A Novel Cartesian Plot Analysis for Fixed Monolayers That Relates Cell Phenotype to Transfer of Contents between Fibroblasts and Cancer Cells by Cell-Projection Pumping.

We recently described cell-projection pumping as a mechanism transferring cytoplasm between cells. The uptake of fibroblast cytoplasm by co-cultured SAOS-2 osteosarcoma cells changes SAOS-2 morphology and increases cell migration and proliferation, as seen by single-cell tracking and in FACS separated SAOS-2 from co-cultures. Morphological changes in SAOS-2 seen by single cell tracking are consistent with previous observations in fixed monolayers of SAOS-2 co-cultures. Notably, earlier studies with fixed co-cultures were limited by the absence of a quantitative method for identifying sub-populations of co-cultured cells, or for quantitating transfer relative to control populations of SAOS-2 or fibroblasts cultured alone. We now overcome that limitation by a novel Cartesian plot analysis that identifies individual co-cultured cells as belonging to one of five distinct cell populations, and also gives numerical measure of similarity to control cell populations. We verified the utility of the method by first confirming the previously established relationship between SAOS-2 morphology and uptake of fibroblast contents, and also demonstrated similar effects in other cancer cell lines including from melanomas, and cancers of the ovary and colon. The method was extended to examine global DNA methylation, and while there was no clear effect on SAOS-2 DNA methylation, co-cultured fibroblasts had greatly reduced DNA methylation, similar to cancer associated fibroblasts.

miR-449a Suppresses Tamoxifen Resistance in Human Breast Cancer Cells by Targeting ADAM22.

BACKGROUND/AIMS: Most of estrogen receptor positive breast cancer patients respond well initially to endocrine therapies, but often develop resistance during treatment with selective estrogen receptor modulators (SERMs) such as tamoxifen. Altered expression and functions of microRNAs (miRNAs) have been reportedly associated with tamoxifen resistance. Thus, it is necessary to further elucidate the function and mechanism of miRNAs in tamoxifen resistance. METHODS: Tamoxifen sensitivity was validated by using Cell Counting Kit-8 in tamoxifen-sensitive breast cancer cells (MCF-7, T47D) and tamoxifen-resistant cells (MCF-7/TAM, T47D/ TAM). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression level of miR-449a in tamoxifen-sensitive/-resistant cells and patient serums. Dual-luciferase assay was used to identify the binding of miR-449a and predicted gene ADAM22. The expression level of ADAM22 was determined by qRT-PCR and western blotting in miR-449a +/- breast cancer cells. Subsequently, rescue experiments were carried out to identify the function of ADAM22 in miR-449a-reduced tamoxifen resistance. Finally, Gene ontology (GO) and Protein-protein interaction analyses were performed to evaluate the potential mechanisms of ADAM22 in regulating tamoxifen resistance. RESULTS: MiR-449a levels were downregulated significantly in tamoxifen-resistant breast cancer cells when compared with their parental cells, as well as in clinical breast cancer serum samples. Overexpression of miR-449a re-sensitized the tamoxifen-resistant breast cancer cells, while inhibition of miR-449a conferred tamoxifen resistance in parental cells. Luciferase assay identified ADAM22 as a direct target gene of miR-449a. Additionally, silencing of ADAM22 could reverse tamoxifen resistance induced by miR-449a inhibition in ER-positive breast cancer cells. GO analysis results showed ADAM22 was mainly enriched in the biological processes of cell adhesion, cell differentiation, gliogenesis and so on. Protein-protein interaction analyses appeared that ADAM22 might regulate tamoxifen resistance through PPARG, LGI1, KRAS and LYN. CONCLUSION: Decreased miR-449a causes the upregulation of ADAM22, which induces tamoxifen resistance of breast cancer cells. These results suggest that miR-449a, functioning by targeting ADAM22, contributes to the mechanisms underlying breast cancer endocrine resistance, which may provide a potential therapeutic strategy in ER-positive breast cancers.

Aberrant Maspin mRNA Expression is Associated with Clinical Outcome in Patients with Pulmonary Adenocarcinoma.

BACKGROUND: The aim of this study was to investigate the expression level of maspin mRNA in pulmonary adenocarcinoma and to clarify its clinical significance in prediction of prognosis. MATERIAL/METHODS: RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks of 30 pairs of pulmonary adenocarcinoma (AC) tissues and adjacent noncancerous tissues (ANT) and in another 81 AC tissues. Expression of maspin mRNA was tested by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and the potential relationship between maspin mRNA expression and clinic pathological features of AC patients was analyzed. RESULTS: The expression of maspin mRNA was upregulated in AC samples compared with the ANT (p<0.001). Patients at advanced clinical stage (III) and patients with lymphatic metastasis showed higher maspin mRNA expression level than those in early-stage patients (I and II) (p=0.038) or with non-lymphatic metastasis (p=0.034). The Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in high maspin mRNA expression AC patients (p=0.007). Furthermore, multivariate analysis revealed that the expression of maspin mRNA was an independent prognostic marker for AC (p=0.040). CONCLUSIONS: Our study reveals that maspin mRNA was significantly up-regulated in tissues of AC patients. Maspin mRNA may be useful as a new marker of prognosis in AC.

Effects of paclitaxel liposome and capecitabine in the treatment of advanced gastric cancer by clinical observation.

OBJECTIVE: To evaluate the clinical effectiveness and side effects of paclitaxel liposome and capecitabine in the treatment of 34 cases with advanced gastric cancer. METHOD: For 64 patients with advanced gastric cancer, 30 cases were treated with docetaxel, cisplatin, and 5-fluorouracil (DCF group, control group), and 34 cases were treated with paclitaxel liposome and capecitabine (PC group, experimental group). DCF group: 75 mg/m2 of docetaxel, d1; 20 mg/m2 of cisplatin, d1-5; 350 mg/m2 of 5-fluorouracil, 4 - 6 hours of intravenous drip, d1-5, a cycle of 21 days. PC group: 135 mg/m2 of paclitaxel liposome, d1; 2,000 mg/m2.d of capecitabine, oral dose of twice per day, d1-14, a cycle of 21 days. CONTROL GROUP: the chemotherapy with a total of 122 cycles, with an average of 4.07 cycles; 2 cases of complete remission (CR), 12 cases of partial remission (PR), 7 cases of stable disease (SD), and 9 cases of development of progressive disease (PD); 46.7% of the immediate efficacy (remission rate (RR)), 70% of the disease control rate (DCR), 6.9 months of median PFS, and 12.5 months of median OS. Experimental group: the chemotherapy with a total of 169 cycles, with an average of 4.97 cycles; 14 cases of PR, 9 cases of SD, and 11 cases of PD; 46.7% of the immediate efficacy (RR), 70% of the disease control rate (DCR), 6.9 months of median progression-free survival (PFS), and 12.5 months of median overall survival (OS). There were no remarkable differences in RR, DCR, PFS curve, or OS curve for the two groups. The major toxicity of the two groups was hematological toxicity. The incidence of grade III - IV leucopenia in the control and experimental group was 56.7% and 17.6%, respectively. And the incidence of grade III - IV anemia was 13.3% and 2.9%, respectively. CONCLUSION: As an ideal schema in first-line therapy for advanced gastric cancer, paclitaxel liposome combined with capecitabine is generally well tolerated in clinical use, and is worth further extension.

In situ generated iron oxide nanosheet on iron foam electrode for enhanced electro-Fenton performance toward pharmaceutical wastewater treatment.

Electro-Fenton (EF) is considered to be an effective technology for the purification of organic wastewater containing antibiotics, but the construction of accessible and efficient heterogeneous EF catalytic materials still faces challenges. In this study, an iron foam-derived electrode (FeOx/if-400) was prepared by a simple method (chemical oxidation combined heat treatment). The fabricated electrode presented great EF degradation efficiency under wide pH range (almost completely removing 50 mg L-1 TNZ within 60 min) and maintained great stability after consecutive operation (>95% removal after six cycles). Also, the FeOx/if-400 electrode showed good purification ability for pharmaceutical wastewater as evaluated by the quadrupole time-of-flight mass spectrometry and the three-dimensional excitation-emission matrix fluorescence spectroscopy. Based on experimental results, characterization analysis, and density functional theory (DFT) calculations, the EF reaction mechanism of FeOx/if-400 electrode and the organics degradation pathways in simulated and real matrices were proposed. Significantly, the biotoxicity assessment of the degradation intermediate products was revealed by ECOSAR software and relative inhibition of E. coli, which fully proved the environmental friendliness of the EF process by the FeOx/if-400 cathode. This work provides a green and effective EF system, showing a promising application potential in the field of organic wastewater treatment containing antibiotic contaminants.

The Diagnostic Accuracy Between Radiomics Model and Non-radiomics Model for Preoperative of Microvascular Invasion of Solitary Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: Microvascular invasion (MVI) is a key prognostic factor for hepatocellular carcinoma (HCC). The predictive models for solitary HCC could potentially integrate more comprehensive tumor information. Owing to the diverse findings across studies, we aimed to compare radiomic and non-radiomic methods for preoperative MVI detection in solitary HCC. MATERIALS AND METHODS: Articles were reviewed from databases including PubMed, Embase, Web of Science, and the Cochrane Library until April 7, 2023. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model within a 95% confidence interval (CI). Diagnostic accuracy was assessed using summary receiver-operating characteristic curves and the area under the curve (AUC). Meta-regression and Z-tests identified heterogeneity and compared the predictive accuracy. Subgroup analyses were performed to compare the AUC of two methods according to study type, study design, tumor size, modeling methods, and imaging modality. RESULTS: The analysis incorporated 26 studies involving 3539 patients with solitary HCC. The radiomics models showed a pooled sensitivity and specificity of 0.79 (95%CI: 0.72-0.85) and 0.78 (95%CI: 0.73-0.82), with an AUC at 0.85 (95%CI: 0.82-0.88). Conversely, the non-radiomics models had sensitivity and specificity of 0.74 (95%CI: 0.65-0.81) and 0.88 (95%CI: 0.82-0.92) and an AUC of 0.88 (95%CI: 0.85-0.91). Subgroups with preoperative MRI, larger tumors, and functional imaging had higher accuracy than those using preoperative CT, smaller tumors, and conventional imaging. CONCLUSION: Non-radiomic methods outperformed radiomic methods, but high heterogeneity calls across studies for cautious interpretation.

Preoperative prediction power of radiomics and non-radiomics methods based on MRI for early recurrence in hepatocellular carcinoma: a systemic review and meta-analysis.

OBJECTIVE: To compare radiomics and non-radiomics in predicting early recurrence (ER) in patients with hepatocellular carcinoma (HCC) after curative surgery. METHODS: We systematically searched PubMed and Embase databases. Studies with clear reference criteria were selected. Data were extracted and assessed for quality using the quality in prognosis studies tool (QUIPS) by two independent authors. All included radiomics studies underwent radiomics quality score (RQS) assessment. We calculated sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) using random or fixed models with a 95%CI. Forest maps visualized the data, and summary receiver operating characteristic (sROC) curves with the area under the curve (AUC) were generated. Meta-regression and subgroup analyses explored sources of heterogeneity. We compared sensitivity, specificity, PLR, and NLR using the z-test and compared AUC values using the Delong test. RESULTS: Our meta-analysis included 10 studies comprising 1857 patients. For radiomics, the pooled sensitivity, specificity, AUC of sROC, PLR and NLR were 0.84(95%CI: 0.78-0.89), 0.80(95%CI: 0.75-0.85), 0.89(95%CI: 0.86-0.91), 4.28(95%CI: 3.48-5.27) and 0.20(95%CI: 0.14-0.27), respectively, but with significant heterogeneity (I2 = 60.78% for sensitivity, I2 = 55.79% for specificity) and potential publication bias (P = 0.04). The pooled sensitivity, specificity, AUC of sROC, PLR, NLR for non-radiomics were 0.75(95%CI:0.68-0.81), 0.78(95%CI:0.72-0.83), 0.83(95%CI: 0.80-0.86), 3.45(95%CI: 2.68-4.44) and 0.32(95%CI: 0.24-0.41), respectively. There was no significant heterogeneity in this group (I2 = 0% for sensitivity, I2 = 17.27% for specificity). Radiomics showed higher diagnostic accuracy (AUC: 0.89 vs. 0.83, P = 0.0456), higher sensitivity (0.84 vs. 0.75, P = 0.0385) and lower NLR (0.20 vs. 0.32, P = 0.0287). CONCLUSION: The radiomics from preoperative MRI effectively predicts ER of HCC and has higher diagnostic accuracy than non-radiomics. Due to potential publication bias and suboptimal RQS scores in radiomics, these results should be interpreted cautiously.

p75NTR antibody-conjugated microspheres: an approach to guided tissue regeneration by selective recruitment of endogenous periodontal ligament cells.

Repairing defects in alveolar bone is essential for regenerating periodontal tissue, but it is a formidable challenge. One promising therapeutic approach involves using a strategy that specifically recruits periodontal ligament cells (PDLCs) with high regenerative potential to achieve in situ regeneration of alveolar bone. In this study, we have created a new type of microsphere conjugated with an antibody to target p75 neurotrophin receptor (p75NTR), which is made of nano-hydroxyapatite (nHA) and chitosan (CS). The goal of this design is to attract p75NTR+hPDLCs selectively and promote osteogenesis. In vitro experiments demonstrated that the antibody-conjugated microspheres attracted significantly more PDLCs compared to non-conjugated microspheres. Incorporating nHA not only enhances cell adhesion and proliferation on the surface of the microsphere but also augments its osteoinductive properties. Microspheres effectively recruited p75NTR+ cells at bone defect sites in SD rats, as observed through immunofluorescent staining of p75NTR antibodies. This p75NTR antibody-conjugated nHA/CS microsphere presents a promising approach for selectively recruiting cells and repairing bone defects.

MOF-derived LDH modified flame-retardant polyurethane sponge for high-performance oil-water separation: Interface engineering design based on bioinspiration.

Frequent petrochemical spill accidents and secondary fire hazards have threatened the ecological environment and environmental safety. The traditional purification technology has the problems of high energy consumption and secondary pollution, which also brings new challenges to spill disposal. Herein, we demonstrate a biomimetic structure-based flame-retardant polyurethane (PU) sponge (FPUF@MOF-LDH@HDTMS) for continuous oil-water separation. Inspired by desert beetle and lotus leaf, the biomimetic micro-nano composite structure was constructed by in-situ growth of metal-organic framework-derived layered double hydroxide (MOF-LDH) on the surface of the PU sponge. After grafting MOF-LDH with hexadecyltrimethoxysilane, FPUF@MOF-LDH@HDTMS showed excellent superhydrophobic/superoleophilic performance (water contact angle=153° and oil contact angle=0°). FPUF@MOF-LDH@HDTMS can easily and quickly adsorb oily liquids suspended/settled in the water thanks to the unique bionic structure. FPUF@MOF-LDH@HDTMS has excellent oil/organic solvents absorption capacity; even after 20 cycles of use still maintains high adsorption capacity. More importantly, the continuous oil-water separation through FPUF@MOF-LDH@HTMS has achieved a separation efficiency of up to 99.1%. In addition, the bionic superhydrophobic sponge has excellent flame retardancy, which reduces the possibility of secondary fire caused by PU sponges. Thus, the biomimetic micro-nano composite structure provides a new design strategy for the more high-performance oil-water separation sponges.

p75NTR promotes tooth rhythmic mineralization via upregulation of BMAL1/CLOCK.

The circadian clock plays a critical role in dentomaxillofacial development. Tooth biomineralization is characterized by the circadian clock; however, the mechanisms underlying the coordination of circadian rhythms with tooth development and biomineralization remain unclear. The p75 neurotrophin receptor (p75NTR) is a clock factor that regulates the oscillatory components of the circadian rhythm. This study aims to investigate the impact of p75NTR on the rhythmic mineralization of teeth and elucidate its underlying molecular mechanisms. We generated p75NTR knockout mice to examine the effects of p75NTR deficiency on tooth mineralization. Ectomesenchymal stem cells (EMSCs), derived from mouse tooth germs, were used for in vitro experiments. Results showed a reduction in tooth mineral density and daily mineralization rate in p75NTR knockout mice. Deletion of p75NTR decreased the expression of DMP1, DSPP, RUNX2, and ALP in tooth germ. Odontogenic differentiation and mineralization of EMSCs were activated by p75NTR. Histological results demonstrated predominant detection of p75NTR protein in odontoblasts and stratum intermedium cells during rapid formation phases of dental hard tissue. The mRNA expression of p75NTR exhibited circadian variations in tooth germs and EMSCs, consistent with the expression patterns of the core clock genes Bmal1 and Clock. The upregulation of BMAL1/CLOCK expression by p75NTR positively regulated the mineralization ability of EMSCs, whereas BMAL1 and CLOCK exerted a negative feedback regulation on p75NTR by inhibiting its promoter activity. Our findings suggest that p75NTR is necessary to maintain normal tooth biomineralization. Odontogenic differentiation and mineralization of EMSCs is regulated by the p75NTR-BMAL1/CLOCK signaling axis. These findings offer valuable insights into the associations between circadian rhythms, tooth development, and biomineralization.

Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial.

BACKGROUND: The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in China. METHODS: This was an open-label, single-arm, phase 2 trial. Patients with potentially resectable ESCC (cT1b-3, Nany, M0 or T4a, N0-1, or M0) received preoperative intravenous sintilimab plus triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1) every 3 weeks for two cycles. The primary endpoints were safety and surgical feasibility; the secondary endpoint was major pathological response (MPR) rate. Genomic biomarkers (genetic mutations, tumor mutational burden (TMB), circulating tumor DNA status and immune microenvironment) in baseline tumor samples were investigated. RESULTS: All 30 patients completed two cycles of neoadjuvant treatment and underwent surgical resection. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 36.7% (11/30) of patients. The most frequent TRAEs were decreased white cell count (76.7%), anemia (76.7%), and decreased neutrophil count (73.3%). All TRAEs were hematological toxicities; none caused ≥30 days surgical delay. The MPR and pathological complete response (pCR) rates were 50.0% (15/30; 95% CI 33.2 to 66.9) and 20.0% (6/30; 95% CI 9.5 to 37.3), respectively. Patients with higher TMB and more clonal mutations were more likely to respond. ERBB2 alterations and ctDNA high-releaser status have a negative correlation with neoadjuvant ICI response. No significant difference was observed between therapeutic response and tumor immune microenvironment. CONCLUSIONS: Neoadjuvant sintilimab plus platinum-based triplet chemotherapy appeared safe and feasible, did not delay surgery and induced a pCR rate of 20.0% in patients with potentially resectable ESCC. TRIAL REGISTRATION NUMBER: NCT03946969.

Analysis of Clinical Characteristics of Connective Tissue Disease-Associated Interstitial Lung Disease in 161 Patients: A Retrospective Study.

Objective: This study was conducted to retrospectively analyze the clinical characteristics of CTD-ILD patients to provide strategies for clinical management. Methods: This study collected and analyzed the clinical data and relevant examination results of 161 patients diagnosed with CTD-ILD between 01 January 2018 and 01 January 2021. Results: A total of 161 CTD-ILD patients, 74.53% were females and 25.47% were males, 32.92% were elderly and 67.08% were non-elderly. The main clinical symptoms of CTD-ILD patients were cough (44.72%), decreased activity tolerance (40.37%). RA-ILD was the most common one in the non-elderly and the elderly CTD-ILD patients (48.15% and 50.94%, respectively). Compared with non-elderly, elderly patients with CTD-ILD had a longer duration of CTD (p=0.04). However, fatigue (p=0.005), activity tolerance (p=0.029), the incidence of pulmonary diffusion dysfunction (p=0.047), and systemic immunoinflammatory index (SII, p=0.014) (platelet × NLR) were all decreased. The standard deviation of red blood cell distribution width (RDW) (p=0.024) and immunoglobulin (IgA) (p=0.033) was significantly increased. The smoking index was significantly higher in men than in women with CTD-ILD (p=0.000), but symptoms of reduced activity tolerance were less pronounced than in women (p<0.05). Elderly CTD-ILD patients (p=0.003) and women from non-elderly patients were prone to lower hemoglobin (p=0.000). Among the elderly, the lymphocyte ratio was more significantly elevated in female CTD-ILD patients than in males (p=0.018). In contrast, neutrophil to lymphocyte ratio (NLR) and SII were lower in female (p=0.038) than in male CTD-ILD patients (p=0.043). Conclusion: CTD-ILD mainly affects non-elderly and women. Age may not be involved with decreased activity tolerance and increased lung function impairment in CTD-ILD patients. However, the elderly patients with CTD-ILD, especially the elderly female patients with low inflammation levels and high immune disorders, have a poor prognosis.

Pulmonary hypertension secondary to seronegative rheumatoid arthritis overlapping antisynthetase syndrome: A case report.

BACKGROUND: Polyarthritis is the most frequent clinical manifestation in antisynthetase syndrome (ASS) forms of idiopathic inflammatory myositis and may be misdiagnosed as rheumatoid arthritis (RA), particularly in patients with seronegative RA (SNRA). It is unclear whether there is an overlap between ASS and RA, or if ASS sometimes mimics RA. Pulmonary hypertension (PAH) is common in connective tissue diseases (CTDs). However, published reports on CTD-PAH do not include overlapping CTDs, and its incidence and impact on patient prognosis are unclear. CASE SUMMARY: We report the case of a 63-year-old woman who presented with a 3-mo history of symptom aggravation of recurrent symmetrical joint swelling and pain that had persisted for over 10 years. The patient was diagnosed with RA and interstitial lung disease. The patient repeatedly presented to the hospital's respiratory and rheumatology departments with arthralgia, plus shortness of breath after activity. Relevant tests indicated that anti-CCP and RF remained negative, while anti-J0-1 and anti-Ro-52 were strongly positive. It was not until recently that we recognized that this could be an unusual case of SNRA with concurrent ASS. Joint pain was relieved after regular anti-rheumatic treatment. Chest computed tomography scans showed that pulmonary interstitial changes did not progress significantly over several years; however, they showed gradual widening of the pulmonary artery, and cardiac ultrasound indicated elevated pulmonary artery systolic pressure. The prescribed treatment of PAH was not effective in improving shortness of breath. CONCLUSION: Overlap of RA and ASS may be missed. Further research is necessary to facilitate early diagnosis, effective evaluation, and prognosis.

A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development.

Objective: Tooth morphogenesis and the formation of hard tissues have been reported to be closely related to circadian rhythms. This study investigates the spatiotemporal expression and relationship of p75NTR with core clock genes, mineralization-related or odontogenesis-related genes, and aims to derive the potential role of p75NTR in regulating circadian rhythm and incrementality growth line formation during tooth development. Materials and methods: The dynamic morphology of the rat dental germ was observed at seven stages (E14.5 d, E16.5 d, E18.5 d, P.N. 4 d, P.N. 7 d, P.N. 10 d, and P.N. 15 d). Next, the expressions of p75NTR and other target factors were traced. The ectomesenchymal stem cells (EMSCs) were isolated from the E18.5d rat dental germs and synchronized using 50% of fetal bovine serum. Then, they were cultured in light/light (L.L.), dark/dark (D.D.), and light/dark (L.D.) conditions for 48 h. The total RNA was collected every 4 h, and the circadian rhythm dynamics of target factors were observed. To reveal the mechanism further, p75NTR was down-regulated in p75NTR ExIII-/- mice and up-regulated in immortalized mouse dental apical papilla progenitor cells. The change tendencies of other target factors were also detected. Results: The clock genes Bmal1, Clock, Per1, and Per2 were all expressed in tooth germs before the formation of dental hard tissues and demonstrated a regular oscillating expression pattern in EMSCs from dental germs. Their expression was affected by the L.D. stimulus, and most of them were promoted by D.D. conditions. p75NTR presented a similar expression pattern and a positive or negative relationship with most clock genes, mineralization-related and odontogenesis-related factors, such as brain and muscle ARNT-like protein-1 (Bmal1), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), MSH-like 1 (MSX1), dentin matrix acidic phosphoprotein 1 (Dmp1), and dentin sialophosphoprotein (Dspp). Moreover, the arrangement, morphology, and even boundary in pre-odontoblast/pre-ameloblast layers were disordered in the p75NTR ExIII-/- mice. Conclusion: Circadian rhythm was found to affect tooth development. p75NTR might play a crucial role in regulating clock genes in the mineralization and formation of the dental hard tissues. p75NTR is actively involved in the odontoblast-ameloblast junction and cell polarity establishment during tooth morphogenesis.

Efficient electro-Fenton catalysis by self-supported CFP@CoFe2O4 electrode.

In this work, the bimetallic iron oxide self-supported electrode was prepared by a simple solvothermal as well as thermal method. CoFe2O4 magnetic nanoparticles were grown in situ on the CFP surface and characterized to reveal the morphology, composition, and electrochemical properties of the electrode. Compared to CFP and CFP@Co-Fe, CFP@CoFe2O4 equipped more efficient mineralization current efficiency and lower energy consumption due to the improved electrocatalytic capacity of CoFe2O4 properly grown on the conductive substrate surface. Further studies showed that the manufactured electrode maintained a high level of stability after continuous operation. According to the free radical trapping experiment, EPR, and liquid mass spectrometry analysis, the rational reaction mechanism of p-nitrophenol was finally proposed, in which ·OH and SO4·- were considered as the main active oxidants. This work demonstrated the great potential of establishing an electro-Fenton system based on CoFe2O4 immobilized self-supporting cathode for environmental remediation.

CXCL10-armed oncolytic adenovirus promotes tumor-infiltrating T-cell chemotaxis to enhance anti-PD-1 therapy.

Resistance remains an obstacle to anti-programmed cell death protein 1 (PD-1) therapy in human cancer. One critical resistance mechanism is the lack of T cell chemotaxis in the tumor microenvironment (TME). CXCL10-CXCR3 signaling is required for T cell tumor infiltration and tumor immunotherapy. Oncolytic viruses (OVs), including oncolytic adenoviruses (AdVs), induce effective T cell immunity and tumor infiltration. Thus, arming OV with CXCL10 would be an attractive strategy to overcome resistance to anti-PD1 therapy. Here, we successfully constructed a novel recombinant oncolytic adenovirus encoding murine CXCL10, named Adv-CXCL10. Through intratumoural injection, the continuous expression of the functional chemokine CXCL10 in the TME is realized to recruit more CXCR3+ T cells into the TME to kill tumor cells, and the recombinant adenovirus shows great power to 'fire up' the TME and enhance the antitumour efficiency of PD-1 antibodies.

A Pan-Cancer Analysis of Predictive Methylation Signatures of Response to Cancer Immunotherapy.

Recently, tumor immunotherapy based on immune checkpoint inhibitors (ICI) has been introduced and widely adopted for various tumor types. Nevertheless, tumor immunotherapy has a few drawbacks, including significant uncertainty of outcome, the possibility of severe immune-related adverse events for patients receiving such treatments, and the lack of effective biomarkers to determine the ICI treatments' responsiveness. DNA methylation profiles were recently identified as an indicator of the tumor immune microenvironment. They serve as a potential hot spot for predicting responses to ICI treatment for their stability and convenience of measurement by liquid biopsy. We demonstrated the possibility of DNA methylation profiles as a predictor for responses to the ICI treatments at the pan-cancer level by analyzing DNA methylation profiles considered responsive and non-responsive to the treatments. An SVM model was built based on this differential analysis in the pan-cancer levels. The performance of the model was then assessed both at the pan-cancer level and in specific tumor types. It was also compared to the existing gene expression profile-based method. DNA methylation profiles were shown to be predictable for the responses to the ICI treatments in the TCGA cases in pan-cancer levels. The proposed SVM model was shown to have high performance in pan-cancer and specific cancer types. This performance was comparable to that of gene expression profile-based one. The combination of the two models had even higher performance, indicating the potential complementarity of the DNA methylation and gene expression profiles in the prediction of ICI treatment responses.

Analysis of Incidence and Clinical Characteristics of RSV Infection in Hospitalized Children: A Retrospective Study.

OBJECTIVE: To investigate the incidence and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection, and to provide evidence for the importance of preventive strategies and improvements in supportive care of RSV infection. METHODS: This retrospective study included children under 14 years who received throat swab test and were diagnosed with RSV infection from January 2019 to December 2020. Throat swabs and intravenous blood were the main sources of samples, which were obtained within 24 hours of hospitalization. Direct immunofluorescence assay was used to diagnose RSV infection. RESULTS: Among the 448 hospitalized children with RSV infection, males (71.9%) showed the highest proportion, the highest incidence was found in children<6 months old (45.3%), and 76.6% of them had pneumonia. Pharyngeal redness, cough, expectoration, and mental fatigue were the most common symptoms in hospitalized children of all ages. More than 60% of hospitalized children had increased lymphocyte count, aspartate aminotransferase, creatine kinase-MB form, lactate dehydrogenase, and α-HBDH levels. The rates of myocardial damage, respiratory failure, stay in the intensive care unit (ICU), use of mechanical ventilation, and absorption of oxygen were higher in children<6 months old. Except for children who were 37-60 months old, the percentage of length of hospital stay≥7 days in the other age groups was greater than 62.0%. Except for children who were 0-28 days old and>61 months old, the other age groups showed a re-hospitalization situation due to re-infection with RSV. In hospitalized children diagnosed with RSV infection from throat swabs, we also performed the RSV IgM test and found that 59.2% of them were positive, 8.0% of them were weakly positive, and 32.8% of them were negative. CONCLUSION: This study analyzes the incidence and clinical characteristics of hospitalized children with RSV infection, which provides evidence for the importance of preventive strategies and improvements in supportive care of RSV infection.

Correlation of Serum Adropin Levels with Risk Factors of Cardiovascular Disease in Hemodialysis Patients.

Background: Many preclinical studies have shown that adropin has physiological effects such as regulating glucose, lipid, and energy metabolism, protecting endothelial cells and antiatherosclerosis. Our aim is to explore whether adropin is correlated with risk factors of cardiovascular disease (CVD) in hemodialysis (HD) patients. Methods: We recruited 170 HD patients and 120 healthy controls. The serum adropin concentration and clinical characteristics were measured. Results: The serum adropin concentration in HD patients was significantly lower than that in healthy controls and which in HD patients with CVD or diabetes mellitus (DM) was significantly lower than that in patients without CVD or DM. The correlation analysis showed that serum adropin levels were correlated negatively with Age, CVD history, DM history, C-reactive protein, type B natriuretic peptide, phosphorus, intact parathyroid hormone, carotid artery plaque amount and carotid intima-media thickness (CIMT), left ventricular septal thickness (LVSTd), and left ventricular posterior wall thickness, whereas it was correlated positively with albumin, hemoglobin, serum creatinine and Kt/V, and ejection fraction value. Partial correlation analysis verified that serum adropin levels were correlated negatively with CIMT, and multiple linear regression analysis revealed that low serum adropin levels may be one independent predictors of CIMT. However, the partial correlation analysis and multiple linear regression analysis did not identify the significant correlation between serum adropin levels and LVSTd. Conclusions: Our study revealed that serum adropin level is significantly correlated with risk factors of CVD and low serum adropin levels may be a potential predictor of CVD in HD patients.

Role of cardiopulmonary bypass and arrested heart status in the early cell distribution after intracoronary infusion of bone marrow stromal cells.

BACKGROUND: Systemic distribution of bone marrow stromal cells (BMSCs) after intracoronary infusion (ICI) and the role of cardiopulmonary bypass (CPB) in cell distribution still remain unclear. This study was designed o analyze the cell distribution after ICI in variations of heart status in a swine myocardial infarction model. MATERIALS AND METHODS: After inducing a myocardial infarction, iron oxide labeled male cells (1 x 10(8)) were infused through the coronary artery of the beating swine heart in Group 1. In Group 2, CPB was set up and then the same volume of cells was infused after cardioplegic arrest. In Groups 3 and 4, the animals underwent either beating or arrested ICI with the same volume of saline. Three days later, cell distribution was assessed by T2* change with magnetic resonance imaging and sex-determining region on Y-chromosome with quantitive polymerase chain reaction. RESULTS: Only a few transplanted cells were localized in the heart and no difference was found between Groups 1 and 2. The majority of BMSCs would be trapped in extracardial organs, and more cells resided in the spleen in arrested heart status. CONCLUSIONS: The majority of BMSCs transplanted by ICI would be entrapped by the extracardial organs. The arrested heart with CPB during ICI does not favor more cell retention in the injured myocardium. The optimal approach of delivery of BMSCs still needs further investigation.