Genetic analysis of a novel FBN1 mutation in a pediatric Marfan syndrome patient.

The aim of this study was to investigate a novel FBN1 gene mutation in a pediatric patient with Marfan syndrome (MFS) to provide a theoretical basis for genetic counseling. The subject was a 5-month-old male infant. With informed consent from the proband and his family, 2 mL of peripheral venous blood was collected from the patient, his father, mother, and sister. DNA was extracted using a DNA extraction kit with EDTA-K as an anticoagulant. The extracted DNA was subjected to minigene transcription and bioinformatics analysis. For minigene construction, wild-type and mutant minigenes were inserted into pcMINI and pcMINI-C vectors, respectively. Four recombinant vectors were transfected into the HeLa and 293T cell lines. After transfection for 48 hours, RNA was extracted from eight samples. DNA was also extracted from the family members' samples to construct a library. Target regions were captured using the SureSelect Human All Exon V6 (Agilent) kit and were sequenced with Illumina NovaSeq (sequencing read length 2×150 bp). Bioinformatic analysis identified the c.8226+5del mutation as a variant of uncertain clinical significance (VOUS). Literature and database reviews confirmed that this mutation had not been previously reported, identifying it as a novel mutation. The study identified a novel FBN1 mutation, c.8226+5del, that may be associated with clinical features such as low-set ears and distinctive facial characteristics in the proband. This mutation likely affects normal mRNA splicing, altering the structure and function of Exon 64 and potentially contributing to the development of autosomal dominant MFS.

Machine learning models to predict osteonecrosis in patients with femoral neck fractures undergoing internal fixation.

OBJECTIVE: This study aimed to use machine learning (ML) to establish risk factor and prediction models of osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures (FNFs) after internal fixation. METHODS: We retrospectively collected clinical data of patients with FNFs who were followed up for at least 2 years. Only intracapsular FNFs were included. In total, 437 patients and 24 variables were enrolled. The entire dataset was divided into training (89.5 %) and test (10.5 %) datasets. Six models-logistic regression, naive Bayes, decision tree, random forest, multilayer perceptron, and AdaBoost-were established and validated for predicting postoperative ONFH. We compared the area under the receiver operating characteristic curve (AUC), accuracy, recall, and F1 score of different models. In addition, a confusion matrix, density curve, and learning curve were used to evaluate the model performance. RESULTS: The logistic regression model performed best at predicting ONFH in patients with FNFs undergoing internal fixation surgery, with an AUC, accuracy, recall, F1 score, and prediction value of 0.84, 0.89, 1.00, 0.94, and 89.1 %, respectively. The learning and density curves demonstrated a good prediction fitting degree and distinct separation. When establishing the ML models, the reduction quality, internal fixation removal, American Society of Anesthesiologists classification, injury mechanism, and displacement distance of the medial cortex were the top five risk factors positively correlated with the occurrence of ONFH. CONCLUSIONS: The logistic regression model had excellent performance in predicting ONFH in patients with FNFs after internal fixation and could provide valuable guidance in clinical decision-making. When choosing treatment options for patients with FNFs, doctors should identify the risk factors and consider using the presented models to help anticipate outcomes and select individualised treatment.

Amorphous Titanium Dioxide-Based Heterojunction with Locally Enhanced Electron Transport Multipathways for High-Efficient Photodegradation of Tetracycline.

A novel amorphous titanium dioxide (AT)-based heterojunction, composed of AT, silver bromide, and silver nanoparticles (Ag NPs), was synthesized and designated as AgBr/Ag/AT-4%. The band structure and active species of AgBr/Ag/AT-4% composites were investigated, and the existence of multiple electron transport pathways in the composites was determined. The Channel I is an all-solid-state Z-scheme heterostructure formed between AT and AgBr by Ag acting as an electron transport bridge, and Channel II is excited by the localized surface plasmon resonance effect induced by the Ag NPs on the photocatalyst surface. The Channel III is an electronically bridged medium with Ti3+/Ti4+ redox coupling pairs and oxygen vacancy-mediated trap states constructed from defective structures. The activity of the sample was assessed by the photocatalytic degradation of tetracycline. It is hoped that this work will provide a new idea for the preparation of an amorphous titanium dioxide-based heterojunction with locally enhanced electron transport multiple pathways.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

Theaflavins mitigate diabetic symptoms in GK rats by modulating the INSR/PI3K-Akt/GSK-3 pathway and intestinal microbiota.

Dietary management and interventions are crucial in the clinical management of diabetes. Numerous active dietary components in black tea have demonstrated positive effects on blood glucose levels and metabolic functions. However, limited research has explored the potential of theaflavins (TF), polyphenols in black tea, for diabetes management. In this study, high-purity TF was administered to Goto-Kakizaki (GK) diabetic model rats for four weeks to investigate its impact on diabetic pathology and analyze the underlying mechanisms through liver transcriptomics, hepatocyte metabolomics, and gut microbiome analysis. The findings indicated that continuous administration of TF (100 mg/kg) significantly suppressed blood glucose levels, reduced insulin resistance, and decreased the expression of oxidative stress indicators and inflammatory factors in GK rats. Further analysis revealed that TF might alleviate insulin resistance by improving hepatic glycogen conversion and reducing hepatic lipid deposition through modulation of key pathways, such as peroxisome proliferator-activated receptors and PI3K/AKT/GSK-3 pathways within the liver, thereby ameliorating diabetic symptoms. Additionally, TF intake facilitated the restoration of the intestinal microbial community structure by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. It also reduced endotoxin lipopolysaccharide production, thereby lowering the chances of insulin resistance development and enhancing its efficacy in regulating blood glucose levels. These findings offer a novel perspective on the potential of black tea and its active constituents to prevent and treat diabetes and other metabolic disorders, providing valuable references for identifying and applying active dietary components from tea.

The traditional Chinese medicine Qiliqiangxin in heart failure with reduced ejection fraction: a randomized, double-blind, placebo-controlled trial.

Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .

Comparison of different immobilisation durations following open surgery for acute achilles tendon rupture: a prospective cohort study.

BACKGROUND: In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. METHODS: This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. RESULTS: The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P < 0.001). The VAS scores decreased over time, reaching 0 in all groups by 10 weeks. The mean scores in groups A and B were higher than those in the other groups at 2 and 4 weeks (P < 0.001), whereas the opposite was true at 8 weeks (P < 0.001). ATRS and the AOFAS Ankle-Hindfoot scale score increased across all groups over time, showing significant between-group differences from weeks 6 to 16 (P < 0.001) and weeks 6 to 12 (P < 0.001). The mean scores were better in groups A and B than in groups C and D. Thirty-eight complications (3.5%) were observed, including 20 re-ruptures and 18 superficial infections. All complications were resolved at the last follow-up, with no significant between-group differences. CONCLUSIONS: Immobilisation for 2 weeks after open surgery for ATR repair may be the optimal strategy for early rehabilitation with relatively minimal pain and other complications. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04663542).

Highly efficient recovery of phosphate and fluoride from phosphogypsum leachate: Selective precipitation and adsorption.

Phosphogypsum, a typical by-product in the phosphorus chemical industry, could generate a large amount of leachate containing phosphate and fluoride in the process of rainfall and long-term stacking, which not only causes serious environmental pollution, but also leads to a waste of resources. In this study, a united treatment of calcium hydroxide precipitation and lanthanum zeolite (La-ZFA) adsorption was proposed to achieve the recovery of phosphate and fluoride from phosphogypsum leachate. In phosphogypsum, most phosphorus could be leached except P in the residual occurrence form, while for fluoride, only water-soluble F could be effectively leached. The optimum leaching amounts of phosphate and fluoride were 22.59 and 4.64 mg/g, respectively, at liquid-solid ratio of 400:1, leaching time of 120 min, pH of 6.0, particle size of >200 mesh (<0.075 mm), and leaching temperature of 25°C. Using Ca(OH)2 as the precipitant, the phosphate could be precipitated selectively from phosphogypsum leachate by controlling pH and time, and the concentrations of it decreased significantly to 0.29 mg/L at pH 10.0, with a removal efficiency of 99.48%. XRD, SEM and Visual MINTEQ software analysis proved that the main component of the precipitate was hydroxyapatite (Ca5(PO4)3(OH)). After P precipitation, a series of sorbents for fluoride were investigated, and La-ZFA sorbent was chosen and utilized to recover the fluoride from the leachate through a cyclic fixed-bed column. The efficiency of La-ZFA was basically not affected by the high concentration sulfate, and it can selectively adsorb fluoride from phosphogypsum leachate, leading to a final fluoride concentration of 0.29 mg/L in the effluent. The characterization demonstrated that fluoride might be adsorbed onto the La-ZFA via ligand exchange with hydroxy groups. The proposed method in this study is expected to sequentially recover phosphate and fluorine from the leachate of phosphogypsum, and it has great guiding significance for resource utilization and management of phosphogypsum.

Presentation and management of marantic endocarditis: A case series.

Marantic endocarditis is defined as a sterile endocarditis that is rarely encountered in clinical practice. This case series illustrates five cases of marantic endocarditis. All cases were diagnosed on trans thoracic echocardiography and verified on transesophageal echocardiography. The first three cases occur in the setting of antiphospholipid syndrome; the last two occur in the setting of advanced malignancy. Two cases were treated successfully with anticoagulation, while two others required valvular surgery. One case resulted in mortality. The treatment course of these five patients mirrors certain patterns described in the literature.

Overexpression of sesame O-acetylserine(thiol)lyase induces male sterility by delaying tapetum programmed cell death.

Male sterile lines are key resources for hybrid seed production and for ensuring high varietal purity. However, the genes and mechanisms underlying sesame male sterility remain largely unknown. Hence, this study identified an O-acetylserine(thiol)lyase gene SiOASTL1 and functionally characterized its roles in inducing defective anther development. Spatiotemporal expression analysis revealed that SiOASTL1 is significantly (2.7 fold) up-regulated in sterile sesame anthers at the microspore stage compared with fertile ones. Sequence and phylogenetic analyses showed that SiOASTL1 is homologous to Arabidopsis OAS-TL plastid isoforms. We thus overexpressed SiOASTL1 in Arabidopsis to unravel its regulatory roles. Cytological observation revealed that SiOASTL1 overexpression transformed transgenic plants into male sterile lines arising at the microspore development stage. SiOASTL1 overexpression decreased cysteine biosynthesis and down-regulated the expression of the sporopollenin synthesis-related genes, including AtTKPR1, AtTKPR2, AtPKSA, and AtPKSB in transgenic Arabidopsis. Consequently, the tapetum programmed cell death (PCD) was delayed, resulting in the formation of defective pollen grains with irregular walls and empty cytoplasm. Our findings prove that the induction of SiOASTL1 expression disrupts pollen development and contributes to sesame male sterility. Moreover, these results suggest that genetic manipulation of SiOASTL1 expression may facilitate the development of new hybrid varieties in sesame and other crops.

Metformin relieves bone cancer pain by reducing TGFßRI-TRPV1 signaling in rats.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFß1 in the metastatic bone tissue, and raised the expression of TGFßRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFßRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFß1, TGFßRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFß1-TGFßRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) (Milan IVB) and Its Subgroups: A Multi-Institutional Analysis of Risk of Neoplasm and Malignancy.

OBJECTIVES: Fine needle aspiration (FNA) plays a crucial role in their initial assessment of salivary gland neoplasms. In the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the category of Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP) categorizes lesions with ambiguous features. This study aims to investigate the risk of neoplasm (RON) and risk of malignancy (ROM) within different subgroups of SUMP lesions using data from three large academic institutions. METHODS: We analyzed salivary gland (FNA) cases from three academic institutions post-MSRSGC implementation. Salivary gland FNA cases categorized as Milan IVB (SUMP) with subsequent surgical pathology follow-up were analyzed. Cases were divided into basaloid, oncocytic, and clear cell SUMP subtypes, with RON and ROM assessed and compared. RESULTS: Out of 1377 MSRSGC cases, 231 were SUMP (16.8%), with 101 subjected to surgical pathology follow-up. The overall ROM for SUMP was 20.8%, with variations of 10% to 29.5% observed amongst institutions, but no significant difference was observed among three institutions (p = 0.15). Basaloid and oncocytic SUMP displayed 17.1% and 20.5% ROM, respectively, without significant disparity. However, all clear cell SUMP cases were malignant on surgical resection. CONCLUSIONS: This study highlights the variability in ROM for SUMP lesions and the significantly higher ROM in SUMP cases with clear cell features. These findings emphasize the importance of accurately subcategorizing SUMP lesions, particularly those with clear cell features, for appropriate clinical management.

Liquid-liquid phase separation is essential for reovirus viroplasm formation and immune evasion.

Grass carp reovirus (GCRV) is the most virulent pathogen in the genus Aquareovirus, belonging to the family Spinareoviridae. Members of the Spinareoviridae family are known to replicate and assemble in cytoplasmic inclusion bodies termed viroplasms; however, the detailed mechanism underlying GCRV viroplasm formation and its specific roles in virus infection remains largely unknown. Here, we demonstrate that GCRV viroplasms form through liquid-liquid phase separation (LLPS) of the nonstructural protein NS80 and elucidate the specific role of LLPS during reovirus infection and immune evasion. We observe that viroplasms coalesce within the cytoplasm of GCRV-infected cells. Immunofluorescence and transmission electron microscopy indicate that GCRV viroplasms are membraneless structures. Live-cell imaging and fluorescence recovery after photobleaching assay reveal that GCRV viroplasms exhibit liquid-like properties and are highly dynamic structures undergoing fusion and fission. Furthermore, by using a reagent to inhibit the LLPS process and constructing an NS80 mutant defective in LLPS, we confirm that the liquid-like properties of viroplasms are essential for recruiting viral dsRNA, viral RdRp, and viral proteins to participate in viral genome replication and virion assembly, as well as for sequestering host antiviral factors for immune evasion. Collectively, our findings provide detailed insights into reovirus viroplasm formation and reveal the specific functions of LLPS during virus infection and immune evasion, identifying potential targets for the prevention and control of this virus. IMPORTANCE: Grass carp reovirus (GCRV) poses a significant threat to the aquaculture industry, particularly in China, where grass carp is a vital commercial fish species. However, detailed information regarding how GCRV viroplasms form and their specific roles in GCRV infection remains largely unknown. We discovered that GCRV viroplasms exhibit liquid-like properties and are formed through a physico-chemical biological phenomenon known as liquid-liquid phase separation (LLPS), primarily driven by the nonstructural protein NS80. Furthermore, we confirmed that the liquid-like properties of viroplasms are essential for virus replication, assembly, and immune evasion. Our study not only contributes to a deeper understanding of GCRV infection but also sheds light on broader aspects of viroplasm biology. Given that viroplasms are a universal feature of reovirus infection, inhibiting LLPS and then blocking viroplasms formation may serve as a potential pan-reovirus inhibition strategy.

Heterotrophic nitrification processes driven by glucose and sodium acetate: New insights into microbial communities, functional genes and nitrogen metabolism from metagenomics and metabolomics.

Heterotrophic nitrification (HN) bacteria use organic carbon sources to remove ammonia nitrogen (NH4+-N); however, the mechanisms of carbon and nitrogen metabolism are unknown. To understand this mechanism, HN functional microbial communities named MG and MA were enriched with glucose and sodium acetate, respectively. The NH4+-N removal efficiencies were 98.87 % and 98.91 %, with 88.06 % and 69.77 % nitrogen assimilation for MG and MA at 22 h and 10 h, respectively. Fungi (52.86 %) were more competitive in MG, and bacteria (99.99 %) were dominant in MA. Metagenomic and metabolomic analyses indicated that HN might be a signaling molecule (NO) in the production and detoxification processes when MG metabolizes glucose (amo, hao, and nosZ were not detected). MA metabolizes sodium acetate to produce less energy and promotes nitrogen oxidation reduction; however, genes (hao, hox, and NOS2) were not detected. These results suggest that NO and energy requirements induce microbial HN.

Effects of 2,4,6-Trichloroanisole on the morphological development and motility of zebrafish.

2,4,6-Trichloroanisole (2,4,6-TCA), a compound with a characteristic earthy odor, is a common source of odorous pollutants in drinking water and wine. However, research on its biological toxicity is limited. In this study, we used zebrafish as an indicator model to investigate the effects of 2,4,6-TCA exposure on morphological development, oxidative stress, apoptosis, heart rate, blood flow, and motility. We found that exposure to 2,4,6-TCA resulted in significant spinal, tail, and cardiac deformities in zebrafish larvae and promoted a pronounced oxidative stress response and extensive cell apoptosis, notably in the digestive tract, head, spine, and heart, ultimately leading to significant reductions in zebrafish heart rate, blood flow, and motility. Moreover, these effects became more pronounced with an increase in the concentration of 2,4,6-TCA to which the zebrafish were exposed. Furthermore, qPCR analysis revealed that exposure to 2,4,6-TCA promoted significant changes in the expression levels of genes associated with oxidative stress, apoptosis, cardiac development, and the nervous system, particularly key genes (p53, apaf1, casp9, and casp3) in the mitochondrial apoptotic pathway, which were significantly upregulated. Similarly, we detected significant upregulation of ache gene expression. These findings indicated that exposure to 2,4,6-TCA resulted in the accumulation of reactive oxygen species in zebrafish, induced strong oxidative stress responses, and triggered lipid peroxidation and extensive cell apoptosis. Cellular apoptosis, which mitochondrial signaling pathways may mediate, has been found to lead to malformations in zebrafish embryos, resulting in significant reductions in cardiac function and motility. To our knowledge, this is the first systematic assessment of the toxicity of 2,4,6-TCA, and our findings provide an important reference for risk assessment and early warning of 2,4,6-TCA exposure.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Characterization of the CsCENH3 protein and centromeric DNA profiles reveal the structures of centromeres in cucumber.

Centromeres in eukaryotes mediate the accurate segregation of chromosomes during cell division. They serve as essential functional units of chromosomes and play a core role in the process of genome evolution. Centromeres are composed of satellite repeats and highly repetitive centromeric retrotransposons (CRs), which vary greatly even among closely related species. Cucumber (Cucumis sativus) is a globally cultivated and economically important vegetable and the only species in the Cucumis genus with seven pairs of chromosomes. Therefore, studying the centromeres of the Cucumis subgenus may yield valuable insights into its genome structure and evolution. Using chromatin immunoprecipitation (ChIP) techniques, we isolated centromeric DNA from cucumber reference line 9930. Our investigation into cucumber centromeres uncovered the centromeric satellite sequence, designated as CentCs, and the prevalence of Ty1/Copia long terminal repeat retrotransposons. In addition, active genes were identified in the CsCENH3 nucleosome regions with low transcription levels. To the best of our knowledge, this is the first time that characterization of centromeres has been achieved in cucumber. Meanwhile, our results on the distribution of CentCs and CsCRs in the subgenus Cucumis indicate that the content of centromeric repeats in the wild variants was significantly reduced compared with the cultivated cucumber. The results provide evidence for centromeric DNA amplification that occurred during the domestication process from wild to cultivated cucumber. Furthermore, these findings may offer new information for enhancing our understanding of phylogenetic relationships in the Cucumis genus.

N6-methyladenosine methylation regulates the tumor microenvironment of Epstein-Barr virus-associated gastric cancer.

BACKGROUND: N6-methyladenosine (m6A) methylation modification exists in Epstein-Barr virus (EBV) primary infection, latency, and lytic reactivation. It also modifies EBV latent genes and lytic genes. EBV-associated gastric cancer (EBVaGC) is a distinctive molecular subtype of GC. We hypothesized EBV and m6A methylation regulators interact with each other in EBVaGC to differentiate it from other types of GC. AIM: To investigate the mechanisms of m6A methylation regulators in EBVaGC to determine the differentiating factors from other types of GC. METHODS: First, The Cancer Gene Atlas and Gene Expression Omnibus databases were used to analyze the expression pattern of m6A methylation regulators between EBVaGC and EBV-negative GC (EBVnGC). Second, we identified Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment of m6A-related differentially expressed genes. We quantified the relative abundance of immune cells and inflammatory factors in the tumor microenvironment (TME). Finally, cell counting kit-8 cell proliferation test, transwell test, and flow cytometry were used to verify the effect of insulin-like growth factor binding protein 1 (IGFBP1) in EBVaGC cell lines. RESULTS: m6A methylation regulators were involved in the occurrence and development of EBVaGC. Compared with EBVnGC, the expression levels of m6A methylation regulators Wilms tumor 1-associated protein, RNA binding motif protein 15B, CBL proto-oncogene like 1, leucine rich pentatricopeptide repeat containing, heterogeneous nuclear ribonucleoprotein A2B1, IGFBP1, and insulin-like growth factor 2 binding protein 1 were significantly downregulated in EBVaGC (P < 0.05). The overall survival rate of EBVaGC patients with a lower expression level of IGFBP1 was significantly higher (P = 0.046). GO and KEGG functional enrichment analyses showed that the immunity pathways were significantly activated and rich in immune cell infiltration in EBVaGC. Compared with EBVnGC, the infiltration of activated CD4+ T cells, activated CD8+ T cells, monocytes, activated dendritic cells, and plasmacytoid dendritic cells were significantly upregulated in EBVaGC (P < 0.001). In EBVaGC, the expression level of proinflammatory factors interleukin (IL)-17, IL-21, and interferon-γ and immunosuppressive factor IL-10 were significantly increased (P < 0.05). In vitro experiments demonstrated that the expression level of IGFBP1 was significantly lower in an EBVaGC cell line (SNU719) than in an EBVnGC cell line (AGS) (P < 0.05). IGFBP1 overexpression significantly attenuated proliferation and migration and promoted the apoptosis levels in SNU719. Interfering IGFBP1 significantly promoted proliferation and migration and attenuated the apoptosis levels in AGS. CONCLUSION: m6A regulators could remodel the TME of EBVaGC, which is classified as an immune-inflamed phenotype and referred to as a "hot" tumor. Among these regulators, we demonstrated that IGFBP1 affected proliferation, migration, and apoptosis.

Effect of capsule treatment on visual acuity and quality after phacoemulsification lens implantation in myopic patients with cataract.

BACKGROUND: Cataracts pose a significant clinical burden due to their complex pathogenesis. In recent years, an increase in cataracts coexisting with myopia has heightened the incidence of retinopathy and posterior vitreous detachment. Additionally, symptoms of ocular axis elongation, lens nucleus hardening, and vitreous liquefaction have become more prevalent. While conventional extracapsular cataract extraction is commonly employed, it often yields suboptimal visual outcomes. Subsequent advancements in cataract phacoemulsification and lens implantation surgeries have gained widespread acceptance for their ability to improve refraction and significantly improve uncorrected visual acuity. AIM: To investigate the effect of capsular treatment after phacoemulsification lens implantation in myopic patients with cataract. METHODS: We selected 110 patients (with 134 eyes) with myopia and cataracts treated. These patients were categorized into two groups: an observation group (57 patients with 70 eyes) and a control group (53 patients with 64 eyes). The control group underwent cataract phacoemulsification and lens implantation, while the observation group received a refined capsular treatment based on the control group's procedure. We assessed the differences in visual acuity and quality between the two groups before and after surgery. RESULTS: At six months post-operation, the observation group exhibited significantly improved far vision, intermediate vision, near vision, lower objective scattering index, higher Modulation transfer function cut-off frequency, and overall vision metrics at different contrast levels (100%, 20% and 9%) compared to the control group (P < 0.05). The total score of the National Eye Institute Visual Function Questionnaire in the observation group at 6 months after operation was significantly higher than that in the control group (P < 0.05). No significant difference in the incidence of adverse reactions was observed between the observation group and control group (P > 0.05). CONCLUSION: Capsular treatment demonstrates efficacy in improving visual acuity and quality after phacoemulsification lens implantation in myopic patients with cataracts, warranting its clinical application.