promising results in preclinical studies but have displayed minimal efficacy with substantial toxicity in clinical trials. To explore combinatorial strategies that can overcome these limitations, we perform an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identify thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a determinant of CHK1i sensitivity. We establish a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR inhibitor auranofin, an approved anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, we show a pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.