Evaluating the psychometric properties of the simplified Chinese version of PROMIS-29 version 2.1 in patients with hematologic malignancies.

The Patient-Reported Outcomes Measurement Information System 29-item Profile version 2.1 (PROMIS-29 V2.1) is a widely utilized self-reported instrument for assessing health outcomes from the patients' perspectives. This study aimed to evaluate the psychometric properties of the PROMIS-29 V2.1 Chinese version among patients with hematological malignancy. Conducted as a cross-sectional, this research was approved by the Medical Ethical Committee of the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (registration number QTJC2022002-EC-1). We employed convenience sampling to enroll eligible patients with hematological malignancy from four tertiary hospitals in Tianjin, Shandong, Jiangsu, and Anhui province in China between June and August 2023. Participants were asked to complete a socio-demographic information questionnaire, the PROMIS-29 V2.1, and the Functional Assessment of Cancer Therapy-General (FACT-G). We assessed the reliability, ceiling and floor effects, structural, convergent discriminant and criterion validity of the PROMIS-29 V2.1. A total of 354 patients with a mean age of 46.93 years was included in the final analysis. The reliability of the PROMIS-29 V2.1 was affirmed, with Cronbach's α for the domains ranging from 0.787 to 0.968. Except sleep disturbance, the other six domains had ceiling effects, which were seen on physical function (26.0%), anxiety (37.0%), depression (40.4%), fatigue (18.4%), social roles (18.9%) and pain interference (43.2%), respectively. Criterion validity was supported by significant correlations between the PROMIS-29 V2.1 and FACT-G scores, as determined by the Spearman correlation test (P < 0.001). Confirmatory factor analysis (CFA) indicated a good model fit, with indices of χ2/df (2.602), IFI (0.960), and RMSEA (0.067). The Average Variance Extracted (AVE) values for the seven dimensions of PROMIS-29 V2.1, ranging from 0.500 to 0.910, demonstrated satisfactory convergent validity. Discriminant validity was confirmed by ideal √AVE values. The Chinese version of the PROMIS-29 V2.1 profile has been validated as an effective instrument for assessing symptoms and functions in patients with hematological malignancy, underscoring its reliability and applicability in this specific patient group.

Mononuclear Iron Pyridinethiolate Complex Promoted CO2 Photoreduction via Rapid Intramolecular Electron Transfer.

Designing earth-abundant metal complexes as efficient molecular photocatalysts for visible light-driven CO2 reduction is a key challenge in artificial photosynthesis. Here, we demonstrated the first example of a mononuclear iron pyridine-thiolate complex that functions both as a photosensitizer and catalyst for CO2 reduction. This single-component bifunctional molecular photocatalyst efficiently reduced CO2 to formate and CO with a total turnover number (TON) of 46 and turnover frequency (TOF) of 11.5 h-1 in 4 h under visible light irradiation. Notably, the quantum yield was determined to be 8.4 % for the generation of formate and CO at 400 nm. Quenching experiments indicate that high photocatalytic activity is mainly attributed to the rapid intramolecular quenching protocol. The mechanism investigation by DFT calculation and electrochemical studies revealed that the protonation of Febpy(pyS)2 is indispensable step for photocatalytic CO2 reduction.

Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex.

BACKGROUND: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear. METHODS: Given the known role of Ptpn23 (protein tyrosine phosphatase, nonreceptor type 23) in regulating membrane deformation, its expression in patients with dilated cardiomyopathy was determined. Taking advantage of Cre/Loxp, CRISPR/Cas9, and adeno-associated virus 9 (AAV9)-mediated in vivo gene editing, we generated cardiomyocyte-specific Ptpn23 and Actn2 (α-actinin-2, a major component of Z-discs) knockout mice. We also perturbed the DGC by using dystrophin global knockout mice (DmdE4*). MM 4-64 and Di-8-ANEPPS staining, Cav3 immunofluorescence, and transmission electron microscopy were performed to determine T-tubule structure in isolated cells and intact hearts. In addition, the assembly of the DGC with Ptpn23 and dystrophin loss of function was determined by glycerol-gradient fractionation and SDS-PAGE analysis. RESULTS: The expression level of Ptpn23 was reduced in failing hearts from dilated cardiomyopathy patients and mice. Genetic deletion of Ptpn23 resulted in disorganized T-tubules with enlarged diameters and progressive dilated cardiomyopathy without affecting sarcomere organization. AAV9-mediated mosaic somatic mutagenesis further indicated a cell-autonomous role of Ptpn23 in regulating T-tubule formation. Genetic and biochemical analyses showed that Ptpn23 was essential for the integrity of costameres, which anchor the T-tubule membrane to Z-discs, through interactions with α-actinin and dystrophin. Deletion of α-actinin altered the subcellular localization of Ptpn23 and DGCs. In addition, genetic inactivation of dystrophin caused similar T-tubule defects to Ptpn23 loss-of-function without affecting Ptpn23 localization at Z-discs. Last, inducible Ptpn23 knockout at 1 month of age showed Ptpn23 is also required for the maintenance of T-tubules in adult cardiomyocytes. CONCLUSIONS: Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.

Molecular Engineering of Copper Phthalocyanine for CO2 Electroreduction to Methane.

Efficient electrochemical CO2 reduction reaction (ECO2RR) to multi-electron reductive products remains a great challenge. Herein, molecular engineering of copper phthalocyanines (CuPc) was explored by modifying electron-withdrawing groups (EWGs) (cyano, sulfonate anion) and electron-donating groups (EDGs) (methoxy, amino) to CuPc, then supporting onto carbon paper or carbon cloth by means of droplet coating, loading with carbon nanotubes and coating in polypyrrole (PPy). The results showed that the PPy-coated CuPc effectively catalysed ECO2RR to CH4. Interestingly, experimental results and DFT calculations indicated EWGs markedly improved the selectivity of methane for the reason that the introduction of EWGs reduces electron density of catalytic active center, resulting in a positive move to initial reduction potential. Otherwise, the modification of EDGs significantly reduces the selectivity towards methane. This electronic effect and heterogenization of CuPc are facile and effective molecular engineering, benefitting the preparation of electrocatalysts for further reduction of CO2.

Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.

AIM: The study aimed to use network pharmacology research and in vitro experiments to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary thyroid carcinoma. BACKGROUND: Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis are the leading causes of death in patients with PTC. A key research focus in thyroid cancer treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including cancer, but no study has been undertaken to determine whether it can help prevent PTC. OBJECTIVE: In this study, we attempted to determine through network pharmacology and in vitro experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle and invasive migration. METHODS: To predict the probable targets and underlying mechanisms of silybin against PTC, a network pharmacology research was performed. In vitro experiments were conducted to further evaluate silybin's anti-cancer properties and priority targets against PTC. RESULTS: The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment analysis suggested that the target genes were enriched in functions and pathways related to PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks, the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1), N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint gene expression levels were positively correlated with the expression levels of the hub genes. Silybin decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations. When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked, CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were dramatically reduced, while E-cadherin expression was significantly elevated. CONCLUSION: These findings provide preliminary evidence that silybin inhibits PTC cell proliferation, metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological checkpoint gene expression levels. These studies provide a theoretical and experimental scientific basis for the potential anticancer effects of silybin on PTC.

Comparison of temporary external and percutaneous k-wire fixations for treatment of ankle fracture-dislocations.

PURPOSE: Ankle fracture-dislocations are among the most severe injuries, and the use of an external fixator as a recommended fixation method has some disadvantages. The aim of this study was to compare the clinical outcomes and complication rates of external and K-wire fixations in the treatment of ankle fracture dislocations. METHODS: A total of 67 patients with ankle fracture-dislocations requiring temporary external or percutaneous K-wire fixation were included. The exclusion criteria were pilon fractures, open fractures, and those who required acute open reduction internal fixation (ORIF). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, a 10-point visual analog scale (VAS) score (range 0-10), and complications before and after the definitive surgery were recorded. RESULTS: A significant difference between the two groups was not observed for age, sex, affected side, fracture type, smoking status, or diabetes. The average AOFAS scores were 83.2 and 83.3, the median VAS scores were 3 and 3, and the complication rates were 32.4% and 6.7% in the external and K-wire fixation groups, respectively (p = 0.010). However, skin necrosis, re-dislocation of the ankle, surgical wound infection, and posttraumatic ankle osteoarthritis frequency were not significantly different between the groups, except for pin-sites infection (p = 0.036). CONCLUSION: Ankle fracture-dislocations using percutaneous k-wire fixation showed a low rate of complications and favorable clinical outcomes. This method could be a good alternative treatment option for ankle fracture-dislocations.

Nogo-B mediates endothelial oxidative stress and inflammation to promote coronary atherosclerosis in pressure-overloaded mouse hearts.

AIMS: Endothelial dysfunction plays a pivotal role in atherosclerosis, but the detailed mechanism remains incomplete understood. Nogo-B is an endoplasmic reticulum (ER)-localized protein mediating ER-mitochondrial morphology. We previously showed endothelial Nogo-B as a key regulator of endothelial function in the setting of hypertension. Here, we aim to further assess the role of Nogo-B in coronary atherosclerosis in ApoE-/- mice with pressure overload. METHODS AND RESULTS: We generated double knockout (DKO) mouse models of systemically or endothelium-specifically excising Nogo-A/B gene on an ApoE-/- background. After 7 weeks of transverse aortic constriction (TAC) surgery, compared to ApoE-/- mice DKO mice were resistant to the development of coronary atherosclerotic lesions and plaque rapture. Sustained elevation of Nogo-B and adhesion molecules (VCAM-1/ICAM-1), early markers of atherosclerosis, was identified in heart tissues and endothelial cells (ECs) isolated from TAC ApoE-/- mice, changes that were significantly repressed by Nogo-B deficiency. In cultured human umbilical vein endothelial cells (HUVECs) exposure to inflammatory cytokines (TNF-α, IL-1ß), Nogo-B was upregulated and activated reactive oxide species (ROS)-p38-p65 signaling axis. Mitofusin 2 (Mfn2) is a key protein tethering ER to mitochondria in ECs, and we showed that Nogo-B expression positively correlated with Mfn2 protein level. And Nogo-B deletion in ECs or in ApoE-/- mice reduced Mfn2 protein content and increased ER-mitochondria distance, reduced ER-mitochondrial Ca2+ transport and mitochondrial ROS generation, and prevented VCAM-1/ICAM-1 upregulation and EC dysfunction, eventually restrained atherosclerotic lesions development. CONCLUSION: Our study revealed that Nogo-B is a critical modulator in promoting endothelial dysfunction and consequent pathogenesis of coronary atherosclerosis in pressure overloaded hearts of ApoE-/- mice. Nogo-B may hold the promise to be a common therapeutic target in the setting of hypertension.

Identification of prognostic biomarkers of breast cancer based on the immune-related gene module.

Breast cancer (BC) is highly malignant and its mortality rate remains high. The development of immunotherapy has gradually improved the prognosis and survival rate of patients. Therefore, identifying molecular markers concerned with BC immunity is of great importance for the treatment of this disease. The Cancer Genome Atlas-breast invasive carcinoma (TCGA-BRCA) was utilized as the training set while the BC expression dataset from the gene expression omnibus database was taken as the validation set here. Weighted gene co-expression network analysis combined with Pearson analysis and Tumor immune estimation resource (TIMER) was used to obtain immune cell-related hub gene module. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on this module. Then, receiver operating characteristic curves combining Kaplan-Meier was used to evaluate the effectiveness of the model. Feature genes were screened and the independence of risk score was evaluated by univariate and multivariate Cox analyses. Differences in immune characteristics were analyzed via single-sample gene set enrichment analysis and CIBERSORT, and differences in gene mutation frequency were assessed via GenVisR analysis. Finally, the expression levels of prognostic feature genes in BC cells were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In this study, cell immune-related gene modules in TCGA-BRCA were successfully excavated, and a five-gene (TNFRSF14, NFKBIA, DLG3, IRF2, and CYP27A1) prognostic model was established. The prognostic model could effectively forecast the prognosis and survival rate of BC patients. The result showed that human leukocyte antigen-related proteins and macrophage M2 scores were remarkably highly expressed in the high-risk group, whereas CD8+ T cells, natural killer cells, M1, and other anti-tumor cells were lowly expressed. The model could be used as an independent prognostic factor to predict the prognosis of BC patients. The results of qRT-PCR validation were consistent with the results in the database, that is, except DLG3, the other four feature genes were lowly expressed in BC. The five-gene model established in this study can predict the prognostic and immune mode of BC patients effectively, which is anticipated to become a feasible molecular target for BC therapy.

Extracellular ATP-induced calcium oscillations regulating the differentiation of osteoblasts through aerobic oxidation metabolism pathways.

INTRODUCTION: The increase of ATP concentration in the extracellular space represents one of the effective signals that stimulate the physiological activities of cells when the bone is exposed to external mechanical stimulation such as stretching and shear stress force throughout life. However, the effects of ATP on osteoblast differentiation and related mechanisms are not well understood. MATERIALS AND METHODS: In this study, the roles of extracellular ATP on osteoblast differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. RESULTS: Our results showed that 100 µM extracellular ATP initiated intracellular calcium ([Ca2+]i) oscillations via the calcium-sensing receptor (P2R) and promoted the differentiation of MC3T3-E1 cells. Metabolomics analysis showed that the differentiation of MC3T3-E1 cells depended on aerobic oxidation, but little glycolysis. Moreover, the differentiation of MC3T3-E1 cells and aerobic oxidation were suppressed with the inhibition of AMP-activated protein kinase (AMPK). CONCLUSION: These results indicate that calcium oscillations triggered by extracellular ATP can activate aerobic oxidation through AMPK-related signaling pathways and thus promote osteoblast differentiation.

Extracellular Calcium-Induced Calcium Transient Regulating the Proliferation of Osteoblasts through Glycolysis Metabolism Pathways.

During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca2+]i transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.

Long-term survivors demonstrate superior quality of life after haploidentical stem cell transplantation to matched sibling donor transplantation.

BACKGROUND: It has been well-documented that haplo-identical hematopoietic stem cell transplantation (HID-HSCT) can provide outcomes comparable to conventional matched sibling donor (MSD) HSCT, however, little is known about the effects on quality of life (QoL) in long-term survivors. This study is to investigate the differences in longitudinal performance of QoL between HID and MSD HSCT using a comprehensive assessment system. METHODS: This prospective study enrolled consecutive patients who had received allogenic-HSCT (allo-HSCT) between January 2018 and December 2019 in our center. All patients were informed to complete QoL questionnaires including the Mos 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, version 4), using an online applet, before transplantation and at scheduled time points after transplantation. The linear mixed-effects model was used to analyze the variation trend of different dimensions of both SF-36 and FACT-BMT with different follow-up times. RESULTS: Of the 425 participants, recipients of HID and MSD who survived more than 1 year (n = 230) were included in the final analysis of QoL (median age [range]: 36, [15, 66]). The 3 year overall survival (OS) of HID and MSD was 82.42% and 86.46%, respectively. QoL was assessed using both SF-36 and FACT-BMT and there was longitudinal recovery with clinical significance in the cohort. Compared to MSD-HSCT patients, HID-HSCT recipients demonstrated superior QoL performance in some subscales describing physical and mental wellness. Specifically, the difference in physical performance is more remarkable using FACT-BMT whereas that in mental wellness is more significant using SF36. In the subsequent stratified analysis, patients with a history of aGVHD or CMV reactivation demonstrated inferior QoL. CONCLUSIONS: Long-term survivors of HID HSCT achieved better QoL in some sub-scales compared to MSD HSCT. In addition, SF-36 and FACT-BMT demonstrated different performance thus combination of both improved capacity of the evaluation system.

To Explore the Inhibitory Mechanism of Quercetin in Thyroid Papillary Carcinoma through Network Pharmacology and Experiments.

Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein-protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.

Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy.

Glucose metabolism-related genes play an important role in the development and immunotherapy of many tumours, but their role in thyroid cancer is ambiguous. To investigate the role of glucose metabolism-related genes in the development of papillary thyroid cancer (PTC) and their correlation with the clinical outcome of PTC, we collected transcriptomic data from 501 PTC patients in the Cancer Genome Atlas (TCGA). We performed nonnegative matrix decomposition clustering of 2752 glucose metabolism-related genes from transcriptome data and classified PTC patients into three subgroups (C1 for high activation of glucose metabolism, C2 for low activation of glucose metabolism and C3 for moderate activation of glucose metabolism) based on the activation of different glucose metabolism-related genes in 10 glucose metabolism-related pathways. We found a positive correlation between the activation level of glucose metabolism and the tumour mutation burden (TMB), neoantigen number, mRNA stemness index (mRNAsi), age, and tumour stage in PTC patients. Next, we constructed a prognostic prediction model for PTC using six glucose metabolism-related genes (PGBD5, TPO, IGFBPL1, TMEM171, SOD3, TDRD9) and constructed a nomogram based on the risk score and clinical parameters of PTC patients. Both the prognostic risk prediction model and nomogram had high stability and accuracy for predicting the progression-free interval (PFI) in PTC patients. Patients were then divided into high-risk and low-risk groups by risk score. The high-risk group was sensitive to paclitaxel and anti-PD-1 treatment, and the low-risk group was sensitive to sorafenib treatment. We found that the high-risk group was enriched in inflammatory response pathways and associated with high level of immune cell infiltration. To verify the accuracy of the prognostic prediction model, we knocked down PGBD5 in PTC cells and found that the proliferation ability of PTC cells was significantly reduced. This suggests that PGBD5 may be a relatively important oncogene in PTC. Our study constructed a prognostic prediction model and classification of PTC by glucose metabolism-related genes, which provides a new perspective on the role of glucose metabolism in the development and immune microenvironment of PTC and in guiding chemotherapy, targeted therapy and immune checkpoint blockade therapy of PTC.

Thyroidectomy using a single-port cervico-mental angle approach.

Background: Over the last two decades, several endoscopic thyroidectomy methods have been developed. However, there are some limitations in these procedures. To date, the optimal surgical approach for thyroid cancer has not yet been developed. This study reported the surgical operation steps, clinical outcomes, and experience of 30 patients who underwent trans-cervico-mental angle single-port endoscopic thyroidectomy (TCMASPET) at our centre. Patients and Methods: A total of 30 patients were enrolled in the present study. Patients underwent unilateral or bilateral thyroidectomy through a cervico-mental angle incision of 2.48 ± 0.31 cm, after which the lymphoid adipose tissues in the central region were dissected. Results: All surgeries were successfully completed. Two patients underwent bilateral thyroid carcinoma resection with bilateral central region lymph node dissection, 23 patients received unilateral thyroid cancer resection with unilateral central region lymph node dissection, four patients underwent unilateral thyroid resection, and one patient received bilateral thyroid resection with unilateral central region lymph node dissection. No permanent post-operative complications were observed. Conclusions: TCMASPET was a safe and feasible approach that was relatively easy to perform. This approach may expand the indications for endoscopic thyroidectomy while maintaining excellent cosmetic outcomes.

Cobalt Phthalocyanine Cross-Linked Polypyrrole for Efficient Electroreduction of Low Concentration CO2 To CO.

Immobilizing cobalt phthalocyanine (CoPc) onto the electrode surface is a significant approach to performing efficient electrochemical CO2 reduction reaction (ECO2 RR). Herein, sulfylphenoxy decorated CoPc cross-linked polypyrrole is prepared by in situ polymerization on the surface of carbon cloth. The synthesized N-rich catalyst exhibits above 95 % Faradaic efficiency toward CO (FECO ) at -0.9 V versus reversible hydrogen electrode (RHE) at least for 10 h in aqueous solution and even enables direct electrolysis at low CO2 concentrations, being potential for coupling ECO2 RR with CO2 capture. This facile in situ polymerization strategy would pave the way for developing efficient and practical electrocatalysis for ECO2 RR.

Comprehensive analysis of PPPCs family reveals the clinical significance of PPP1CA and PPP4C in breast cancer.

The phosphoprotein phosphatase catalytic subunit (PPPCs) family has been shown to play an important role in the development and progression of various malignancies, but its expression patterns and biological functions in breast cancer (BC) remain unclear. Therefore, we aimed to investigate the clinical significance and biological functions of the PPPCs family to understand its possible significance in the diagnosis, prognosis and treatment of breast cancer. We comprehensively investigated the expression levels, diagnostic accuracy, prognostic outcomes, biological functions and effects on immune cell infiltration of the PPPCs family in breast cancer using online databases. Except for PPP1CB, PPP1CC, PPP5C and PPEF1, the mRNA expression levels of the PPPCs family in breast cancer tissues were significantly different from those in paracancerous tissues. The differentially expressed genes (DEGs) were associated with the clinicopathological parameters and prognosis of breast cancer. The DEGs were mainly associated with the WNT signaling pathway, antigen presentation and DNA repair. In addition, the DEGs significantly affected the infiltration of immune cells in breast cancer tissues. Among the PPPCs family, PPP1CA and PPP4C played a prominent role in the progression of breast cancer, and inhibition of PPP1CA and PPP4C expression by siRNA can significantly inhibit breast cancer cells proliferation and migration. In conclusion, the PPPCs family, especially PPP1CA and PPP4C, could be used as new biomarkers to improve diagnostic accuracy, predict prognosis and novel targets for the treatment of breast cancer.

Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

Modified sinus tarsi approach with a variable-angle locking anterolateral plate for Sanders type II and III calcaneal fractures.

BACKGROUND: We compared the effectiveness of the extensile lateral approach (ELA) and modified sinus tarsi approach (MSTA) with a variable-angle locking anterolateral plate in treating Sanders type II and III calcaneal fractures. METHODS: We reviewed 45 DIACFs treated by a single surgeon from 2017 to 2020. Open reduction using ELA and MSTA was performed in 25 and 20 patients, respectively. Follow-up evaluations included radiological assessments and clinical evaluations. RESULTS: Pre- and postoperative radiologic parameters for the calcaneus were significantly different. The average American Orthopaedic Foot and Ankle Society scores were 81.24 and 85.00, the mean visual analogue scale scores were 2.28 and 1.65, and the wound-related complication rates were 64.0% and 15.0% in the ELA and MSTA groups, respectively. Bony union was achieved in all cases. CONCLUSIONS: For Sanders type II and III fractures, MSTA seems to be a safer and more satisfactory method, with fewer postoperative complications.

Genome-wide identification of m6A-associated functional SNPs as potential functional variants for thyroid cancer.

m6A methylation has been demonstrated to be one of the most important epigenetic regulation mechanisms in cell differentiation and cancer development especially m6A derived diagnostic and prognostic biomarkers have been identified in the past several years. However, systemic investigation to the interaction between germline single-nucleotide polymorphisms (SNPs) and m6A has not been conducted yet. In this study, we collected previous identified significant thyroid cancer associated SNPs from UKB cohort (358 cases and 407,399 controls) and ICR cohort (3,001 patients and 287,550 controls) and thyroid eQTL (sample size = 574 from GTEx project) and m6A-SNP (N = 1,678,126) were applied to prioritize the candidate SNPs. Finally, five candidate genes (PLEKHA8, SMUG1, CDC123, RMI2, ACSM5) were identified to be thyroid cancer associated m6A-related genetic susceptibility. Loss and gain function studies of m6A writer proteins confirm that ACSM5 is regulated by m6A methylation of mRNA. Moreover, ACSM5 is downregulated in thyroid cancer and inversely correlated with PTC malignancy and patient survival. Together, our study highlight mRNA-seq and m6A-seq double analysis provided a novel approach to identify cancer biomarkers and understanding the heterogeneity of human cancers.

Real-time monitoring of aristolochic acid I reduction process using surface-enhanced Raman Spectroscopy with DFT simulation.

With the increasing number of reports on aristolochic acid I (AAI), more and more toxic and side effects have been discovered successively. The main recognized carcinogenic mechanism is that AAI is metabolized into aristololactam I (AAT) in the body by nitroreductases, ultimately forming AAT-DNA adducts that cause disease. However, the carcinogenic mechanism is still not well understood by currently reported indirect method, there has always been a great demand to develop a direct method for real-time monitoring such process. In this work, surface-enhanced Raman spectroscopy (SERS) was used for the first time to monitor the process of AAI under the action of reducing agent sodium borohydride and catalyst Raney nickel to form AAT. We first found the abundant intermediate product-amino derivative of AAI, which was never reported before by other methods. The AAT was then obtained by a one-step dehydration reaction from the amino derivative of AAI under such reduction conditions. The product of amino derivative of AAI and AAT were further verified by thin-layer chromatography, H nuclear magnetic resonance spectra, mass spectrometry, and ultra-high performance liquid chromatography. Furthermore, a density functional theory-supported in-depth vibrational characterization of AAI and AAT was performed. The monitoring of the AAI reduction process by SERS can be of great significance for further exploration of its pathogenic mechanism, prevention, and monitoring of "nephropathy" and other diseases caused by AAI.