Development of a base editor for convenient and multiplex genome editing in cyanobacteria.

Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C → T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.

Postmenopausal giant uterine adenomyoma with adipose metaplasia: A case report and literature review.

RATIONALE: Uterine adenomyomas (UAs) are common benign tumors, usually not exceeding 280 g or the weight of the uterus at 12 weeks gestation. Postmenopausal giant UAs of diameter larger than 20 cm are rare, as well as steatosis, but curable by surgical excision. Few cases of postmenopausal giant UAs have been reported. PATIENT CONCERNS: Herein, we report a case of a 70-year-old female patient who presented with a giant pelvic tumor of about 20 cm × 18 cm × 20 cm with postmenopausal vaginal bleeding, and whose radiographic manifestations did not exclude the possibility of uterine malignancy. DIAGNOSES: Histopathology confirms an adenomyoma with partial adipose metaplasia. INTERVENTIONS: We did an open laparotomy of hysterectomy, bi-adnexectomy, and pelvic adhesion release for the patient. OUTCOMES: Pathology revealed adenomyoma with adipose metaplasia. The patient recovered well and was discharged on postoperative day 7 with satisfactory follow-up.

Prenatal diagnosis and genetic study of 22q11.2 microduplication in Chinese fetuses: A series of 31 cases and literature review.

BACKGROUND: Patients with 22q11.2 microduplication syndrome exhibit a high degree of phenotypic heterogeneity and incomplete penetrance, making prenatal diagnosis challenging due to phenotypic variability. This report aims to raise awareness among prenatal diagnostic practitioners regarding the variant's complexity, providing a basis for prenatal genetic counseling. METHODS: Family and clinical data of 31 fetuses with 22q11.2 microduplications confirmed by chromosomal microarray between June 2017 and June 2023 were considered. RESULTS: Primary prenatal ultrasound features of affected fetuses include variable cardiac and cardiovascular anomalies, increased nuchal translucency (≥3 mm), renal abnormalities, and polyhydramnios. More than half of fetuses considered showed no intrauterine manifestations; therefore, prenatal diagnostic indicators were primarily advanced maternal age or high-risk Down syndrome screening. Most fetuses had microduplications in proximal or central 22q11.2 regions, with only three cases with distal microduplications. Among parents of fetuses considered, 87% (27/31) continued the pregnancy. During follow-up, 19 cases remained clinically asymptomatic. CONCLUSION: Nonspecific 22q11.2 microduplication features in fetuses and its mild postnatal disease presentation highlight the need to cautiously approach prenatal diagnosis and pregnancy decision-making. Increased clinical efforts should be made regarding providing parents with specialized genetic counseling, long-term follow-up, and fetal risk information.

Prenatal diagnosis and genetic analysis of small supernumerary marker chromosomes in the eastern chinese han population: A retrospective study of 36 cases.

BACKGROUND: Small supernumerary marker chromosomes (sSMCs) are additional chromosomes with unclear structures and origins, and their correlations with clinical fetal phenotypes remain incompletely understood, which reduces the accuracy of genetic counseling. METHODS: We conducted a retrospective analysis of a cohort of 36 cases of sSMCs diagnosed in our center. We performed G-banding and chromosomal microarray analysis (CMA). The resulting karyotypes were compared with case reports in the literature and various databases including OMIM, DECIPHER, ClinVar, ClinGen, ISCA, DGV, and PubMed. RESULTS: Karyotype analysis data revealed that 19 out of 36 fetuses were mosaic. Copy number variants (CNVs) analysis results showed that 27 out of 36 fetuses harbored pathogenic/likely pathogenic variants. Among these 27 cases, 11 fetuses carried sex chromosome-related CNVs, including 4 female cases exhibiting Turner syndrome phenotypes and 7 cases showing Y chromosome deletions. In the remaining 16 fetuses with autosomal CNVs, 9 fetuses carried variants associated with Cat eye syndrome, Emanuel syndrome, Tetrasomy 18p, and 15q11-q13 duplication syndrome. Among these, 22 fetuses were terminated, and the remaining 5 fetuses were delivered and developed normally. Additionally, we identified a few variants with unclear pathogenicity. CONCLUSION: Cytogenetic analysis is essential for identifying the pathogenicity of sSMCs and increasing the accuracy of genetic counseling.

Fetal agenesis of corpus callosum: chromosomal copy number abnormalities and postnatal follow-up.

OBJECTIVE: Agenesis of the corpus callosum (ACC) is an anomaly that can occur in fetuses during pregnancy. However, there is currently no treatment for fetal ACC. Therefore, we conducted a retrospective analysis of obstetric outcomes of fetal ACC to explore the relationship between fetal ACC phenotypes and chromosomal copy number abnormalities. METHODS AND RESULTS: Amniotic fluid or umbilical cord blood were extracted from pregnant women with fetal ACC for karyotype analysis and chromosomal microarray analysis (CMA). Among the 48 fetuses with ACC, 22 (45.8%, 22/48) had isolated ACC, and 26 (54.2%, 26/48) had non-isolated ACC. Chromosomal abnormalities were detected via karyotype analysis in four cases. In addition to the four cases of pathogenic copy number variations (CNVs) detected using karyotype analysis, CMA revealed two cases of pathogenic CNVs with 17q12 microduplication and 16p12.2 microdeletion. The obstetric outcomes of 26 patients with non-isolated ACC were followed up, and 17 chose to terminate the pregnancy. In addition, seven of the nine cases with non-isolated ACC showed no obvious abnormality during postnatal follow-up, whereas only one case with normal CMA showed an abnormal phenotype at six months. Of the 22 patients with isolated ACC, six chose to terminate the pregnancy. Postnatal follow-up of 16 isolated ACC cases revealed only one with benign CNV, presenting with intellectual disability. CONCLUSION: Pregnant women with fetal ACC should be offered prenatal CMA, particularly non-isolated ACC. Patients with ACC should undergo prolonged postnatal follow-up, and appropriate intervention should be provided if necessary.

Prenatal genetic diagnosis of fetuses with dextrocardia using whole exome sequencing in a tertiary center.

To evaluate the genetic etiology of fetal dextrocardia, associated ultrasound anomalies, and perinatal outcomes, we investigated the utility of whole exome sequencing (WES) for prenatal diagnosis of dextrocardia. Fetuses with dextrocardia were prospectively collected between January 2016 and December 2022. Trio-WES was performed on fetuses with dextrocardia, following normal karyotyping and/or chromosomal microarray analysis (CMA) results. A total of 29 fetuses with dextrocardia were collected, including 27 (93.1%) diagnosed with situs inversus totalis and 2 (6.9%) with situs inversus partialis. Cardiac malformations were present in nine cases, extra-cardiac anomalies were found in seven cases, and both cardiac and extra-cardiac malformations were identified in one case. The fetal karyotypes and CMA results of 29 cases were normal. Of the 29 cases with dextrocardia, 15 underwent WES, and the other 14 cases refused. Of the 15 cases that underwent WES, clinically relevant variants were identified in 5/15 (33.3%) cases, including the diagnostic variants DNAH5, DNAH11, LRRC56, PEX10, and ZIC3, which were verified by Sanger sequencing. Of the 10 cases with non-diagnostic results via WES, eight (80%) chose to continue the pregnancies. Of the 29 fetuses with dextrocardia, 10 were terminated during pregnancy, and 19 were live born. Fetal dextrocardia is often accompanied by cardiac and extra-cardiac anomalies, and fetal dextrocardia accompanied by situs inversus is associated with a high risk of primary ciliary dyskinesia. Trio-WES is recommended following normal karyotyping and CMA results because it can improve the diagnostic utility of genetic variants of fetal dextrocardia, accurately predict fetal prognosis, and guide perinatal management and the reproductive decisions of affected families.

Thermoelectric-Feedback Nanocomposite Hydrogel for Temperature-Synchronized Monitoring and Regulation in Accurate Photothermal Therapy.

Photothermal therapy (PTT) is a promising approach for tumor ablation and cancer treatment. However, controlling the therapeutic temperature during treatment remains challenging, and imprecise thermal regulation can harm adjacent healthy tissues, reduce therapeutic accuracy, and promote the thermotolerance of cellular phenotypes, potentially leading to tumor invasion and recurrence. Although existing methods provide basic temperature control by adjusting irradiation power and photothermal agent dosing, they lack real-time temperature monitoring and feedback control capabilities, underscoring the urgent need for more integrated and precise PTT systems. In this context, an innovative photothermoelectric (PTE) cobalt-infused chitosan (CS) nanocomposite hydrogel (PTE-Co@CS) is developed for precise temperature-regulated PTT, exhibiting desirable mechanical properties and exceptional biocompatibility. Enhanced by embedded nanoparticles, PTE-Co@CS demonstrates superior photothermal conversion efficiency compared with existing methods, while also featuring thermoelectric responsiveness and increased sensitivity to photostimuli. Its advantageous PTE response characteristics ensure a linear correlation between temperature shifts and resistance changes (e.g., R2 = 0.99919 at 0.5 W cm⁻2), enabling synchronized qualitative and quantitative control of PTT temperature through electrical signal monitoring. This allows for real-time monitoring and regulation during PTT, effectively addressing the issue of uncontrollable temperatures and improving therapeutic efficacy.

A highly specific and ultrasensitive approach to detect Prymnesium parvum based on RPA-CRISPR-LbaCas12a-LFD system.

BACKGROUND: Harmful algal blooms (HABs), caused by the rapid proliferation or aggregation of microorganisms, are catastrophic for the environment. The Prymnesium parvum is a haptophyte algal species that is found worldwide and is responsible for extensive blooms and death of larval amphibians and bivalves, causing serious negative impacts on the ecological environment. For the prevention and management of environmental pollution, it is crucial to explore and develop early detection strategies for HABs on-site using simple methods. The major challenge related to early detection is the accurate and sensitive detection of algae present in low abundance. RESULTS: Herein, recombinase polymerase amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats and Cas12a protein (CRISPR-LbaCas12a) systems, and the lateral flow dipstick (LFD) was used for the first time for early detection of P. parvum. The internal transcribed spacer (ITS) of P. parvum was selected as the target sequence, and the concentration of single-strand DNA reporters, buffer liquid system, reaction time, and amount of gold particles were optimized. The RPA-CRISPR-LbaCas12a-LFD approach demonstrated highly specificity during experimental testing, with no cross-reaction against different microalgae used as controls. In addition, the lowest detection limit was 10,000 times better than the lowest detection limit of the standalone RPA approach. The feasibility and robustness of this approach were further verified by using the different environmental samples. It also observed that P. parvum are widely distributed in Chinese Sea, but the cell density of P. parvum is relatively low (<0.1 cells/mL). SIGNIFICANCE: The developed approach has an excellent specificity and offers 10,000 times better sensitivity than the standalone RPA approach. These advantages make this approach suitable for early warning detection and prevention of HAB events in environmental water. Also, the outcomes of this study could promote a shift from traditional laboratory-based detection to on-site monitoring, facilitating early warning against HABs.

Interactions between the nitrogen-fixing cyanobacterium Trichodesmium and siderophore-producing cyanobacterium Synechococcus under iron limitation.

As diazotrophic cyanobacteria of tremendous biomass, Trichodesmium continuously provide a nitrogen source for carbon-fixing cyanobacteria and drive the generation of primary productivity in marine environments. However, ocean iron deficiencies limit growth and metabolism of Trichodesmium. Recent studies have shown the co-occurrence of Trichodesmium and siderophore-producing Synechococcus in iron-deficient oceans, but whether siderophores secreted by Synechococcus can be used by Trichodesmium to adapt to iron deficiency is not clear. We constructed a mutant Synechococcus strain unable to produce siderophores to explore this issue. Synechococcus filtrates with or without siderophores were added into a Trichodesmium microbial consortium consisting of Trichodesmium erythraeum IMS 101 as the dominant microbe with chronic iron deficiency. By analyzing the physiological phenotype, metagenome, and metatranscriptome, we investigated the interactions between the nitrogen-fixing cyanobacterium Tricodesmium and siderophore-producing cyanobacterium Synechococcus under conditions of iron deficiency. The results indicated that siderophores secreted by Synechococcus are likely to chelate with free iron in the culture medium of the Trichodesmium consortium, reducing the concentration of bioavailable iron and posing greater challenges to the absorption of iron by Trichodesmium. These findings revealed the characteristics of iron-competitive utilization between diazotrophic cyanobacteria and siderophore-producing cyanobacteria, as well as potential interactions, and provide a scientific basis for understanding the regulatory effects of nutrient limitation on marine primary productivity.

Identification and bioinformatics analysis of genes associated with pyroptosis in spinal cord injury of rat and mouse.

The mechanism of spinal cord injury (SCI) is highly complex, and an increasing number of studies have indicated the involvement of pyroptosis in the physiological and pathological processes of secondary SCI. However, there is limited bioinformatics research on pyroptosis-related genes (PRGs) in SCI. This study aims to identify and validate differentially expressed PRGs in the GEO database, perform bioinformatics analysis, and construct regulatory networks to explore potential regulatory mechanisms and therapeutic targets for SCI. We obtained high-throughput sequencing datasets of SCI in rats and mice from the GEO database. Differential analysis was conducted using the "limma" package in R to identify differentially expressed genes (DEGs). These genes were then intersected with previously reported PRGs, resulting in a set of PRGs in SCI. GO and KEGG enrichment analyses, as well as correlation analysis, were performed on the PRGs in both rat and mouse models of SCI. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING website to examine the relationships between proteins. Hub genes were identified using Cytoscape software, and the intersection of the top 5 hub genes in rats and mice were selected for subsequent experimentally validated. Furthermore, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory mechanisms. The gene expression profiles of GSE93249, GSE133093, GSE138637, GSE174549, GSE45376, GSE171441_3d and GSE171441_35d were selected in this study. We identified 10 and 12 PRGs in rats and mice datasets respectively. Six common DEGs were identified in the intersection of rats and mice PRGs. Enrichment analysis of these DEGs indicated that GO analysis was mainly focused on inflammation-related factors, while KEGG analysis showed that the most genes were enriched on the NOD-like receptor signaling pathway. We constructed a ceRNA regulatory network that consisted of five important PRGs, as well as 24 miRNAs and 34 lncRNAs. This network revealed potential regulatory mechanisms. Additionally, the three hub genes obtained from the intersection were validated in the rat model, showing high expression of PRGs in SCI. Pyroptosis is involved in secondary SCI and may play a significant role in its pathogenesis. The regulatory mechanisms associated with pyroptosis deserve further in-depth research.

HT-NMR Studies of the Be-F Coordination Structure in FNaBe and FLiBe Mixed Salts.

Molten NaF-BeF2 salt is widely considered a promising candidate to replace FLiBe in molten salt reactor applications, which is crucial to reducing the operating costs of the molten salt reactor. Studies on beryllium compounds are rarely conducted due to their volatility and high toxicity. Herein, the Be-F coordination structure of NaF/BeF2 mixed salts was investigated in-depth through various HT-NMR and solid-state NMR methods, which are optimized to be appropriate for the detection of beryllium compounds. It was found that Na2BeF4 and NaBeF3 crystals were transformed into amorphous tetrahedral coordinated networks when there was an increase in the BeF2 concentration in the mixed salts. The main coordinate structure comparisons between FNaBe and FLiBe were analyzed, which exhibit high similarity due to the covalent effect of Be-F bonding, demonstrating the theoretical feasibility of applying FNaBe salts as a substitute for FLiBe in MSR systems. In addition, the transition from the crystal phase to the amorphous phase occurred at a lower BeF2 concentration for FNaBe than that for FLiBe. This was further verified by the results of ab initio molecular dynamics (AIMD) simulation that FNaBe melts had more disordered structures, thus causing slight changes in their physical properties.

Analysis of multiple factors influencing the survival of patients with advanced gastric cancer.

OBJECTIVE: The aim of this study was to investigate the main factors influencing the survival of patients with advanced gastric cancer. METHODS: The clinicopathological data of 120 patients with advanced gastric cancer were analyzed retrospectively, and clinical and pathological data were collected. Tumor tissue staging and grading were re-evaluated, and 5-year overall survival was followed up. The classified data were described by percentages, and the continuous data were described by standard deviations or medians. Univariate analysis was performed using the χ2 test or rank-sum test, followed by Kaplan-Meier survival analysis to calculate the median survival time and 5-year cumulative survival. A multivariate Cox regression model was used to evaluate the independent risk factors affecting survival. The test level was α = 0.05. RESULTS: Patients were followed up for 0 to 60 months, the 5-year overall survival rate was 36.2%, and the median survival time was 53.0 ± 1.461 months. K-M and log-rank test results revealed that tumor location, degree of differentiation, depth of invasion, regional lymph node involvement, and postoperative tumor stage were correlated with a decreased 5-year survival rate (P < 0.05). A multivariate Cox risk regression model was used to analyze the degree of histological differentiation (HR = 1.441; 95% CI = 1.049-1.979; P = 0.024), regional lymph node (HR = 1.626; 95% CI = 1.160-2.279; P = 0.005), and pTNM stage (HR = 2.266; 95% CI = 1.335-3.847; P = 0.002), which are independent risk factors for poor survival. Tumor location (P = 0.191), invasion depth (P = 0.579) and tumor size (P = 0.324) were not found to be independent risk factors. CONCLUSION: The degree of tumor differentiation, regional lymph node metastasis and postoperative pathological stage were found to be independent risk factors for 5-year overall survival in patients with advanced gastric cancer. Standardized and reasonable lymph node dissection and accurate postoperative pathological staging were very important.

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations.

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

[Advance of research on the role of BCL11A in the occurrence and treatment of ß-Thalassemia].

ß-Thalassemia is a single-gene disease caused by mutations in ß-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/ß hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for ß-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of ß-thalassemia.

Diversity and distribution analysis of eukaryotic communities in the Xiangshan Bay, East China sea by metabarcoding approach.

Eukaryotic communities play an important role in the coastal ecosystem of Xiangshan Bay, a narrow semi-closed bay famous for fisheries and marine farming. However, information on the diversity and composition of eukaryotic communities in Xiangshan Bay remains unclear. In this study, the metabarcoding approach was utilized to comprehensively investigate the eukaryotic plankton community structure and dominant taxa, particularly eukaryotic microalgae, in the Xiangshan Bay over a period of four months in 2018. The results showed that the three major phyla were Arthropoda, Chlorophyta, and Bacillariophyta. The richness indices revealed that species richness peaked in February and was at its lowest in May. Diversity indices showed that the samples collected in May had the lowest diversity. Centropages was detected in the samples of all months, however, its highest dominance was observed in the samples collected in February. In addition, compared to other months, a greater proportion of eukaryotic microalgae was witnessed in March. The three eukaryotic algae with highest abundances in March were Cyclotella, Prorocentrum, and Thalassiosira. Moreover, high diversity of pico-sized (0.2-2.0 µm) phytoplankton (which are often easily missed by microscopy) was discovered in this study by using metabarcoding approach. This study highlights the strength and significance of the metabarcoding approach to uncover a large number of eukaryotic species which remains undetectable during application of conventional approaches. The findings of this study reveals that the eukaryotic community structure varies noticeably in both time and space throughout sampling period, with temperature being the most important environmental factor influencing these changes. This study lays a solid foundation to understand eukaryotic plankton composition, temporal and spatial dynamics and the distribution mechanism of eukaryotic plankton community in Xiangshan Bay, providing theoretical reference for further studies related to marine ecology.

Regulation of N6-methyladenosine modification in erythropoiesis and thalassemia.

In eukaryotic RNA, N6-methyladenosine (m6A) is a prevalent form of methylation modification. The m6A modification process is reversible and dynamic, written by m6A methyltransferase complex, erased by m6A demethylase, and recognized by m6A binding proteins. Through mediating RNA stability, decay, alternative splicing, and translation processes, m6A modification regulates gene expression at the post-transcriptional level. Erythropoiesis is the process of hematopoietic stem cells undergoing proliferation, a series of differentiation and maturation to form red blood cells (RBCs). Thalassemia is a common monogenic disease characterized by excessive production of ineffective RBCs in the peripheral circulation, resulting in hemolytic anemia. Increasing evidence suggests that m6A modification plays a crucial role in erythropoiesis. In this review, we comprehensively summarize the function of m6A modification in erythropoiesis and further generalize the mechanism of m6A modification regulating ineffective erythropoiesis and fetal hemoglobin expression. The purpose is to improve the understanding of the pathogenesis of erythroid dysplasia and offer new perspectives for the diagnosis and treatment of thalassemia.

Post-translational modifications in diabetic cardiomyopathy.

The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling the pathogenesis of diabetic cardiomyopathy, with a particular emphasis on investigating various post-translational modifications. These modifications dynamically regulate protein function in response to changes in the internal and external environment, and their disturbance of homeostasis holds significant relevance for the development of chronic ailments. This review provides a comprehensive overview of the common post-translational modifications involved in the initiation and progression of diabetic cardiomyopathy, including O-GlcNAcylation, phosphorylation, methylation, acetylation and ubiquitination. Additionally, the review discusses drug development strategies for targeting key post-translational modification targets, such as agonists, inhibitors and PROTAC (proteolysis targeting chimaera) technology that targets E3 ubiquitin ligases.

The interactions between ineffective erythropoiesis and ferroptosis in ß-thalassemia.

In Guangxi, Hainan, and Fujian Province in southern China, ß-thalassemia is a frequent monogenic hereditary disorder that is primarily defined by hemolytic anemia brought on by inefficient erythropoiesis. It has been found that ineffective erythropoiesis in ß-thalassemia is closely associated with a high accumulation of Reactive oxygen species, a product of oxidative stress, in erythroid cells. During recent years, ferroptosis is an iron-dependent lipid peroxidation that involves abnormalities in lipid and iron metabolism as well as reactive oxygen species homeostasis. It is a recently identified kind of programmed cell death. ß-thalassemia patients experience increased iron release from reticuloendothelial cells and intestinal absorption of iron, ultimately resulting in iron overload. Additionally, the secretion of Hepcidin is inhibited in these patients. What counts is both ineffective erythropoiesis and ferroptosis in ß-thalassemia are intricately linked to the iron metabolism and Reactive oxygen species homeostasis. Consequently, to shed further light on the pathophysiology of ß-thalassemia and propose fresh ideas for its therapy, this paper reviews ferroptosis, ineffective erythropoiesis, and the way they interact.

Integrated profiling identifies ferredoxin 1 as an immune-related biomarker of malignant phenotype in glioma.

Background: Glioma, a highly resistant and recurrent type of central nervous system tumor, poses a significant challenge in terms of effective drug treatments and its associated mortality rates. Despite the discovery of Ferredoxin 1 (FDX1) as a crucial participant in cuproptosis, an innovative mechanism of cellular demise, its precise implications for glioma prognosis and tumor immune infiltration remain inadequately elucidated. Methods: To analyze pan-cancer data, we employed multiple public databases. Gene expression evaluation was performed using tissue microarray (TMA) and single-cell sequencing data. Furthermore, four different approaches were employed to assess the prognostic importance of FDX1 in glioma. We conducted the analysis of differential expression genes (DEGs) and Gene Set Enrichment Analysis (GSEA) to identify immune-related predictive signaling pathways. Somatic mutations were assessed using Tumor Mutation Burden (TMB) and waterfall plots. Immune cell infiltration was evaluated with five different algorithms. Furthermore, we performed in vitro investigations to evaluate the biological roles of FDX1 in glioma. Results: Glioma samples exhibited upregulation of FDX1, which in turn predicted poor prognosis and was positively associated with unfavorable clinicopathological characteristics. Notably, the top four enriched signaling pathways were immune-related, and the discovery revealed a connection between the expression of FDX1 and the frequency of mutations or the TMB. The FDX1_high group exhibited heightened infiltration of immune cells, and there existed a direct association between the expression of FDX1 and the regulation of immune checkpoint. In vitro experiments demonstrated that FDX1 knockdown reduced proliferation, migration, invasion and transition from G2 to M phase in glioma cells. Conclusion: In glioma, FDX1 demonstrated a positive association with the advancement of malignancy and changes in the infiltration of immune cells.

Causal associations between leisure sedentary behaviors and sleep status with frailty: insight from Mendelian randomization study.

BACKGROUND: Observational studies have suggested that sedentary behaviors and sleep status are associated with frailty. However, it remains unclear whether these associations are causal. METHODS: Using summary statistics from genome-wide association studies, we evaluated the causal effect of modifiable risk factors, including leisure sedentary behaviors and sleep status on the frailty index (FI) using two-sample univariable and multivariable Mendelian randomization (MR) analyses. Genetic correlations were tested between the correlated traits. RESULTS: We identified potential causal associations between the time spent watching television (ß = 0.26, 95% confidence interval [CI]: 0.21-0.31, P = 3.98e-25), sleep duration (ß = -0.18, 95%CI: -0.26, -0.10; P = 6.04e-06), and daytime napping (ß = 0.29, 95%CI: 0.18-0.41, P = 2.68e-07) and the FI based on the inverse-variance-weighted method. The estimates were consistent across robust and multivariate MR analyses. Linkage disequilibrium score regression detected a genetic correlation between the time spent watching television (Rg = 0.43, P = 6.46e-48), sleep duration (Rg = -0.20, P = 5.29e-10), and daytime napping (Rg = 0.25, P = 3.34e-21) and the FI. CONCLUSIONS: Genetic predispositions to time spent watching television and daytime napping were positively associated with the FI, while sleep duration was negatively associated with the FI. Our findings offer key insights into factors influencing biological aging and suggest areas for interventions to promote healthy aging and slow down the aging process.