Potential-Regulated Design for Direct Recycling of Degraded LiFePO4 Cathode.

The rapid proliferation of power sources equipped with lithium-ion batteries poses significant challenges in terms of post-scrap recycling and environmental impacts, necessitating urgent attention to the development of sustainable solutions. The cathode direct regeneration technologies present an optimal solution for the disposal of degraded cathodes, aiming to non-destructively re-lithiate and straightforwardly reuse degraded cathode materials with reasonable profits and excellent efficiency. Herein, a potential-regulated strategy is proposed for the direct recycling of degraded LiFePO4 cathodes, utilizing low-cost Na2SO3 as a reductant with lower redox potential in the alkaline systems. The aqueous re-lithiation approach, as a viable alternative, not only enables the re-lithiation of degraded cathode while ignoring variation in Li loss among different feedstocks but also utilizes the rapid sintering process to restore the cathode microstructure with desirable stoichiometry and crystallinity. The regenerated LiFePO4 exhibits enhanced electrochemical performance with a capacity of 144 mA h g-1 at 1 C and a high retention of 98% after 500 cycles at 5 C. Furthermore, this present work offers considerable prospects for the industrial implementation of directly recycled materials from lithium-ion batteries, resulting in improved economic benefits compared to conventional leaching methods.

Comparison of the Ultrasound-Guided Supraclavicular and Infraclavicular Approaches for Subclavian Vein Cannulation in Children With Congenital Heart Disease.

OBJECTIVES: Central venous catheterization is used widely in critical pediatric patients. The authors sought to compare the success rate and safety of ultrasound-guided subclavian vein cannulation performed via infraclavicular and supraclavicular approaches. DESIGN: The authors compared the success rate of the first puncture and other information for cannulation in the children with congenital heart disease requiring central venous catheterization who were assigned randomly to the supraclavicular approach group (group A) or infraclavicular approach group (group B). SETTING: Medical university hospital pediatric cardiac intensive care units. PARTICIPANTS: Pediatric patients diagnosed with congenital heart disease in the preoperative period who were admitted to the cardiac intensive care unit and required subclavian vein catheterization. INTERVENTIONS: Ultrasound-guided subclavian vein cannulation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven children were included in the study, with 32 in group A and 35 in group B. Notably, there was a significant difference in the success rate of the first puncture between groups A and B (90.6% v 71.4, %, p = 0.047). Furthermore, the access time in group A was 11.8 seconds (3.2-95), which was significantly shorter than that in group B (16.0 [6.5-227] seconds, p = 0.001). In addition, the catheter malposition rate in group A was significantly lower than that in group B (0% v 11.4%, p = 0.049). Conversely, there were no significant differences in the total access time, overall success rate, and complications (eg, pneumothorax, hemorrhage, puncture artery, and nerve injury) between the 2 groups. CONCLUSIONS: For children with congenital heart disease requiring central venous catheterization during the perioperative period, the subclavian vein is a feasible site for catheterization. The supraclavicular approach, especially the left side, has a higher first-puncture success rate, shorter access time, lower complications, and a trend of lower incidence of catheter malposition. However, a larger sample size of a randomized controlled study is expected to verify the advantages of ultrasound-guided subclavian catheterization in children.

Nebulized Budesonide Prevents Airway Inflammation in Children with High Total IgE Levels After Open Heart Surgery with Cardiopulmonary Bypass: A Prospective Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) is a crucial technique used to repair congenital heart defects (CHD); however, it may induce inflammatory response, leading to airway inflammation and need for prolonged mechanical ventilation. In this study, we aimed to evaluate the effect of budesonide nebulization in children with high serum total immunoglobulin E (tIgE) levels undergoing surgical repair of CHD via CPB. We conducted a randomized, single-center, controlled trial at a tertiary teaching hospital. One-hundred and one children with high tIgE were enrolled and randomized into the budesonide nebulization group (BUD group, n = 50) or the normal saline nebulization group (NS group, n = 51) between January 2020 and December 2020. Budesonide or normal saline was administered through a vibrating mesh nebulizer during mechanical ventilation every 8 h. Blood and bronchoalveolar lavage fluid (BALF) samples were examined and data on airway mechanics and clinical outcomes were recorded. IL-6 and IL-8 levels in the blood and BALF samples significantly increased after CPB in both groups. Budesonide inhalation reduced IL-6 and IL-8 levels in the blood and BALF samples in children with high tIgE (P < 0.05). The mean airway pressure, PCO2, and oxygen index in the BUD group were significantly lower than those in the NS group after the first inhalation dose and persisted until almost 24 h after surgery. The peak inspiratory pressure and drive pressure were lower in the BUD group than in the NS group at nearly 24 h after surgery, with no significant difference at other time points. Additionally, the duration of mechanical ventilation, number of noninvasive ventilations after extubation, and number of patients using aerosol-inhaled bronchodilators after CICU in the BUD group were significantly lower than those in the NS group (P < 0.05). Children with high preoperative tIgE levels are at risk of airway inflammation after cardiopulmonary bypass. Inhaling budesonide during postoperative mechanical ventilation can reduce the intensity of inflammatory reactions, shorten the duration of mechanical ventilation, reduce airway pressure and the utilization of NIV after extubation.

Utilizing Spontaneous Ventilation Modes in Patients Underwent Corrective Surgery for Right Ventricular Outflow Tract Obstructive Congenital Heart Disease: A Crossover Study.

Background: This study aimed to determine whether the hemodynamics of patients with right ventricle outflow tract obstructive congenital heart disease (RVOTO-CHD) improve after corrective surgery by changing the ventilation mode. Methods: Patients with RVOTO-CHD who underwent corrective surgery were enrolled in this study. Echocardiography and advanced hemodynamic monitoring were performed using the pulse indicator continuous cardiac output (PiCCO) technology in the pressure-regulated volume control (PRVC) mode, followed with switching to the pressure support ventilation (PSV) mode and neurally adjusted ventilatory assist (NAVA) mode in random order. Results: Overall, 31 patients were enrolled in this study from April 2021 to October 2021. Notably, changing the ventilation mode from PRVC to a spontaneous mode (PSV or NAVA) led to better cardiac function outcomes, including right ventricular cardiac index (PRVC: 3.19 ± 1.07 L/min/ m 2 vs. PSV: 3.45 ± 1.32 L/min/ m 2 vs. NAVA: 3.82 ± 1.03 L/min/ m 2 , p < 0.05) and right ventricle contractility (tricuspid annular peak systolic velocity) (PRVC: 6.58 ± 1.40 cm/s vs. PSV: 7.03 ± 1.33 cm/s vs. NAVA: 7.94 ± 1.50 cm/s, p < 0.05), as detected via echocardiography. Moreover, in the NAVA mode, PiCCO-derived cardiac index (PRVC: 2.92 ± 0.54 L/min/ m 2 vs. PSV: 3.04 ± 0.56 L/min/ m 2 vs. NAVA: 3.20 ± 0.62 L/min/ m 2 , p < 0.05), stroke volume index (PRVC: 20.38 ± 3.97 mL/ m 2 vs. PSV: 21.23 ± 4.33 mL/ m 2 vs. NAVA: 22.00 ± 4.33 mL/ m 2 , p < 0.05), and global end diastolic index (PRVC: 295.74 ± 78.39 mL/ m 2 vs. PSV: 307.26 ± 91.18 mL/ m 2 vs. NAVA: 323.74 ± 102.87 mL/ m 2 , p < 0.05) improved, whereas extravascular lung water index significantly reduced (PRVC: 16.42 ± 7.90 mL/kg vs. PSV: 15.42 ± 5.50 mL/kg vs. NAVA: 14.4 ± 4.19 mL/kg, p < 0.05). Furthermore, peak inspiratory pressure, mean airway pressure, driving pressure, and compliance of the respiratory system improved in the NAVA mode. No deaths were reported in this study. Conclusions: We found that utilizing spontaneous ventilator modes, especially the NAVA mode, after corrective surgery in patients with RVOTO-CHD may improve their right heart hemodynamics and respiratory mechanics. However, further randomized controlled trials are required to verify the advantages of spontaneous ventilation modes in such patients. Clinical Trial Registration: NCT04825054.

MiR-29a-3p inhibits high-grade transformation and epithelial-mesenchymal transition of lacrimal gland adenoid cystic carcinoma by targeting Quaking.

BACKGROUND: Lacrimal adenoid cystic carcinoma (LACC) is the most common orbital malignant epithelial neoplasm. LACC with high-grade transformation (LACC-HGT) has higher rates of recurrence, metastasis, and mortality than LACC without HGT. This study investigated the effects of microRNA-29a-3p (miR-29a-3p) in the pathogenesis of LACC-HGT. METHODS: An Agilent human miRNA microarray was used to screen the differentially expressed miRNAs (DEMs) in LACC and LACC-HGT tumor tissues. Then, the primary cells obtained in previous studies were used to determine the effect of miR-29a-3p. RESULTS: The expression of miR-29a-3p was abnormally lower in LACC-HGT than in LACC. miR-29a-3p can specifically target the 3' UTR of Quaking mRNA and down-regulate Quaking expression, thereby inhibiting the proliferation, migration, and epithelial-mesenchymal transition of LACC cells. CONCLUSIONS: This study illustrated that miR-29a-3p functions as a tumor suppressor by down-regulating the expression of Quaking to inhibit the tumorigenesis of LACC cells. This study may also reveal the pathogenesis of HGT in LACC cells and provide a reference for LACC-HGT targeted diagnosis.

Nitrogen-doped carbon decorated 3D NiCoSe2 micro-flowers as high-performance anode materials for lithium-ion batteries.

Compared with monometallic selenides, bimetallic selenides have better synergistic effects and more abundant active sites for electrochemical reactions. As an important member of the transition metal oxide family, NiCoSe2 has been widely used in energy storage devices and has shown excellent electrochemical performance. So in this paper, nitrogen-doped carbon decorated NiCoSe2 composites (NiCoSe2/NC-700, NiCoSe2/NC-800, and NiCoSe2/NC-900) with a microflower structure were synthesized by calcining nickel-cobalt bimetallic organic skeleton materials at different temperatures, and were used as anode materials for rechargeable lithium-ion batteries. Because the MOF precursor has many advantages such as structural controllability, and a bimetal synergistic effect, the test results showed that the prepared NiCoSe2/NC composites have a special morphology, outstanding electrical conductivity, excellent lithium storage performance and electrochemical cycling performance in the process of being used as anode materials for lithium-ion batteries. The NiCoSe2/NC-800 materials displayed a high initial capacity (2099.8/1084.3 mA h g-1), and still maintained a high capacity (1041.2/989.9 mA h g-1) after 100 cycles at a current density of 0.1 A g-1 and in the voltage range of 0.01-3.0 V. In addition, at high current densities of 0.5 A g-1 and 1.0 A g-1, the increased capacity of NiCoSe2/NC composites may be due to the activation of electrodes and the pseudocapacitance during cycling. Through ex situ XRD experiments, the lithium storage mechanism of the NiCoSe2/NC-800 electrode material during cycling was further studied, and NiCoSe2/NC-800 was continuously converted into Ni, Co, and Li2Se during cycling.

New Insight on K2 Zn2 V10 O28 as an Advanced Cathode for Rechargeable Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) have recently attracted people's extensive attention in their application in energy storage systems resulting from their exclusive characteristics of low cost and environmental compatibility. However, finding suitable cathode materials continues to be the major challenge. Polyoxovanadates (POVs), as an important branch of polyoxometalates (POMs), are considered as a promising electrode material for reversible aqueous ZIBs relying on the flexible valence state of V. Herein, POVs (K2 Zn2 V10 O28 : KZVO) are reported as an advanced cathode for storing Zn2+ , which delivers a high discharge capacity of 223.4 mAh g-1 at 0.1 A g-1 , considerable energy density (182.9 Wh kg-1 ) and power density (40.38 W kg-1 ), and robust cyclic performance. In addition, the dynamic properties of the KZVO/Zn battery are revealed by pseudocapacitance analysis and GITT tests. Meanwhile, the storage mechanism of Zn2+ is further analyzed by ex situ XRD, XPS, TEM, and HRTEM. Overall, this work not only draws up a cathode material for the POMs system in aqueous ZIBs, but also demonstrates that POMs are the rising star in energy storage and electric energy applications.

Investigating the natural history and prognostic nature of NTRK gene fusions in solid tumors.

BACKGROUND: Several TRK inhibitors have demonstrated clinical efficacy in patients with solid tumors harboring NTRK gene fusions. However, the natural history and prognostic implications of NTRK fusions in solid tumors remain unknown. METHODS: A cohort of 77 MD Anderson Cancer Center patients (MDACC) with NTRK gene fusions was identified and retrospectively compared to a second cohort from the Cancer Genome Atlas (TCGA) database. Due to paucity of events in early stage cancers and lack of TCGA data in rare tumors, 25 randomly selected MDACC patients were matched to 122 TCGA patients without NTRK gene fusion. Next we assessed the associations between NTRK gene fusion and overall (OS) and progression-free survivals (PFS). RESULTS: Among the 77 MDACC patients with NTRK gene fusions, 18 NTRK fusion partners were identified. There were insufficient OS events for analysis in the matched cohort. PFS was not significantly different (p = 0.49) between the NTRK-fusion positive MDACC patients (median PFS 786 weeks, 95% CI 317-NE) and the NTRK-fusion negative TCGA patients (median PFS NE). The adjusted hazard ratio comparing TCGA patients to MDACC patients was HR = 0.72 (95% CI: 0.23-2.33), which trended towards a reduced rate of progression or death experienced by TCGA patients. CONCLUSIONS: This study did not identify statistically significant associations between NTRK fusion and PFS. Nonsignificant trends estimated increases in the risk of progression or death events for patients with NTRK fusions when compared to matched controls. Our findings help illuminate the influence of NTRK fusions on the natural history of a variety of solid tumors.

Establishment of a human meibomian gland carcinoma cell model and analysis of differently expressed genes.

Meibomian gland carcinoma (MGC) is a malignant eyelid tumor with a high malignancy degree and poor prognosis. However, the lack of suitable cell and animal models has limited the study of MGC pathogenesis. In the present study, we established and identified one human MGC cell and one meibomian gland (MG) cell model by fresh surgical resection tissue block primary culture and differentially expressed gene assays. The outgrowth of MGC and MG cells was periodically observed after primary culture, and the first passage of MGC cells proceeded on the 14th day, whereas that for MG cells after three weeks. Cell ultrastructures were observed by transmission electron microscopy (TEM). Immunofluorescence staining showed that MGC and MG cells were both positive for cytokeratin (CK) and androgen receptor (AR). Orange granules were observed in the cytoplasm of MGC and MG cells using Oil red O staining, but they were stronger for MG cells than for MGC. CCK-8 detection demonstrated that the proliferation ability of MGC cells was stronger than that of MG cells. Moreover, during RNA sequence analyses, 3023 differential expressed genes were detected between MGC and MG cells. These genes were involved in biological processes such as cell division and positive regulation of cell migration; the signaling pathways mainly covered cell cycle and DNA replication. Further, the tumorigenic potential of MGC cells was examined by inoculating them subcutaneously into the right abdomen of three severely immunodeficient NOD -SCID mice. Transplanted tumors formed on day 11 after inoculation. The xenograft mouse tissues retained the same histological characteristics as the human MGC original tumor and MGC primary cells. Altogether, these results showed that the MGC and MG models were successfully cultured and established, and differentially expressed genes were successfully detected. We provided a useful model and molecular basis for studying the biological characteristics and pathogenesis of human MGC.

Legumain affects the PI3K/AKT tumor progression pathway in retinoblastoma.

Known as a common malignant tumor among children, retinoblastoma (RB) is highly malignant and has poor prognosis, damages children's vision and degrades quality of life. To identify a potential molecular mechanism of RB, we conducted this study on legumain (LGMN), which is highly expressed in multiple tumors. In this study, we found that LGMN was significantly upregulated in RB cells and was positively expressed in RB tissues. We confirmed that LGMN overexpression (LGMN-OE) can promote RB cell proliferation and inhibit cell apoptosis through CCK8 experiments and flow cytometry. In addition, real-time quantitative polymerase chain reaction (RT‒qPCR) and Western blot results showed that LGMN-OE could regulate the expression of epithelial-mesenchymal transformation-related genes and proteins, related to tumor invasion and metastasis. Moreover, after LGMN knock down, the result was the opposite., RNA sequence analysis revealed 1159 differentially expressed genes between LGMN-OE and the negative control (NCOE), of which 564 were upregulated and 595 were downregulated. The first 10 genes were verified by RT‒qPCR based on P value and fold change. Interestingly, we found that LGMN could regulate the expression of recoverin (RCVRN)through a gene responsible for cancer-related retinopathy. We also screened and verified that LGMN partially activated the PI3K/AKT pathway in RB. Furthermore, we evaluated the effect of legumain inhibitors (e.g., esomeprazole) on RB, and the results suggest that esomeprazole may provide a reference for the clinical adjuvant treatment of RB. In conclusion, legumain can serve as an attractive target for RB therapy and hopefully provide new insights and ideas for the development of targeted drugs and precise personalized clinical therapy.

AKT2 identified as a potential target of mir-29a-3p via microRNA profiling of patients with high proliferation lacrimal gland adenoid cystic carcinoma.

The lacrimal gland adenoid cystic carcinoma (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in high proliferation LACC(HP-LACC) compared with low proliferation LACC(LP-LACC). In this study, miRNA microarray was used to explore the differentially expressed miRNAs profiling between HP-LACC and LP-LACC and its potential signaling pathway. Tissues from 17 patients with LACC were collected and made into tissue microarrays. Patients were divided into a high proliferation group and a low proliferation group based on Ki-67 value. HE, immunofluorescence (IF), and Immunohistochemistry (IHC) were performed on the tissue microarrays. Eight LACC tissues(4 HP-LACC and 4 LP-LACC) were made into miRNA microarrays and analyzed for miRNA profiles. Differentially expressed miRNAs were analyzed by volcano plot and heat map. Target gene were predicted using the miRWalk and miRDB for these differentially expressed miRNAs, the intersection of the results are used as targets for further gene ontology and KEGG pathway analysis.The four differentially expressed miRNAs were validated by qRT-PCR, the miRNAs with statistically significant differences validated by dual luciferase reporter and qRT-PCR. Finally, IHC was used for their downstream signaling pathway proteins.HE staining showed the presence of tubular, cribriform, and basaloid structures in LACC. IF showed the presence of CK7,P63 fluorescence expression in all three structures.Patients were divided into HP-LACC and LP-LACC based on Ki-67 median value of 11%. IHC and survival analysis showed with the increase of KI-67 ratio, the proportion of P63 decreased, and the expression of P53 increased. The disease-free survival and overall survival of the patients decreased. IHC and survival analysis showed as Ki-67 expression increased, P63 expression decreased, P53 expression elevated, with prognosis worse. Heat map and volcano plot yielded 15 differentially expressed miRNAs between HP-LACC and LP-LACC.The 15 differential miRNAs were used to predict target genes in miRWalk and miRDB databases respectively, and there were 559 target genes after intersection.559 predicted target genes obtained. Go and KEGG analysis showed that these target genes exerted important biological functions through multiple signaling pathways. Among the 15 differentially expressed miRNAs, miR-29a-3p was verified to be significant by qRT-PCR. Dual luciferase reporter and tissue microarray immunohistochemical assays validated that AKT2 was a direct target gene of miR-29a-3p. Current studies have identified differentially expressed miRNAs associated with LACCs of variable proliferation ability, and found that AKT2 is a direct target gene of miR-29a-3p, which will contribute to target gene therapy in patients with high proliferation LACC in the future.

Recent Developments and Challenges of Vanadium Oxides (Vx Oy ) Cathodes for Aqueous Zinc-Ion Batteries.

The rapid depletion of lithium resources and the increasing demand for electrical energy storage have stimulated the pursuit of emerging electrochemical energy storage. Aqueous zinc ion batteries (ZIBs) are highly sought after for their low cost, high safety, and increased environmental compatibility. However, the search for suitable cathode materials is still tricky for a wide range of researchers. Vanadium oxides (Vx Oy ), with their abundant vanadium valence, easily deformable V-O polyhedrons, and tunable chemical compositions, are of significant advantage in developing emerging materials. This work provides a detailed review of different Vx Oy for the application in aqueous ZIBs. The current problems and optimization strategies of Vx Oy cathode materials are systematically discussed. Finally, the current challenges and possible directions for future research of Vx Oy cathode materials in aqueous ZIBs are presented.

Exposure to traffic-related fine particulate matter 2.5 causes respiratory damage via peroxisome proliferator-activated receptor gamma-regulated inflammation.

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation. Peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to regulate inflammatory responses in diverse cell types. Therefore, this work investigated the mechanisms of PPARγ in regulating traffic-related PM2.5-induced airway inflammation. Using the diffusion flame burner soot generation, traffic-related PM2.5 was generated and adsorbed. BALB/c male mice and human bronchial epithelial cells (16-HBE) were exposed to PM2.5 alone or co-treatment with rosiglitazone (RSG), an agonist of PPARγ. To the end of exposure, bronchoalveolar lavage fluid (BALF), venous blood and arterial blood, trachea, bronchus and lung tissues were collected. The levels of IL-1ß, IL-6, and IL-17 were detected by ELISA, and the cell types in BALF were counted. Hematoxylin-eosin (H&E) assay were used to analyze the pathological conditions of lung, bronchus, and pulmonary artery. Apoptosis was detected by TUNEL, and PPARγ expression in lung and bronchus was detected by immunohistochemical (IHC) staining. Western Blot was used to detect PPARγ, NF-kB, AP-1 and STAT3 expression in lung and bronchus. The viability was detected by MTT method. PM2.5 exposure caused pathological damage to the lung, bronchus and pulmonary artery tissue, which induced apoptosis of bronchial epithelial cells. PM2.5 exposure caused local inflammation of the whole body and airway. PPARγ expression increased after PM2.5 exposure. PM2.5 exposure regulated the downstream signaling pathways to affect the inflammatory response through PPARγ. Exposure to traffic-related PM2.5 caused respiratory damage via PPARγ-regulated inflammation.

Discrimination and Characterization of the Volatile Organic Compounds in Schizonepetae Spica from Six Regions of China Using HS-GC-IMS and HS-SPME-GC-MS.

Volatile organic compounds (VOCs) are the main chemical components of Schizonepetae Spica (SS), which have positive effects on the quality evaluation of SS. In this study, HS-SPME-GC-MS (headspace solid-phase microextraction-gas chromatography-mass spectrometry) and HS-GC-IMS (headspace-gas chromatography-ion mobility spectrometry) were performed to characterize the VOCs of SS from six different regions. A total of 82 VOCs were identified. In addition, this work compared the suitability of two instruments to distinguish SS from different habitats. The regional classification using orthogonal partial least squares discriminant analysis (OPLS-DA) shows that the HS-GC-IMS method can classify samples better than the HS-SPME-GC-MS. This study provided a reference method for identification of the SS from different origins.

MIR3142HG promotes lipopolysaccharide-induced acute lung injury by regulating miR-450b-5p/HMGB1 axis.

The present study aimed to evaluate the potential roles of MIR3142HG, a novel long non-coding RNA (lncRNA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was simulated by the treatment of LPS in human pulmonary microvascular endothelial cells (HPMECs). The expression of MIR3142HG, miR-450b-5p and high-mobility group box 1 (HMGB1) was determined by real-time PCR and western blotting. Functional analysis was performed through the assessment of cell viability, apoptosis and the production of proinflammatory cytokines. The interactions among MIR3142HG, miR-450b-5p and HMGB1 were analyzed by bioinformatics methods, dual-luciferase reporter and RNA pull-down assays. Using gain- and loss-of-function approaches, the in vitro functions of MIR3142HG and miR-450b-5p were subsequently assessed. MIR3142HG expression was upregulated, while miR-450b-5p was decreased in LPS-treated HPMECs. MIR3142HG knockdown protected against ALI induced by LPS through alleviating the apoptosis and inflammation of HPMECs. MIR3142HG impaired miR-450b-5p-mediated inhibition of HMGB1. Besides, the effects of MIR3142HG silencing could be alleviated by miR-4262 inhibition or HMGB1 overexpression. MIR3142HG mediated LPS-induced injury of HPMECs by targeting miR-450b-5p/HMGB1, suggesting that MIR3142HG might serve as a therapeutic potential for the treatment of ALI.

Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2.

P53 is an apoptosis marker which is involved in determining nucleus pulposus (NP) cell fate. Little is known about P53 interaction with N-Myc downstream-regulated gene 2 (NDRG2) in intervertebral disc degeneration (IVDD). Here, we studied the role of the P53-NDRG2 axis in IVDD. We found that NDRG2 was expressed in NP tissue obtained from patients with IVDD. The level of NDRG2 was positively related to the severity of IVDD, as determined by Pfirrmann grading. Subsequently, we overexpressed NDRG2 in human NP cells by adenoviral transfection and studied the effects of increased levels of NDRG2 on the viability and apoptosis of these cells. NDRG2 overexpression induced NP cell apoptosis and reduced viability in NP cells obtained from patient with IVDD. We also found that the level of P53 was elevated in NP cells from patients with IVDD and treatment with exogenous P53 upregulated NDRG2 in NP cells. Last, IVDD model was established in P53 knockout mice and the pathological changes in the intervertebral discs and NDRG2 expression were examined. P53 knockout can reduce the damage of NP tissues after IVDD surgery to some extent. Restoration of NDRG2 antagonized the effect of P53 knockout on IVDD. Collectively, this study suggests that elevated P53 in NP cells stimulates apoptosis of the cells by upregulating NDRG2 expression, thereby exacerbating IVDD.

Dimeric Her2-specific affibody mediated cisplatin-loaded nanoparticles for tumor enhanced chemo-radiotherapy.

BACKGROUND: Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O2 production, which in turn serves as a "radiosensitizer" to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. RESULTS: Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (ZHer2) mediated cisplatin-loaded mesoporous polydopamine/MnO2/polydopamine nanoparticles (Pt@mPDA/MnO2/PDA-ZHer2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O2. ZHer2, produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of ZHer2. These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. CONCLUSIONS: The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics.

Elevated Arterial-Central Venous Carbon Dioxide Partial Pressure Difference Indicates Poor Prognosis in the Early Postoperative Period of Open Heart Surgery in Infants with Congenital Heart Disease.

BACKGROUND: Elevated arterial-central venous carbon dioxide partial pressure difference (AVCO2) may be an important marker to predict tissue and organ hypoperfusion in adults. We analyzed the hemodynamic data of infants with congenital heart disease who underwent corrective repair with cardiopulmonary bypass (CPB) to identify whether AVCO2 has clinical significance in early postoperative tissue hypoperfusion, occurrence of complications, and clinical outcomes. METHODS: Infants with clinical conditions of hypoperfusion, without volume responsiveness and with ineffective initial treatment, within 3 h of cardiac surgery were enrolled in this study. A pulse contour cardiac output catheter was used to monitor the cardiac index (CI). Eight measurements of arterial blood gas and central venous blood gas were taken within 42 h after surgery. Clinical data of all patients were recorded. RESULTS: A total of 69 children were enrolled in this study. Arteriovenous oxygen difference, AVCO2, lactic acid level, and vasoactive inotropic score in the hypoperfusion group (oxygen supply/oxygen consumption ratio [DO2/VO2] of ≤ 2) were significantly higher than those in the non-hypoperfusion group (DO2/VO2 > 2), while the CI in the hypoperfusion group was significantly lower than that in the non-hypoperfusion group. The cutoff value of AVCO2 to predict DO2/VO2 ≤ 2 was 12.3 within 42 h of surgery with area under the curve of 0.84. High AVCO2 is more likely to be associated with some complications and prolonged mechanical ventilation and length of stay in the intensive care unit. CONCLUSION: Elevated AVCO2 within 42 h of CPB in infants is associated with tissue and organ hypoperfusion and incidence of complications. Persistent or repeated increase in AVCO2 indicates poor prognosis.

[Clinical features of very preterm small-for-gestational-age infants born due to severe preeclampsia].

OBJECTIVE: To study the clinical features of very preterm small-for-gestational-age infants born by cesarean section due to severe preeclampsia. METHODS: Forty-two small-for-gestational-age infants who were admitted from August 2017 to July 2018 and were born due to severe preeclampsia were enrolled as the observation group. Forty very preterm infants who were born to healthy mothers since uterine contractions could not be suppressed were enrolled as the control group. Perinatal features, clinical manifestations of infection, complications, and clinical outcomes were analyzed for the two groups. RESULTS: Within 6 hours and 2-3 days after birth, the observation group had significantly lower white blood cell count (WBC), absolute neutrophil count (ANC), and platelet count (PLT) than the control group (P < 0.05). At 5-7 days after birth, there was no significant difference in WBC between the two groups (P > 0.05), while the observation group still had significantly lower ANC and PLT than the control group (P < 0.05). The observation group had a significantly higher C-reactive protein (CRP) level than the control group at 2-3 days and 5-7 days after birth (P < 0.05). The observation group had a significantly higher proportion of infants with severe infections than the control group (P < 0.05). The observation group had a significantly higher hemoglobin level than the control group within 6 hours after birth (P < 0.05). The observation group had a significantly higher incidence rate of bronchopulmonary dysplasia than the control group (P < 0.05). There was no significant difference between the two groups in the rate of pulmonary hemorrhage, intracranial hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, and the rate of use of invasive ventilation, and clinical outcomes (P > 0.05). CONCLUSIONS: Very preterm small-for-gestational-age infants born due to severe preeclampsia have a high incidence rate of infection and severe conditions. Early manifestations include reductions in the infection indicators WBC, ANC, and PLT, and CRP does not increase significantly in the early stage and gradually increases at 2-3 days after birth. Most of these infants require invasive ventilation after birth, with bronchopulmonary dysplasia as the main complication. Clinical changes should be closely observed and inflammatory indicators should be monitored for early identification of infection, timely diagnosis, and timely adjustment of antibiotic treatment, so as to improve the outcome.

Characteristics of Pulmonary Vascular Remodeling in a Porcine Model of Shunt-Associated Pulmonary Arterial Hypertension.

Lung biopsy is the gold standard for evaluating pathological changes in the pulmonary vascular bed. Knowing the distribution characteristics of pulmonary vascular lesions can improve the accuracy of lung biopsy. To investigate the distribution characteristics of pulmonary vascular remodeling, a reliable porcine model of shunt-associated pulmonary arterial hypertension (PAH) was established. Twenty piglets were randomly divided into the experimental group (n = 10) and the control group (n = 10). A modified Blalock-Taussig shunt (MBTS, left innominate artery to main pulmonary artery) was created surgically in the experimental group. Three months later, an invasive catheter was used to obtain hemodynamic parameters, and lung biopsy was performed to assess the remodeling of pulmonary vascular bed. MBTS was successfully implemented in six piglets. There's no significant difference in hemodynamic parameters of the two groups before the shunt. However, these parameters and right ventricular hypertrophy index of the experimental group were significantly increased after three months shunting. Pathological changes in the experimental group, including thickening of pulmonary artery media, intimal fibrosis, and right ventricular hypertrophy, were observed. Furthermore, the percentage of media thickness and medial area of the experimental group were significantly higher than control group. Histopathology showed that vascular remodeling of the lung was inhomogeneous and that the lateral lesion was more severe than other segments. These results indicated that MBTS could be used to establish a reliable porcine model of shunt-associated PAH and that multisite detection with different segments should be applied to assess the severity of pulmonary vascular remodeling.