Metabolic features of adolescent major depressive disorder: A comparative study between treatment-resistant depression and first-episode drug-naive depression.

Major depressive disorder (MDD) is a psychiatric illness that can jeopardize the normal growth and development of adolescents. Approximately 40% of adolescent patients with MDD exhibit resistance to conventional antidepressants, leading to the development of Treatment-Resistant Depression (TRD). TRD is associated with severe impairments in social functioning and learning ability and an elevated risk of suicide, thereby imposing an additional societal burden. In this study, we conducted plasma metabolomic analysis on 53 adolescents diagnosed with first-episode drug-naïve MDD (FEDN-MDD), 53 adolescents with TRD, and 56 healthy controls (HCs) using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) and reversed-phase liquid chromatography-mass spectrometry (RPLC-MS). We established a diagnostic model by identifying differentially expressed metabolites and applying cluster analysis, metabolic pathway analysis, and multivariate linear support vector machine (SVM) algorithms. Our findings suggest that adolescent TRD shares similarities with FEDN-MDD in five amino acid metabolic pathways and exhibits distinct metabolic characteristics, particularly tyrosine and glycerophospholipid metabolism. Furthermore, through multivariate receiver operating characteristic (ROC) analysis, we optimized the area under the curve (AUC) and achieved the highest predictive accuracy, obtaining an AUC of 0.903 when comparing FEDN-MDD patients with HCs and an AUC of 0.968 when comparing TRD patients with HCs. This study provides new evidence for the identification of adolescent TRD and sheds light on different pathophysiologies by delineating the distinct plasma metabolic profiles of adolescent TRD and FEDN-MDD.

The role of cyclin-dependent kinase inhibitor 3 in the proliferation and migration of renal cell carcinoma.

The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, is over expressed in renal cell carcinoma (RCC). However, the cell biology functions of RCC are not well understood. The present study aimed to verify the ability of CDKN3 to promote the proliferation and migration of RCC through in vitro experiments. Subsequently, the clinical prognostic effects were analyzed using The Cancer Genome Atlas (TCGA; https://www.cancer.gov/) and Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/). The chelators, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an analogue of the anti-tumor agent, were screened through bioinformatics analysis. The expression of CDKN3 is positively correlated with the IC50 of Dp44mT. In two RCC cell lines, 786-0 and Caki-1,we conducted small interfering RNA (siRNA) knockdown of CDKN3 and overexpression of CDKN3 by transfection plasmid. Subsequently, we administered Dp44mT to examine the resulting alterations in cell proliferation, migration, and apoptosis, thereby elucidating the role of CDKN3 and Dp44mT in these processes. The results of the experiment revealed a positive association between CDKN3 expression and the proliferation of RCC cell lines. Down-regulating CDKN3 significantly increased the apoptosis rate and inhibited cell migration in 786-0 and Caki-1 cells. Furthermore, bioinformatics analysis revealed a high expression of CDKN3 in RCC and a negative association between CDKN3 expression and survival. Gene set enrichment analysis (GSEA) revealed a significant association between high CDKN3 expression and the cell cycle pathway. Furthermore, we identified Dp44mT as a drug highly correlated with CDKN3 through the database. Subsequent addition of Dp44mT resulted in similar findings to those observed upon CDKN3 knockdown. Our findings have important implications for the diagnosis and treatment of CDKN3 in RCC. Additionally, Dp44mT is likely to be a promising candidate for future clinical applications.

Production of 17α-hydroxyprogesterone using an engineered biocatalyst with efficient electron transfer and improved 5-aminolevulinic acid synthesis coupled with a P450 hydroxylase.

17α-Hydroxyprogesterone (17α-OH-PROG) is an important intermediate with a wide range of applications in the pharmaceutical industry. Strategies based on efficient electron transfer and cofactor regeneration were used for the production of 17α-OH-PROG. Here, CYP260A1, Fpr and Adx were expressed using a double plasmid system, resulting in higher biotransformation efficiency. Further optimization of reaction conditions and addition of polymyxin B increased the production of 17α-OH-PROG from 12.52 mg/L to 102.37 mg/L after 12 h of biotransformation. To avoid the addition of external 5-aminolevulinic acid (ALA) as a heme precursor for the P450 enzyme, a modified C5 pathway was introduced into the engineered strain, further reducing the overall process cost. The resulting whole-cell biocatalyst achieved the highest biotransformation yield of 17α-OH-PROG reported to date, offering a promising strategy for commercial application of P450 enzymes in industrial production of hydroxylated intermediates.

GJA4 expressed on cancer associated fibroblasts (CAFs)-A 'promoter' of the mesenchymal phenotype.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. METHODS: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. RESULTS: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). CONCLUSION: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Phosphatidylserine and/or Sialic Acid Modified Liposomes Increase Uptake by Tumor-associated Macrophages and Enhance the Anti-tumor Effect.

DOX liposomes have better therapeutic effects and lower toxic side effects. The targeting ability of liposomes is one of the key factors affecting the therapeutic effect of DOX liposomes. This study developed two types of targeted liposomes. Sialic acid (SA)-modified liposomes were designed to target the highly expressed Siglec-1 receptor on tumor-associated macrophages surface. Phosphatidylserine (PS)-modified liposomes were designed to promote phagocytosis by monocyte-derived macrophages through PS apoptotic signaling. In order to assess and compare the therapeutic potential of different targeted pathways in the context of anti-tumor treatment, we compared four phosphatidylserine membrane materials (DOPS, DSPS, DPPS and DMPS) and found that liposomes prepared using DOPS as material could significantly improve the uptake ability of RAW264.7 cells for DOX liposomes. On this basis, normal DOX liposomes (CL-DOX) and SA-modified DOX liposomes (SAL-DOX), PS-modified DOX liposomes (PS-CL-DOX), SA and PS co-modified DOX liposomes (PS-SAL-DOX) were prepared. The anti-tumor cells function of each liposome on S180 and RAW264.7 in vitro was investigated, and it was found that SA on the surface of liposomes can increase the inhibitory effect. In vivo efficacy results exhibited that SAL-DOX and PS-CL-DOX were superior to other groups in terms of ability to inhibit tumor growth and tumor inhibition index, among which SAL-DOX had the best anti-tumor effect. Moreover, SAL-DOX group mice had high expression of IFN-γ as well as IL-12 factors, which could significantly inhibit mice tumor growth, improve the immune microenvironment of the tumor site, and have excellent targeted delivery potential.

Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase.

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

High Magnesium Promotes the Recovery of Binocular Vision from Amblyopia via TRPM7.

Abnormal visual experience during the critical period can cause deficits in visual function, such as amblyopia. High magnesium (Mg2+) supplementary can restore ocular dominance (OD) plasticity, which promotes the recovery of amblyopic eye acuity in adults. However, it remains unsolved whether Mg2+ could recover binocular vision in amblyopic adults and what the molecular mechanism is for the recovery. We found that in addition to the recovery of OD plasticity, binocular integration can be restored under the treatment of high Mg2+ in amblyopic mice. Behaviorally, Mg2+-treated amblyopic mice showed better depth perception. Moreover, the effect of high Mg2+ can be suppressed with transient receptor potential melastatin-like 7 (TRPM7) knockdown. Collectively, our results demonstrate that high Mg2+ could restore binocular visual functions from amblyopia. TRPM7 is required for the restoration of plasticity in the visual cortex after high Mg2+ treatment, which can provide possible clinical applications for future research and treatment of amblyopia.

Mendelian randomization analysis reveals causal relationships between circulating cell traits and renal disorders.

Purpose: The aim of this study was to investigate the causal relationships between circulating cell traits and risk of renal disorders. Methods: We applied a comprehensive two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) from publicly available genome-wide association studies (GWAS) databases were utilized. Genetically predicted instrumental variables of human blood cell traits were extracted from Blood Cell Consortium (BCX) while data on renal diseases was obtained from Finngen consortium. The primary MR analysis was conducted using the inverse variance weighted (IVW) method, with the weighted median (WM) and MR-Egger models used as additional methods. Sensitivity analyses, including MR-PRESSO, radial regression and MR-Egger intercept were conducted to detect outliers and assess horizontal pleiotropy. We further utilized the leave-one-out analysis to assess the robustness of the results. Causal associations were considered significant based on false rate correction (FDR), specifically when the IVW method provided a pFDR < 0.05. Results: Our results demonstrated that both white blood cell (WBC) count (OR = 1.50, 95% CI = 1.10-2.06, pFDR = 0.033, pIVW = 0.011) and lymphocyte count (OR = 1.50, 95% CI = 1.13-1.98, pFDR = 0.027, pIVW = 0.005) were causally associated with a higher risk of IgA nephropathy. Furthermore, WBC count was identified as a significant genetic risk factor for renal malignant neoplasms (OR = 1.23, 95% CI = 1.06-1.43, pFDR = 0.041, pIVW = 0.007). Additionally, an increased level of genetically predicted eosinophils was found to be causally associated with a higher risk of diabetic nephropathy (OR = 1.21, 95% CI = 1.08-1.36, pFDR = 0.007, pIVW = 0.001). No evidence of pleiotropy was determined. Conclusion: Our findings provide evidence of causal associations of circulating WBC count, lymphocyte count and IgA nephropathy, WBC count and renal malignant neoplasms, and eosinophil count and diabetic nephropathy. These results have the potential to contribute to the development of novel diagnostic options and therapeutic strategies for renal disorders.

Change of function and brain activity in patients of right spastic arm paralysis combined with aphasia after contralateral cervical seventh nerve transfer surgery.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

Mycorrhizal associations relate to stable convergence in plant-microbial competition for nitrogen absorption under high nitrogen conditions.

Nitrogen (N) immobilization (Nim, including microbial N assimilation) and plant N uptake (PNU) are the two most important pathways of N retention in soils. The ratio of Nim to PNU (hereafter Nim:PNU ratio) generally reflects the degree of N limitation for plant growth in terrestrial ecosystems. However, the key factors driving the pattern of Nim:PNU ratio across global ecosystems remain unclear. Here, using a global data set of 1018 observations from 184 studies, we examined the relative importance of mycorrhizal associations, climate, plant, and soil properties on the Nim:PNU ratio across terrestrial ecosystems. Our results show that mycorrhizal fungi type (arbuscular mycorrhizal (AM) or ectomycorrhizal (EM) fungi) in combination with soil inorganic N mainly explain the global variation in the Nim:PNU ratio in terrestrial ecosystems. In AM fungi-associated ecosystems, the relationship between Nim and PNU displays a weaker negative correlation (r = -.06, p < .001), whereas there is a stronger positive correlation (r = .25, p < .001) in EM fungi-associated ecosystems. Our meta-analysis thus suggests that the AM-associated plants display a weak interaction with soil microorganisms for N absorption, while EM-associated plants cooperate with soil microorganisms. Furthermore, we find that the Nim:PNU ratio for both AM- and EM-associated ecosystems gradually converge around a stable value (13.8 ± 0.5 for AM- and 12.1 ± 1.2 for EM-associated ecosystems) under high soil inorganic N conditions. Our findings highlight the dependence of plant-microbial interaction for N absorption on both plant mycorrhizal association and soil inorganic N, with the stable convergence of the Nim:PNU ratio under high soil N conditions.

Biomechanical evaluation of various rigid internal fixation modalities for condylar-base-associated multiple mandibular fractures: A finite element analysis.

Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.

Prediction of Cognitive Impairment Risk among Older Adults: A Machine-Learning Based Comparative Study and Model Development.

Detecting cognitive decline early in the older adults is crucial for effective intervention. This study, part of the Ma'anshan Healthy Aging Cohort Study, examined 2,288 participants with normal cognitive function. Forty-two potential predictors, including demographics, chronic diseases, lifestyle factors, and baseline cognitive function, were selected. The dataset was divided into training, validation, and test sets (60%, 20%, and 20%, respectively). Recursive feature elimination (RFE) and six machine learning algorithms were used for model development. Model performance was assessed using area under the curve (AUC), specificity, sensitivity, and accuracy. SHapley Additive exPlanations (SHAP) was applied for interpretability, revealing the top ten influential features: baseline MMSE, education, economic status, social activities, PSQI, BMI, SBP, DBP, IADL, and age. The Naïve Bayes (NB) algorithm-based model achieved an AUC of 0.820 (95% CI 0.773-0.887) on the test set, outperforming other algorithms. This model can help primary healthcare staff in community settings identify individuals at higher risk of cognitive impairment within three years among older adults.

Prophylactic Effects of n-Acethylcysteine on Inflammation-induced Depression-like Behaviors in Mice.

Depression, affecting individuals worldwide, is a prevalent mental disease, with an increasing incidence. Numerous studies have been conducted on depression, yet its pathogenesis remains elusive. Recent advancements in research indicate that disturbances in synaptic transmission, synaptic plasticity, and reduced neurotrophic factor expression significantly contribute to depression's pathogenesis. In our study, we utilized adult male C57BL/6J mice. Lipopolysaccharide (LPS) can induce both chronic and acute depression-like symptoms in mice, a widely used model for studying depression associated with inflammation. N-acetylcysteine (NAC) exhibits anti-inflammatory and ameliorative effects on depressive symptoms. This study sought to determine whether NAC use could mitigate inflammatory depressive behavior through the enhancement of synaptic transmission, synaptic plasticity, and increasing levels of brain-derived neurotrophic factor (BDNF). In this study, we discovered that in mice modeled with depression-like symptoms, the expression levels of dendrites, BDNF, and miniature excitatory postsynaptic potential (mEPSC) in glutamatergic neurons, as well as the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPARs) GluA1 and GluA2 subunits, were significantly decreased. These findings suggest an impairment in the synaptic transmission of glutamatergic neurons. Following treatment with NAC, the previously mentioned levels improved, indicating an enhancement in both synaptic transmission and synaptic plasticity. Our results suggest that NAC exerts a protective effect on mouse models of inflammatory depression, potentially through the enhancement of synaptic transmission and plasticity, as well as the restoration of neurotrophic factor expression. These findings offer vital animal experimental evidence supporting NAC's role in mitigating inflammatory depressive behaviors.

Interpretable machine learning based on CT-derived extracellular volume fraction to predict pathological grading of hepatocellular carcinoma.

PURPOSE: To develop a non-invasive auxiliary assessment method based on CT-derived extracellular volume (ECV) to predict the pathological grading (PG) of hepatocellular carcinoma (HCC). METHODS: The study retrospectively analyzed 238 patients who underwent HCC resection surgery between January 2013 and April 2023. Six machine learning algorithms were employed to construct predictive models for HCC PG: logistic regression, extreme gradient boosting, Light Gradient Boosting Machine (LightGBM), random forest, adaptive boosting, and Gaussian naive Bayes. Model performance was evaluated using receiver operating characteristic curve analysis, including area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and F1 score. Calibration plots were used for visual evaluation of model calibration. Clinical decision curve analysis was performed to assess potential clinical utility by calculating net benefit. RESULTS: 166 patients from Hospital A were allocated to the training set, while 72 patients from Hospital B (constituting 30.25% of the total sample) were assigned to the test set. The model achieved an AUC of 1.000 (95%CI: 1.000-1.000) in the training set and 0.927 (95%CI: 0.837-0.999) in the validation set, respectively. Ultimately, the model achieved an AUC of 0.909 (95%CI: 0.837-0.980) in the test set, with an accuracy of 0.778, sensitivity of 0.906, specificity of 0.789, negative predictive value of 0.556, and F1 score of 0.908. CONCLUSION: This study successfully developed and validated a non-invasive auxiliary assessment method based on CT-derived ECV to predict the HCC PG, providing important supplementary information for clinical decision-making.

Association of visceral adiposity index with hypertension (NHANES 2003-2018).

Objectives: This study focused on the association between visceral adiposity index (VAI) and the prevalence of hypertension in a nationally representative population of American adults. Methods: The study obtained data from the National Health and Nutrition Examination Survey (NHANES) database from 2003-2018 for a large-scale study. This study incorporated participants ≥18 years of age. Multivariate logistic regression modelling and smoothed curve fitting were applied to investigate the existence of a correlation between VAI and hypertension prevalence. Subgroups were analyzed to confirm the stationarity of the association between VAI and hypertension prevalence. In addition, an interaction test was conducted in this study. Results: In completely adapted sequential models, the risk of hypertension prevalence in the overall population increased 0.17-fold with each 1-unit increase in VAI [odds ratio (OR) = 1.17; 95% confidence interval (CI) 1.12-1.22]. In the wholly adapted categorical model, there was a 0.95-fold increased risk of hypertension in the population of VAI quartile 4 (Q4) vs. VAI quartile 1 (Q1) (OR = 1.95; 95% CI 1.62-2.35). These results indicate that VAI was strongly related to the occurrence of hypertension, and smoothed curve-fitting analysis showed nonlinearity. Adjustment for covariates revealed no apparent interactions in the subgroup analyses, and results were stable across subgroups. Conclusion: This cross-sectional study suggests a nonlinear and positive correlation between elevated VAI and the adult risk of developing hypertension in U.S. adults.

Risk factors for hemorrhagic cystitis in children undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis.

BACKGROUND: The risk factors for hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT) are unclear. Therefore, we conducted this systematic review and meta-analysis to investigate the risk factors for HC in children undergoing HSCT. METHODS: We performed this meta-analysis by retrieving studies from PubMed, EMBASE, and the Cochrane Library up to October 10, 2023, and analyzing those that met the inclusion criteria. I2 statistics were used to evaluate heterogeneity. RESULTS: Twelve studies, including 2,764 patients, were analyzed. Male sex (odds ratio [OR] = 1.52; 95% confidence interval [CI], 1.16-2.00; p = 0.003, I2 = 0%), allogeneic donor (OR = 5.28; 95% CI, 2.60-10.74; p < 0.00001, I2 = 0%), human leukocyte antigen (HLA) mismatched donor (OR = 1.86; 95% CI, 1.00-3.44; p = 0.05, I2 = 31%), unrelated donor (OR = 1.58; 95% CI, 1.10-2.28; p = 0.01, I2 = 1%), myeloablative conditioning (MAC) (OR = 3.17; 95% CI, 1.26-7.97; p = 0.01, I2 = 0%), busulfan (OR = 2.18; 95% CI, 1.33-3.58; p = 0.002, I2 = 0%) or anti-thymoglobulin (OR = 1.65; 95% CI, 1.07-2.54; p = 0.02, I2 = 16%) use, and cytomegalovirus (CMV) reactivation (OR = 2.64; 95% CI, 1.44-4.82; p = 0.002, I2 = 0%) were risk factors for HC in children undergoing HSCT. CONCLUSIONS: Male sex, allogeneic donor, HLA-mismatched, unrelated donor, MAC, use of busulfan or anti-thymoglobulin, and CMV reactivation are risk factors for HC in children undergoing HSCT.

Inhibition and disaggregation effect of flavonoid-derived carbonized polymer dots on protein amyloid aggregation.

In this research, four water-insoluble flavonoid compounds were utilized and reacted with arginine to prepare four carbonized polymer dots with good water-solubility in a hydrothermal reactor. Structural characterization demonstrated that the prepared carbonized polymer dots were classic core-shell structure. Effect of the prepared carbonized polymer dots on protein amyloid aggregation was further investigated using hen egg white lysozyme and human lysozyme as model protein in aqueous solution. All of the prepared carbonized polymer dots could retard the amyloid aggregation of hen egg white lysozyme and human lysozyme in a dose-depended manner. All measurements displayed that the inhibition ratio of luteolin-derived carbonized polymer dots (CPDs-1) was higher than that of the other three carbonized polymer dots under the same dosage. This result may be interpreted by the highest content of phenolic hydroxyl groups on the periphery. The inhibition ratio of CPDs-1 on hen egg white lysozyme and human lysozyme reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 also could disaggregate the formed mature amyloid fibrils into short aggregates.

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer: Integrating Bioinformatics Analysis with Experimental Confirmation.

OBJECTIVE: To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS: We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS: We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION: Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.

Tuning Surface Organic Structures by Small Gas Molecules through Catassembly and Coassembly.

The field of molecular assembly has seen remarkable advancements across various domains, such as materials science, nanotechnology, and biomedicine. Small gas molecules serve as pivotal modulators, capable of altering the architecture of assemblies via tuning a spectrum of intermolecular forces including hydrogen bonding, dipole-dipole interactions, and metal coordination. Surface techniques, notably scanning tunneling microscopy and atomic force microscopy, have proven instrumental in dissecting the structural metamorphosis and characteristic features of these assemblies at an unparalleled single-molecule resolution. Recent research has spotlighted two innovative approaches for modulating surface molecular assemblies with the aid of small gas molecules: "catassembly" and "coassembly". This Perspective delves into these methodologies through the lens of varying molecular interaction types. The strategies discussed here for regulating molecular assembly structures using small gas molecules can aid in understanding various complex assembly processes and structures and provide guidance for the further fabrication of complex surface structures.