Clinical analysis of acute poisoning in children.

OBJECTIVE: The clinical characteristics of hospitalized children with acute poisoning were analyzed to provide a reference for preventing poisoning and seeking effective prevention and treatment. METHODS: The clinical data of 112 children with acute poisoning admitted to Qilu Hospital of Shandong University from January 1, 2018, to December 31, 2021, were collected and analyzed from different perspectives. RESULTS: The majority of acute poisoning cases that occurred in children were in early childhood and preschool age (89 cases, accounting for 79.4%). The most common types of poisoning were pesticide poisoning and drug poisoning, and the main ways of poisoning were accidental administration via the digestive tract and accidental ingestion. Poisoning occurred slightly more in spring and summer all year round, and most children had a good prognosis after timely treatment. CONCLUSION: Acute poisoning often occurs in children. Parental education and intensified child supervision are needed to prevent the incidence of unintentional poisoning.

High HSPB1 expression predicts poor clinical outcomes and correlates with breast cancer metastasis.

BACKGROUND: Heat shock protein beta-1 (HSPB1) is a crucial biomarker for pathological processes in various cancers. However, the clinical value and function of HSPB1 in breast cancer has not been extensively explored. Therefore, we adopted a systematic and comprehensive approach to investigate the correlation between HSPB1 expression and clinicopathological features of breast cancer, as well as determine its prognostic value. We also examined the effects of HSPB1 on cell proliferation, invasion, apoptosis, and metastasis. METHODS: We investigated the expression of HSPB1 in patients with breast cancer using The Cancer Genome Atlas and immunohistochemistry. Chi-squared test and Wilcoxon signed-rank test were used to examine the relationship between HSPB1 expression and clinicopathological characteristics. RESULTS: We observed that HSPB1 expression was significantly correlated with the stage N, pathologic stages, as well as estrogen and progesterone receptors. Furthermore, high HSPB1 expression resulted in a poor prognosis for overall survival, relapse-free survival, and distant metastasis-free survival. Multivariable analysis showed that patients with poor survival outcomes had higher tumor, node, metastasis, and pathologic stages. Pathway analysis of HSPB1 and the altered neighboring genes suggested that HSPB1 is involved in the epithelial-to-mesenchymal transition. Functional analysis revealed showed that transient knockdown of HSPB1 inhibited the cell migration/invasion ability and promoted apoptosis. CONCLUSIONS: HSPB1 may be involved in breast cancer metastasis. Collectively, our study demonstrated that HSPB1 has prognostic value for clinical outcomes and may serve as a therapeutic biomarker for breast cancer.

Pretreatment drug resistance in people living with HIV: A large retrospective cohort study in Chongqing, China.

OBJECTIVES: The emergence of pretreatment drug resistance (PDR) caused by increased usage of antiretroviral therapy (ART) represents a significant challenge to HIV management. In this study, we evaluated the prevalence of PDR in people living with HIV (PLWH) in Chongqing, China. METHODS: We retrospectively collected the data of 1110 ART-naïve PLWH in Chongqing from January 1, 2018 to June 30, 2021. HIV-1 genotypes and drug resistance were analyzed using the HIV-1 pol sequence. Risk factors associated with PDR were evaluated via the logistic regression model. RESULTS: Nine genotypes were detected among 1110 participants, with CRF07_BC (55.68%) being the dominant genotype, followed by CRF01_AE (21.44%), CRF08_BC (14.14%), and other genotypes (8.74%). Of all the participants, 24.14% exhibited drug resistance mutations (DRMs). The predominant DRMs for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) were V179D/E/A/DIN (13.60%) and M184V/I (1.44%), respectively, whereas only two major DRMs (M46L and I54L) were identified for protease inhibitors (PIs). The total prevalence of PDR was 10.54%, with 2.43%, 7.66%, and 1.71% participants exhibiting PDR to NRTIs, NNRTIs, and PIs, respectively. Furthermore, female PLWH, delays in ART initiation, and the CRF08_BC genotype were associated with a higher risk of PDR. CONCLUSIONS: Our study provides the first large cohort data on the prevalence of PDR in Chongqing, China. HIV-1 genotypes are diverse and complex, with a moderate level of PDR, which does not reach the threshold for the initiation of a public health response. Nevertheless, continuous surveillance of PDR is both useful and advisable.

Predictive value of protease-activated receptor-2 (PAR2 ) in cervical cancer metastasis.

Metastasis is the primary cause of an unfavourable prognosis in patients with malignant cancer. Over the last decade, the role of proteinases in the tumour microenvironment has attracted increasing attention. As a sensor of proteinases, proteinase-activated receptor 2 (PAR2 ) plays crucial roles in the metastatic progression of cervical cancer. In the present study, the expression of PAR2 in multiple types of cancer was analysed by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier plotter was used to calculate the correlation between survival and the levels of PAR2 , Grb-associated binding protein 2(Gab2) and miR-125b. Immunohistochemistry (IHC) was performed to examine PAR2 expression in a tissue microarray (TMA) of CESCs. Empower Stats was used to assess the predictive value of PAR2 in the metastatic potential of CESC. We found that PAR2 up-regulation was observed in multiple types of cancer. Moreover, PAR2 expression was positively correlated with the clinicopathologic characteristics of CESC. miR-125b and its target Gab2, which are strongly associated with PAR2 -induced cell migration, are well-characterized as predictors of the prognostic value of CESC. Most importantly, the Cancer Genome Atlas (TCGA) data set analysis showed that the area under the curve (AUC) of the PAR2 model was significantly greater than that of the traditional model (0.833 vs 0.790, P < .05), demonstrating the predictive value of PAR2 in CESC metastasis. Our results suggest that PAR2 may serve as a prognostic factor for metastasis in CESC patients.

VWCE as a potential biomarker associated with immune infiltrates in breast cancer.

PURPOSE: Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. METHODS: The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. RESULTS: The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = - 0.12, p = 6e-05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. CONCLUSIONS: In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

SCUBE3 serves as an independent poor prognostic factor in breast cancer.

BACKGROUND: Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. METHODS: The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein-protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. RESULTS: We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p < 0.05), but there was no significant difference in histologic grade, histologic type, tumor size, lymph node metastasis, TMN stage, subtypes, or recurrence (p > 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20-6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06-3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression. CONCLUSIONS: These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

Intrinsic Properties of Macroscopically Tuned Gallium Nitride Single-Crystalline Facets for Electrocatalytic Hydrogen Evolution.

The anisotropy of crystalline materials results in different physical and chemical properties on different facets, which warrants an in-depth investigation. Macroscopically facet-tuned, high-purity gallium nitride (GaN) single crystals were synthesised and machined, and the electrocatalytic hydrogen evolution reaction (HER) was used as the model reaction to show the differences among the facets. DFT calculations revealed that the Ga and N sites of GaN (100) had a considerably smaller ΔGH* value than those of the metal Ga site of GaN (001) or N site of GaN (00-1), thereby indicating that GaN (100) should be more catalytically active for the HER on account of its nonpolar facet. Subsequent experiments testified that the electrocatalytic performance of GaN (100) was considerably more efficient than that of other facets for both acidic and alkaline HERs. Moreover, the GaN crystal with a preferentially (100) active facet had an excellently durable alkaline electrocatalytic HER for more than 10 days. This work provides fundamental insights into the exploration of the intrinsic properties of materials and designing advanced materials for physicochemical applications.

Liver tissue metabolic profiling and pathways of non-alcoholic steatohepatitis in rats.

AIM: The mechanisms of non-alcoholic steatohepatitis (NASH) in hepatocytes are unknown. Our aim is to study the tissue metabolic profiling and pathways of NASH. METHODS: We built rat models for simple steatosis and NASH and analyzed the liver extract using a liquid chromatograph-mass spectrometer. The acquired data were processed by multivariate principal component analysis and partial least squares discriminant analysis (PLS-DA) to obtain metabolic profiling. Orthogonal projections to latent structures DA was used to obtain metabolites capable of distinguishing NASH and steatosis. The total differences in the metabolites between groups were analyzed to determine their metabolic pathways. RESULTS: Principal component analysis showed that the metabolic profiles of NASH and steatosis are different. The PLS-DA modeling revealed a clear separation between two groups with parameters R2 Y and Q2 Y all greater than 0.7. The orthogonal projections to latent structures DA model identified 171 metabolites capable of distinguishing NASH from steatosis. The identified metabolites are involved in fatty acid metabolism, tryptophan metabolism, the urea cycle, and the citric acid cycle in hepatocytes. CONCLUSIONS: These metabolic profiles and pathways in rat hepatocytes will offer useful information when studying metabolic disorders in patients with NASH.

USP5 facilitates diabetic retinopathy development by stabilizing ROBO4 via deubiquitination.

Ubiquitin-specific proteases (USPs) have been proved to play important roles in the progression of diabetic retinopathy. In this study, we explored the role of USP5 and its possible mechanisms in diabetic retinopathy development. Cell proliferation, apoptosis, inflammation and oxidative stress were determined using CCK-8 assay, EdU staining assay, flow cytometry, and ELISA, respectively. The mRNA and protein expression of ROBO4 and USP5 were measured through RT-qPCR and western blot, respectively. Co-IP and deubiquitination assay were conducted to evaluate the interaction between ROBO4 and USP5. The results showed that high glucose (HG) stimulation significantly led to HRPE cell damage as described by suppressing proliferation, and promoting oxidative stress, inflammation and apoptosis. ROBO4 was markedly increased in diabetic retinopathy plasma samples and HG-triggered HRPE cells. Depletion of ROBO4 could alleviate HG-caused HRPE cell damage. USP5 was also significantly elevated in diabetic retinopathy plasma samples and HG-triggered HRPE cells. USP5 overexpression aggravated HG-induced HRPE cell damage. USP5 stabilized ROBO4 through deubiquitination. Moreover, USP5 knockdown decreased ROBO4 expression to mitigate HG-triggered cell damage in HRPE cells. USP5 stabilized ROBO4 via deubiquitination to repress cell proliferation, and facilitate inflammation, cell apoptosis and oxidative stress in HG-treated HRPE cells, thereby promoting the development of diabetic retinopathy.

Application of self-assembly palladium single-atom nanozyme over polyoxometalates in protection against neomycin-induced hearing loss by inhibiting ferroptosis.

Deafness mainly results from irreversible impairment of hair cells (HCs), which may relate to oxidative stress, yet therapeutical solutions is lacked due to limited understanding on the exact molecular mechanism. Herein, mimicking the molecular structure of natural enzymes, a palladium (Pd) single-atom nanozyme (SAN) was fabricated, exhibiting superoxide dismutase and catalase activity, transforming reactive oxygen species (ROS) into O2 and H2O. We examined the involvement of Pd in neomycin-induced HCs loss in vitro and in vivo over zebrafish. Our results revealed that neomycin treatment induced apoptosis in HCs, resulting in substantial of ROS elevation in HEI-OC1 cells, decrease in mitochondrial membrane potential, and increase in lipid peroxidation and iron accumulation, ultimately leading to iron-mediated cell death. Noteworthy, Pd SAN treatment exhibited significant protective effects against HCs damage and impaired HCs function in zebrafish by inhibiting ferroptosis. Furthermore, the application of iron death inducer RSL3 resulted in notable exacerbation of neomycin-induced harm, which was mitigated by Pd administration. Our investigation demonstrates that antioxidants is promising for inhibiting ferroptosis and repairing of mitochondrial function in HCs and the enzyme-mimic SAN provides a good strategy for designing drugs alleviating neomycin-induced ototoxicity.

Antioxidant activities of metal single-atom nanozymes in biomedicine.

Nanozymes are a class of nanomaterials with enzyme-like activity that can mimic the catalytic properties of natural enzymes. The small size, high catalytic activity, and strong stability of nanozymes compared to those of natural enzymes allow them to not only exist in a wide temperature and pH range but also maintain stability in complex environments. Recently developed single-atom nanozymes have metal active sites composed of a single metal atom fixed to a carrier. These metal atoms can act as independent catalytically active centers. Metal single-atom nanozymes have a homogeneous single-atom structure and a suitable coordination environment for stronger catalytic activity and specificity than traditional nanozymes. The antioxidant metal single-atom nanozymes with the ability of removing reactive oxygen species (ROS) can simulate superoxidase dismutase, catalase, and glutathione peroxidase to show different effects in vivo. Furthermore, due to the similar structure of antioxidant enzymes, a metal single-atom nanozyme often has multiple antioxidant activities, and this synergistic effect can more efficiently remove ROS related to oxidative stress. The versatility of single-atom nanozymes encompasses a broad spectrum of biomedical applications such as anti-oxidation, anti-infection, immunomodulatory, biosensing, bioimaging, and tumor therapy applications. Herein, the nervous, circulatory, digestive, motor, immune, and sensory systems are considered in order to demonstrate the role of metal single-atom nanozymes in biomedical antioxidants.

A simple nomogram for predicting the mortality of PICU patients with sepsis-associated encephalopathy: a multicenter retrospective study.

Background: As one of the serious complications of sepsis in children, sepsis-associated encephalopathy (SAE) is associated with significantly poor prognosis and increased mortality. However, predictors of outcomes for pediatric SAE patients have yet to be identified. The aim of this study was to develop nomograms to predict the 14-day and 90-day mortality of children with SAE, providing early warning to take effective measures to improve prognosis and reduce mortality. Methods: In this multicenter, retrospective study, we screened 291 patients with SAE admitted to the PICU between January 2017 and September 2022 in Shandong Province. A least absolute shrinkage and selector operation (LASSO) method was used to identify the optimal prognostic factors predicting the outcomes in pediatric patients with SAE. Then, multivariable logistic regression analysis was performed based on these variables, and two nomograms were built for visualization. We used the area under the curve (AUC), calibration curves and decision curves to test the accuracy and discrimination of the nomograms in predicting outcomes. Results: There were 129 patients with SAE in the training cohort, and there were 103 and 59 patients in the two independent validation cohorts, respectively. Vasopressor use, procalcitonin (PCT), lactate and pediatric critical illness score (PCIS) were independent predictive factors for 14-day mortality, and vasopressor use, PCT, lactate, PCIS and albumin were independent predictive factors for 90-day mortality. Based on the variables, we generated two nomograms for the early identification of 14-day mortality (AUC 0.853, 95% CI 0.787-0.919, sensitivity 72.4%, specificity 84.5%) and 90-day mortality (AUC 0.857, 95% CI 0.792-0.923, sensitivity 72.3%, specificity 90.6%), respectively. The calibration plots for nomograms showed excellent agreement of mortality probabilities between the observed and predicted values in both training and validation cohorts. Decision curve analyses (DCA) indicated that nomograms conferred high clinical net benefit. Conclusion: The nomograms in this study revealed optimal prognostic factors for the mortality of pediatric patients with SAE, and individualized quantitative risk evaluation by the models would be practical for treatment management.

Identification of GZMA as a Potential Therapeutic Target Involved in Immune Infiltration in Breast Cancer by Integrated Bioinformatical Analysis.

Purpose: Granzyme A (GZMA) is a potential prognostic target for various cancer types. However, its therapeutic significance in breast cancer with immune infiltration remains controversial. We analyzed GZMA expression and its prognostic value in breast cancer with immune cell infiltration. Patients and methods: Data was obtained from patients with breast cancer registered at The Cancer Genome Atlas. A correlation was performed between GZMA expression and patient's clinicopathological features such as age, pathologic stage, metastasis stage, overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI). Kaplan-Meier analyses and Cox proportional hazard regression model were used to examine the predictive significance of GZMA expression for breast cancer. The co-expression pattern of GZMA was assessed by the LinkedOmics web portal. The relationship between GZMA expression and immune cells was analyzed using the TIMER database. The correlation between GZMA and lymphocytes and immunomodulators was established with the TISIDB database. Results: There was a lower GZMA expression in breast cancer tissue than in normal tissue. Interestingly, GZMA expression was associated with age, pathologic stage, and the Tumour, Node, and Metastasis stage. Overexpression of GZMA was also associated with better OS, DSS, and PFI. Based on the Cox regression analysis, GZMA was identified as an independent favorable prognostic factor for breast cancer. Our findings demonstrated a strong association between GZMA and T-cell checkpoints (PD-1, PD-L1, and cytotoxic T lymphocyte-associated antigen (CTLA-4)) in breast cancer. Moreover, we evaluated the interactions between GZMA expression and markers of dendritic and CD8+ T cells using quantitative immunofluorescence. We discovered that increased infiltration of dendritic and CD8+ T cells was associated with GZMA expression in breast cancer. Conclusion: GZMA expression is associated with a favorable prognosis in breast cancer and is significantly correlated with immune cell infiltration. GZMA may be considered a promising therapeutic target for patients with breast cancer.

SIRT7 Downregulation Promotes Breast Cancer Metastasis Via LAP2α-Induced Chromosomal Instability.

Chromosomal instability (CIN) plays an important role in the initiation and progression of carcinomas. However, the regulatory mechanism of metastasis mediated by CIN in breast cancer is not fully understood. Here, we aimed to demonstrate that the deregulation of SIRT7 and lamina-associated polypeptide 2α (LAP2α) critically contributes to CIN-induced metastasis in breast cancer. Expression of SIRT7 and chromosome stability-related genes was examined using western blotting, quantitative real-time PCR, immunohistochemistry, and immunofluorescence; functional significance of SIRT7 was examined using in vitro and in vivo models; and interaction between SIRT7 and LAP2α was assessed by co-inmunoprecipitation (Co-IP) assays. Doxorubicin (DOX) inhibited SIRT7 expression and enhanced CIN in breast cancer cells; SIRT7 deficiency led to CIN in breast cancer cells. Co-IP approach and immunohistochemistry demonstrated that SIRT7 interacted directly and positively with LAP2α and SIRT7 knockdown led to increased ubiquitination-dependent degradation of LAP2α and reduced protein levels of LAP2α, whereas LAP2α knockdown did not affect SIRT7 expression. In vitro and in vivo evidence revealed that SIRT7 promotes breast cancer metastasis through the SIRT7/LAP2α axis. In summary, SIRT7 interacts with LAP2α to regulate CIN and metastasis in breast cancer, and inhibition of SIRT7/LAP2α axis represents a potential therapeutic strategy for preventing breast cancer metastasis.

Comprehensive Analysis of the Expression and Prognosis for Tripartite Motif-Containing Genes in Breast Cancer.

Tripartite motif-containing genes (TRIMs), with a ubiquitin ligase's function, play critical roles in antitumor immunity by activating tumor-specific immune responses and stimulating tumor proliferation, thus affecting patient outcomes. However, the expression pattern and prognostic values of TRIMs in breast cancer (BC) are not well clarified. In this study, several datasets and software were integrated to perform a comprehensive analysis of the expression pattern in TRIMs and investigate their prognosis values in BC. We found that TRIM59/46 were significantly upregulated and TRIM66/52-AS1/68/7/2/9/29 were decreased in BC and validated them using an independent cohort. The expression of numerous TRIMs are significantly correlated with BC molecular subtypes, but not with tumor stages or patient age at diagnosis. Higher expression of TRIM3/14/69/45 and lower expressions of TRIM68/2 were associated with better overall survival in BC using the Kaplan-Meier analysis. The multivariate Cox proportional hazards model identified TRIM45 as an independent prognostic marker. Further analysis of single-cell RNA-seq data revealed that most TRIMs are also expressed in nontumor cells. Higher expression of some TRIMs in the immune or stromal cells suggests an important role of TRIMs in the BC microenvironment. Functional enrichment of the co-expression genes indicates that they may be involved in muscle contraction and interferon-gamma signaling pathways. In brief, through the analysis, we provided several TRIMs that may contribute to the tumor progression and TRIM45 as a potential new prognostic biomarker for BC.

DNA Sequence-Dependent Binding of Linker Histone gH1 Regulates Nucleosome Conformations.

Sequence-dependent binding between DNA and proteins in chromatin is an essential part of gene expression. Linker histone H1 is an important protein in the regulation of chromatin compartmentalization and compaction, and its binding with the nucleosome is sensitive to the DNA sequence. Although the interactions of H1 and DNA have been widely investigated, the mechanism of nucleosome conformation changes induced by the DNA-sequence-dependent binding with gH1 (globular H1.0) remains largely unclear at the atomic level. In the present molecular dynamics simulations, both linker and dyad DNAs were mutated to investigate the conformational changes of the nucleosome induced by the sequence-dependent binding of gH1 based on the on-dyad binding mode. Our results indicate that gH1 is insensitive to the DNA sequence of the dyad DNA but presents an apparent preference to linker DNA with an AT-rich sequence. Moreover, this specific binding induces the entry/exit region of a nucleosome to a tight conformation and regulates the accessibility of core histones. Considering that the entry/exit region of the nucleosome is a crucial binding site for many functional proteins related to gene expression, the conformational change at this region could represent an important gene regulation signal.

ASPM Is a Prognostic Biomarker and Correlates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma and Liver Hepatocellular Carcinoma.

Background: Abnormal spindle microtubule assembly (ASPM) is a centrosomal protein and that is related to a poor clinical prognosis and recurrence. However, the relationship between ASPM expression, tumor immunity, and the prognosis of different cancers remains unclear. Methods: ASPM expression and its influence on tumor prognosis were analyzed using the Tumor Immune Estimation Resource (TIMER), UALCAN, OncoLnc, and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The relationship between ASPM expression and tumor immunity was analyzed using the TIMER and GEPIA databases, and the results were further verified using qPCR, western blot, and multiplex quantitative immuno fluorescence. Results: The results showed that ASPM expression was significantly higher in most cancer tissues than in corresponding normal tissues, including kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and breast invasive carcinoma (BRCA). ASPM expression was significantly higher in late-stage cancers than in early-stages cancers (e.g., KIRC, KIRP, LIHC, LUAD, and BRCA; p < 0.05), demonstrating a possible role of ASPM in cancer progression and invasion. Moreover, our data showed that high ASPM expression was associated with poor overall survival, and disease-specific survival in KIRC and LIHC (p < 0.05). Besides, Cox hazard regression analysis results showed that ASPM may be an independent prognostic factor for KIRC and LIHC. ASPM expression showed a strong correlation with tumor-infiltrating B cells, CD8+ T cells, and M2 macrophages in KIRC and LIHC. Conclusions: These findings demonstrate that the high expression of ASPM indicates poor prognosis as well as increased levels of immune cell infiltration in KIRC and LIHC. ASPM expression may serve as a novel prognostic biomarker for both the clinical outcome and immune cell infiltration in KIRC and LIHC.

Corrigendum: ASPM is a prognostic biomarker and correlates with immune infiltration in kidney renal clear cell carcinoma and liver hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.632042.].

TRIM58 inactivates p53/p21 to promote chemoresistance via ubiquitination of DDX3 in breast cancer.

Chemotherapy resistance is that the most important reason behind of carcinoma treatment failure but the underlying molecular mechanisms are unclear. Members of the tripartite motifcontaining protein (TRIM) family play crucial roles in the carcinogenesis and development of resistance against chemotherapy. Herein, we first confirmed that TRIM58 is highly expressed in triple-negative breast cancer tissues and drug-resistant MCF7/ADR cells. Furthermore, TRIM58 knockdown resulted in increased sensitivity of MCF7/ADR cells toward doxorubicin in vitro and in vivo. In contrast, TRIM58 overexpression in breast cancer cells increased doxorubicin resistance. TRIM58 was found to interact with DDX3, a protein recently reported to modulate resistance against chemotherapy. We found that TRIM58 negatively regulates DDX3 expression downstream of the P53/P21 pathway, and that DDX3 is degraded by TRIM58-mediated ubiquitination. Knockdown of DDX3 reversed doxorubicin chemotherapy sensitivity induced by TRIM58 knockdown via the P53/P21 pathway.Our study reveals that TRIM58 mediates a novel mechanism underlying the development of resistance against chemotherapy in breast cancer and provides potential targets for developing novel therapeutic targets for breast cancer.

Supplementation of graded levels of rumen-protected choline to a pelleted total mixed ration did not improve the growth and slaughter performance of fattening lambs.

Choline is an essential nutrient in ruminant diets, which contributes to the fundamental biological functions of the animal. However, choline is easily degraded in the rumen before it can be absorbed. Rumen-protected choline (RPC) supplementation might support the fast growth of ruminants. This study aimed to investigate the effects of supplementing graded levels of RPC in a pelleted total mixed ration for fattening lambs. Sixty three-month-old male Small Tail Han and northeast fine wool sheep hybrid lambs with a liveweight of 15.3 ± 1.8 kg (mean ± SD) were fed designated diets and randomly assigned into five treatment groups (n = 12 per group). The five treatments were the rate of RPC supplementation at 0, 1.25, 2.50, 3.75, and 5.00 g (equivalent to 0, 0.31, 0.63, 0.94, and 1.25 g of choline chloride, respectively)/kg basal diet and the RPC-supplemented feed was offered for 112 days after 12 days of adaptation. Average daily gain, dry matter intake, and nutrient digestibility were similar across treatments. The rumen pH was quadratically significant among treatments, with the lowest and highest pH observed from the 2.5 and 5 g/kg RPC supplement groups, respectively (P = 0.02). After feeding, the ruminal ammonia concentrations among treatments were different (P < 0.05), with the highest value observed from the 5 g/kg RPC supplement group. Microbial crude protein level was different, with the highest value recorded from the 0 g/kg RPC supplement group (P = 0.028). A linear effect (P < 0.05) was observed from short-chain fatty acid values among treatments before and after feeding. Serum albumin (P = 0.003) and albumin/globulin ratio (P = 0.002) had a quadratic effect, with the highest value found in the 0 g/kg RPC supplement group. Abdominal fat was higher in RPC-supplemented groups (P < 0.05) compared to the control group. Drip loss was 65% higher in RPC-supplemented groups compared to the control group (P = 0.012). Overall, the study results showed an effect of RPC on ruminal parameters, but the supplementation of low-level RPC did not improve the growth and slaughter performance of fattening lambs.