Mefunidone ameliorates acute liver failure in mice by inhibiting MKK4-JNK pathway.

Acute liver failure (ALF) is a critical condition that can lead to substantial liver dysfunction. It is characterized by complex clinical manifestations and rapid progression, presenting significant challenges in diagnosis and treatment. We investigated the protective effect of mefunidone (MFD), a novel antifibrosis pyridone agent, on ALF in mice, and explored its potential mechanism of action. MFD pretreatment can alleviate lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced ALF, reduce hepatocyte apoptosis, and reduce inflammation and oxidative stress. Additionally, MFD alleviated LPS/D-GalN-stimulated reactive oxygen species (ROS) production and cell death in AML12 cells. RNA sequencing enrichment analysis showed that MFD significantly affected the Mitogen-Activated Protein Kinase (MAPK) pathway. In vivo and in vitro experiments showed that MFD inhibited MKK4 and JNK phosphorylation. JNK activation caused by MKK4 and JNK activators could eliminate the therapeutic effect of MFD on AML12. In addition, MFD pretreatment alleviated ConA-induced ALF, reduced inflammation and oxidative stress in mice, and reduced mouse mortality. These results suggest that MFD can potentially protect against ALF, partially by inhibiting the MKK4-JNK pathway, and is a promising new therapeutic drug for ALF.

The prognostic significance of POD24 in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. METHODS: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. RESULTS: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, ß2-microglobulin (ß2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. CONCLUSION: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.

Impact of endoplasmic reticulum stress on chondrocyte apoptosis in rat model of DDH.

Developmental dysplasia of the hip (DDH) is a developmental disorder characterized by acetabular dysplasia leading to early osteoarthritis. This study examines the role of endoplasmic reticulum stress (ERS) in chondrocyte apoptosis and cartilage degeneration within a DDH model. In the rat model of DDH, created using a swaddling technique, significant deformities in the femoral head and acetabulum were observed, alongside an upregulation of matrix metalloproteinase-13 in acetabular cartilage. We also noted increased levels of apoptosis and ERS-related factors in the acetabular cartilage of DDH models. Additionally, rat chondrocytes exposed to high-magnitude cyclic tensile strain (CTS, 1 Hz, 10% equibiaxial strain) in vitro exhibited elevated ERS and increased apoptosis. Importantly, treatment with the ERS inhibitor 4-phenylbutyric acid effectively suppressed apoptosis induced by CTS in chondrocytes. Our findings suggest that ERS contributes to the upregulation of apoptosis-related factors in chondrocytes within the DDH model, indicating the potential of ERS modulation as a therapeutic approach for DDH-related cartilage degeneration.

Integrated transcriptome and metabolome provide insight into flavonoid variation in goji berries (Lycium barbarum L.) from different areas in China.

Goji berries (Lycium barbarum L.) were rich in flavonoids, showing high nutritional and medicinal value. However, a thorough evaluation and comparison of the flavonoids in goji berries from various regions and the possible biological regulation pathways with differences are scanty. Here, we investigated the flavonoid metabolites and gene expression levels of goji berries from three major production areas in China using transcriptomics sequencing and metabolomics. The total flavonoid content and total polyphenol content of goji berry in Ningxia (57.87 µg/g and 183.41 µg/g, respectively) were higher than in Qinghai (50.77 µg/g and 156.81 µg/g) and Gansu (47.86 µg/g and 111.17 µg/g). We identified the 105 differentially accumulated flavonoids (DAFs) and 1858 differentially expressed genes (DEGs) from the goji berries in three habitats. Interestingly, gossypetin-3-O-rutinoside and isorhamnetin were significantly expressed between Ningxia and Qinghai berries. The chalcone isomerase (CHI), chalcone synthase (CHS), and flavonol synthase (FLS) genes also played key roles in the regulation of flavonoid synthesis. In addition, MYB1 positively regulated the expression of quercetin-3-O-glucoside, quercetin-7-O-glucoside and isohyperoside. As a result, we speculated that CHI, CHS, FLS genes, and related transcription factors jointly controlled the variation of flavone accumulation in goji berries. These findings may provide a new perspective for understanding the accumulation and molecular mechanisms of goji flavonoids.

Fluorofenidone protects against acute liver failure in mice by regulating MKK4/JNK pathway.

AIMS: Acute liver failure (ALF) is a life-threatening disease characterized by abrupt and extensive hepatic necrosis and apoptosis, resulting in high mortality. The approved drug, N-acetylcysteine (NAC), is only effective for acetaminophen (APAP)-associated ALF at the early stage. Thus, we investigate whether fluorofenidone (AKF-PD), a novel antifibrosis pyridone agent, protects against ALF in mice and explore its underlying mechanisms. METHODS: ALF mouse models were established using APAP or lipopolysaccharide/D-galactosamine (LPS/D-Gal). Anisomycin and SP600125 were used as JNK activator and inhibitor, respectively, and NAC served as a positive control. Mouse hepatic cell line AML12 and primary mouse hepatocytes were used for in vitro studies. RESULTS: AKF-PD pretreatment alleviated APAP-induced ALF with decreased necrosis, apoptosis, reactive oxygen species (ROS) markers, and mitochondrial permeability transition in liver. Additionally, AKF-PD alleviated mitochondrial ROS stimulated by APAP in AML12 cells. RNA-sequencing in the liver and subsequent gene set enrichment analysis showed that AKF-PD significantly impacted MAPK and IL-17 pathway. In vitro and in vivo studies demonstrated that AKF-PD inhibited APAP-induced phosphorylation of MKK4/JNK, while SP600125 only inhibited JNK phosphorylation. The protective effect of AKF-PD was abolished by anisomycin. Similarly, AKF-PD pretreatment abolished hepatotoxicity caused by LPS/D-Gal, decreased ROS levels, and diminished inflammation. Furthermore, unlike NAC, AKF-PD, inhibited the phosphorylation of MKK4 and JNK upon pretreatment, and improved survival in cases of LPS/D-Gal-induced mortality with delayed dosing. CONCLUSIONS: In summary, AKF-PD can protect against ALF caused by APAP or LPS/D-Gal, in part, via regulating MKK4/JNK pathway. AKF-PD might be a novel candidate drug for ALF.

CD86 Is Associated with Immune Infiltration and Immunotherapy Signatures in AML and Promotes Its Progression.

Background: Cluster of differentiation 86 (CD86), also known as B7-2, is a molecule expressed on antigen-presenting cells that provides the costimulatory signals required for T cell activation and survival. CD86 binds to two ligands on the surface of T cells: the antigen CD28 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). By binding to CD28, CD86-together with CD80-promotes the participation of T cells in the antigen presentation process. However, the interrelationships among CD86, immunotherapy, and immune infiltration in acute myeloid leukemia (AML) are unclear. Methods: The immunological effects of CD86 in various cancers (including on chemokines, immunostimulators, MHC, and receptors) were evaluated through a pan-cancer analysis using TCGA and GEO databases. The relationship between CD86 expression and mononucleotide variation, gene copy number variation, methylation, immune checkpoint blockers (ICBs), and T-cell inflammation score in AML was subsequently examined. ESTIMATE and limma packages were used to identify genes at the intersection of CD86 with StromalScore and ImmuneScore. Subsequently, GO/KEGG and PPI network analyses were performed. The immune risk score (IRS) model was constructed, and the validation set was used for verification. The predictive value was compared with the TIDE score. Results: CD86 was overexpressed in many cancers, and its overexpression was associated with a poor prognosis. CD86 expression was positively correlated with the expression of CTLA4, PDCD1LG2, IDO1, HAVCR2, and other genes and negatively correlated with CD86 methylation. The expression of CD86 in AML cell lines was detected by QRT-PCR and Western blot, and the results showed that CD86 was overexpressed in AML cell lines. Immune infiltration assays showed that CD86 expression was positively correlated with CD8 T cell, Dendritic cell, macrophage, NK cell, and Th1_cell and also with immune examination site, immune regulation, immunotherapy response, and TIICs. ssGSEA showed that CD86 was enriched in immune-related pathways, and CD86 expression was correlated with mutations in the genes RB1, ERBB2, and FANCC, which are associated with responses to radiotherapy and chemotherapy. The IRS score performed better than the TIDE website score. Conclusion: CD86 appears to participate in immune invasion in AML and is an important player in the tumor microenvironment in this malignancy. At the same time, the IRS score developed by us has a good effect and may provide some support for the diagnosis of AML. Thus, CD86 may serve as a potential target for AML immunotherapy.

Clinical Prognostic Factors and Integrated Multi-Omics Studies Identify Potential Novel Therapeutic Targets for Pediatric Desmoid Tumor.

BACKGROUND: Desmoid tumor (DT), also known as desmoid-type fibromatosis (DTF) or aggressive fibromatosis (AF) is a rare mesenchymal tumor affecting both children and adults. It is non-metastasis but infiltrative, growing with a high recurrence rate to even cause serious health problems. This study investigates the biology of desmoid tumors through integrated multi-omics studies. METHODS: We systematically investigated the clinical data of 98 extra-abdominal cases in our pediatric institute and identified some critical clinical prognostic factors. Moreover, our integrated multi-omics studies (Whole Exome Sequencing, RNA sequencing, and untargeted metabolomics profiling) in the paired PDT tumor/matched normal tissues identified more novel mutations, and potential prognostic markers and therapeutic targets for PDTs. RESULTS: The top mutation genes, such as CTNNB1 (p.T41A and p.S45F) and MUC4 (p.T3775T, p.S3450S, etc.), were observed with a mutation in more than 40% of PDT patients. We also identified a panel of genes that are classed as the FDA-approved drug targets or Wnt/ß-catenin signaling pathway-related genes. The integrated analysis identified pathways and key genes/metabolites that may be important for developing potential treatment of PDTs. We also successfully established six primary PDT cell lines for future studies. CONCLUSIONS: These studies may promote the development of novel drugs and therapeutic strategies for PDTs.

One-Step Synthesized Iron-Carbon Core-Shell Nanoparticles to Activate Persulfate for Effective Degradation of Tetrabromobisphenol A: Performance and Activation Mechanism.

Tetrabromobisphenol A (TBBPA), as an emerging endocrine disrupter, has been considered one of the persistent organic contaminants in water. It is urgently necessary to develop an efficient technique for the effective removal of TBBPA from water. Herein, a one-step hydrothermal synthesis route was employed to prepare a novel iron-carbon core-shell nanoparticle (Fe@MC) for effectively activating persulfate (PS) to degrade TBBPA. Morphological and structural characterization indicated that the prepared Fe@MC had a typical core-shell structure composed of a 5 nm thick graphene-like carbon shell and a multi-valence iron core. It can be seen that 94.9% of TBBPA (10 mg/L) could be degraded within 30 min at pH = 7. This excellent catalytic activity was attributed to the synergistic effect of the porous carbon shell and a multi-valence iron core. The porous carbon shell could effectively prevent the leaching of metal ions and facilitate PS activation due to its electron transfer capability. Furthermore, numerous micro-reaction zones could be formed on the surface of Fe@MC during the rapid TBBPA removal process. Radical quenching experiments and electron paramagnetic resonance (EPR) technology indicated that reactive oxygen species (ROS), including OH, SO4-, O2-, and 1O2, were involved in the TBBPA degradation process. Based on density functional theory (DFT) calculation, the carbon atoms linked by phenolic hydroxyl groups would be more vulnerable to attack by electron-rich groups; the central carbon was cracked and hydroxylated to generate short-chain aliphatic acids. The toxicity evaluation provides clear evidence for the promising application potential of our prepared material for the efficient removal of TBBPA from water.

Ionothermal-Transformation Strategy to Synthesize Hierarchically Tubular Porous Single-Iron-Atom Catalysts for High-Performance Zinc-Air Batteries.

Inexpensive carbon-based nitrogen-coordinated iron single-atom catalysts (CN-FeSACs) have been recently demonstrated as the most promising platinum substitutions for boosting the sluggish oxygen electrode performance in fuel cells and metal-air batteries. However, it is still a great challenge to develop economical and effective CN-FeSACs satisfying the needs of high output power. Herein, an ionothermal-transformation strategy is proposed to synthesize hierarchically tubular porous CN-FeSACs with an ultrahigh special surface area of 2500 m2 g-1 to host abundant single-atom iron sites with an attempt to simultaneously boost sluggish oxygen reduction reaction (ORR) kinetics and mass transport. Benefiting from the unique feature, the final obtained material shows an ORR half-wave potential of 0.885 V, higher than that of benchmark Pt/C (0.850 V). When assembled into zinc-air battery, a large peak power density of 208 mW cm-2 is achieved, which is far superior to that of Pt/C (119 mW cm-2). This work provides an economical and feasible strategy to prepare hierarchically porous CN-FeSACs for energy conversion.

Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy.

Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p=0.015). The median follow-up time was 1,240 days (range: 709-1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p=0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft-versus-host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.

[Knockdown of NLRC3 promotes proliferation and invasion of human colon cancer cells].

Objective To investigate the effects of nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 3 (NLRC3) on the proliferation, migration and invasion of human colon cancer HCT116 and LoVo cells. Methods NLRC3 was knocked down in HCT116 and LoVo cells by NLRC3-specific siRNA (si-NLRC3). NLRC3 mRNA and protein expression was detected by real-time quantitative PCR and Western blotting. The proliferation ability of cancer cells was detected by CCK-8 assay; the clone formation ability was detected by clone formation assay; the invasion ability was detected by TranswellTM assay; the migration ability was detected by cell scratch healing assay. Results The transfection of si-NLRC3 down-regulated the expression of NLRC3 in HCT116 and LoVo cells. After NLRC3 knockdown, the proliferation and invasion ability of colon cancer cells were significantly strengthened and the cell migration was not significantly changed. Conclusion Knockdown of NLRC3 in HCT116 and LoVo cells can enhance cell proliferation and invasion ability, but has no effects on cancer cell migration.

Characterizing the partitioning behavior of formaldehyde, benzene and toluene on indoor fabrics: Effects of temperature and humidity.

Fabrics are widely distributed in residential buildings. Due to their highly porous structures and large specific surface areas, they have strong adsorption properties for volatile organic compounds (VOCs). The secondary source effect that is induced by their desorption can aggravate indoor air pollution and prolong the pollution period. The partition coefficient, which is a characteristic parameter of VOC mass transfer, is sensitive to variations in environmental parameters. However, due to the inherent differences between fabrics and other indoor porous building materials, the relevant research conclusions on the VOC mass transfer parameters of building materials cannot be applied. In addition, the effects of temperature and humidity on the partitioning behavior of VOCs on fabrics have rarely been quantitatively analyzed. Based on an analysis of the porous structure and corresponding mass transfer process of fabrics, a novel prediction model of the fabric partition coefficient under the coupling effect of temperature and humidity is proposed. Three types of indoor typical fabrics and primary water-soluble VOC (formaldehyde) and water-insoluble VOC (benzene, toluene) are examined experimentally via hygroscopicity tests and environmental chamber tests. The experimental results demonstrate the reliability of the proposed model for a variety of conditions.

Sorption of tetrabromobisphenol A onto microplastics: Behavior, mechanisms, and the effects of sorbent and environmental factors.

Microplastics (MPs) and halogenated organic pollutants coexist in ambient water and MPs tend to sorb organic pollutants from surrounding environments. Herein, a study on the sorption behavior of tetrabromobisphenol-A (TBBPA) onto four different MPs, namely, polyethylene (PE), polypropylene (PP), polystyrene (PS), and polyvinyl chloride (PVC) was carried out. Effects of MPs properties and environmental factors, including the type, surface charge and pore volume as well as the ionic strength (Ca2+) and humic acid (HA) on the sorption of TBBPA were discussed. Results showed that the sorption of TBBPA onto the MPs could reached an equilibrium within 24 h, and the sorption capacities decreased in the following order -PVC (101.85 mg kg-1) >PS (78.95 mg kg-1) >PP (58.57 mg kg-1) >PE (49.43 mg kg-1). Adsorption kinetics data fitted by intraparticle diffusion model revealed both surface sorption and intraparticle diffusion contributed, in the interfacial diffusion stage approximately 11-29% of TBBPA slowly diffused onto the surface of the MPs, and finally, in the intraparticle diffusion stage. The increase of Ca2+ concentration could promote the sorption of TBBPA by PE, PP, and PS, but no significant alteration for PVC. For all the four MPs, HA was found to exert a negative effect on TBBPA sorption. The adsorption was mainly driven by hydrophobic partition and electrostatic interactions.

Competitive redox reaction of Au-NCs/MnO2 nanocomposite: Toward colorimetric and fluorometric detection of acid phosphatase as an indicator of soil cadmium contamination.

In this study, by rational regulating the competitive redox reaction of Au-NCs/MnO2 nanocomposite between the dye indigo carmine (IC) and the enzymatic product L-ascorbic acid (AA), we have established a colorimetric and fluorometric double-channel responsive assay for acid phosphatase (ACP), which could serve as an indicator of soil cadmium (Cd) contamination. Initially, the gold nanoclusters (Au-NCs) were added to the suspension of MnO2 nanosheets to form Au-NCs/MnO2 nanocomposite with enhanced oxidative degradation ability. When IC was subsequently added, the blue color of IC faded due to oxidative degradation, and the mixture showed the yellow color of Au-NCs/MnO2 nanocomposite. Meanwhile, based on the inner filter effect (IFE), the fluorescence of Au-NCs was suppressed by MnO2 nanosheets during this process. However, with the presence of AA, hydrolyzed from L-ascorbic-2-phosphate (AAP) by ACP, the MnO2 nanosheets in Au-NCs/MnO2 nanocomposite were reduced to Mn2+ immediately. As a consequence, IC remained its blue color, in the meantime, the fluorescence of Au-NCs recovered, which essentially constituted a new mechanism for ACP detection with colorimetric and fluorometric double-channel response. With the method we developed, soil ACP activity can either be directly visualized by bare eyes or detected reliably through double channels. Furthermore, the dynamic changes of ACP activity during soil Cd contamination could also be monitored; the sharp increase of ACP activity at an appropriate time point could serve as a unique alarm for cadmium (Cd) contamination in soil, which is of great importance for soil quality evaluation and ecological risk assessment.

Melt-Processed Poly(Ether Ether Ketone)/Carbon Nanotubes/Montmorillonite Nanocomposites with Enhanced Mechanical and Thermomechanical Properties.

The agglomeration problem of nanofillers, for instance, carbon nanotubes (CNTs) in a poly(ether ether ketone) (PEEK) matrix, is still a challenging assignment due to the intrinsic inert nature of PEEK to organic solvents. In this work, organically modified montmorillonite (MMT) was introduced as a second filler for improving the dispersion of CNTs in the PEEK matrix and enhancing the mechanical properties, as well as reducing the cost of the materials. The nanocomposites were fabricated through melt-mixing PEEK with CNTs/MMT hybrids, which were prepared in advance by mixing CNTs with MMT in water. The introduction of MMT improved the dispersion stability of CNTs, as characterized by sedimentation and zeta potential. The CNTs/MMT hybrids were maintained in PEEK nanocomposites as demonstrated by the transmission electron microscope. The mechanical and thermomechanical measurements revealed that CNTs together with MMT had a strong reinforcement effect on the PEEK matrix, especially at high temperature, although it had a negative effect on the toughness. A maximum increase of 48.1% was achieved in storage modulus of PEEK nanocomposites with 0.5 wt% CNTs and 2 wt% MMT at 240 °C, compared to that of neat PEEK. The differential scanning calorimetry results revealed that CNTs accelerated the crystallization of the PEEK matrix while a further addition of MMT played an opposite role. The nucleation activity of the fillers was also evaluated by the Dobreva method.

Clinical prognostic factors for pediatric extra-abdominal desmoid tumor: analyses of 66 patients at a single institution.

BACKGROUND AND PURPOSE: Pediatric desmoid tumor (PDT) is rare and has a high local recurrence rate. The purpose of the present study was to analyze clinical risk factors of local recurrence in PDT patients. MATERIALS AND METHODS: We reviewed clinical data of 66 PDT patients from 2004 to 2015. All patients underwent macroscopically complete resection, and some recurrent tumors were prescribed radiotherapy. Factors such as sex, age at presentation, location, and proximity to nerves or vasculature were analyzed. The local recurrence rate and recurrence-free survival were analyzed with these factors. RESULTS: All patients in the present study were children and had extra-abdominal tumors. The median follow-up time was 6.6 years. Thirty-six (55%) patients had local recurrence. Age, sex, tumor site, tumor size, and proximity to nerves/vasculature had a significant impact on prognosis in univariate analysis. Radiotherapy decreased the local recurrence rate. In multivariate analysis, younger age, tumor location in buttocks, larger tumor, and proximity to important nerves/vasculature were independent risk factors for poor prognosis. CONCLUSIONS: Favorable therapeutic strategies could be selected according to the preoperative prognostic risk factors. Radiotherapy should be considered for local recurrence of PDT.

Guided bone regeneration using a bone tissue engineering complex consisting of a poly-dl-lactide membrane and bone mesenchymal stem cells.

Developmental dysplasia of the hip (DDH) is one of the most common diseases encountered in pediatric orthopedic departments. Current treatment strategies seek to improve acetabular coverage, the principal defect of acetabular dysplasia, but are not very successful. We developed a guided bone regeneration (GBR) strategy to improve acetabular coverage via bone tissue engineering (BTE). Poly-dl-lactide (PDLLA) membranes were seeded with bone marrow mesenchymal stem cells (BMSCs) to form a BTE complex, which was then implanted into the superior margin of the acetabulum in a rabbit DDH model. Twelve weeks later, a small amount of high-density shadowing was evident on X-rays of the superior margin of the acetabulum, specimens of which exhibited new bone formation. Micro-computed tomography yielding three-dimensional images revealed that new bone had formed in the superior acetabulum, the basal part of which had fused with (and thus reconstructed) the autogenous bone, and new trabecular bone featuring transverse interlacing was evident in the interior of the hip. No clear evidence of bone formation was observed in rabbits that underwent sham operations or that were implanted with PDLLA only. Thus, it may be possible to improve acetabular coverage via BTE-based bone regeneration.

Combined effects of cadmium and tetrabromobisphenol a (TBBPA) on development, antioxidant enzymes activity and thyroid hormones in female rats.

Tetrabromobisphenol A (TBBPA) is one of the world's most widely used brominated flame retardants (BFRs) and considered as persistent halogenated contaminant. E-wastes contain a range of toxic chemicals, including BFRs and heavy metals, exerting adverse impacts to human health and environment. Nevertheless, comprehensive evaluation on combined toxicity of these co-existing pollutants is limited. This study conducted a subchronic effects of cadmium and TBBPA on the development and antioxidative defense system as well as thyroid functions in female rats through single and combined exposure at environmentally relevant doses for a 20-day consecutive administration. Body indexes, histopathology, redox status, and thyroid hormones levels were assessed. Slower body weight gains and reduced ovary weight (20.8% and 32.4% for combined and single-Cd exposures, respectively) were observed with significant variation from controls in high dose treatments. Co-exposure resulted in a slight enhancement in TSH levels compared to control (by 7.6% for high dose) without significance. TBBPA-Cd interactions are involved in the changes of kidney weight as well as the induction of SOD activities and MDA levels. The disturbances in the redox status may be a result of an independent effect of Cd and/or TBBPA and also of their interaction. The results implied under these treatment, kidney was more sensitive with significant increased organ coefficient and alteration for antioxidative indices (increasing by 46% for SOD activity). This study represents the toxic effects of Cd and TBBPA co-exposure through oral administration in pubertal rats, which may provide useful information for health risk assessment for young exposed individuals.

Separation of pygopagus, omphalopagus, and ischiopagus with the aid of three-dimensional models.

BACKGROUND: The three-dimensional (3D) technique provides with accurate anatomical information. We present the separation surgeries for three different kinds of conjoined twins with the aid of three-dimensional techniques. METHOD: For the pygopagus twins, a pelvic and lower vertebral model was made. For the omphalopagus and ischiopagus, their enhanced computed tomography (CT) scan images were transferred to the Computer-Assisted Surgery Planning System (CASP) (Hisense, Qingdao, China) to generate the 3D models. RESULT: In the case of the pygopagus twins, the 3D model clearly showed that their coccyges were joined at a 120°angle from each other horizontally which suggested that the blind-end orifice on their back was a pilonidal sinus, which separated the normal sphincter into two halves. In the omphalopagus, the 3D model revealed one of the branches of each twin's hepatic vein was connected with the other's. The 3D model of the ischiopagus twins revealed that both of the twins had duplicated bladders and each baby's duplicated bladders united with one of the bladders of the other baby and a single rectum passing through the middle of the four bladders. CONCLUSION: 3D techniques could provide more detailed anatomical information, which is helpful in planning procedures for such complicated separation surgery. LEVELS OF EVIDENCE: Level IV.

Construction and immunological characterization of CD40L or GM-CSF incorporated Hantaan virus like particle.

Infection of Hantaan virus (HTNV) usually causes hemorrhagic fever with renal syndrome (HFRS). China has the worst epidemic incidence of HFRS as well as high fatality. Inactivated whole virus has been used for HFRS vaccination, however there are still problems such as safety concerns. CD40 ligand (CD40L) and granulocyte macrophage colony-stimulating factor (GM-CSF) are well-known immune stimulating molecules that can enhance antigen presenting, lymphocytes activation and maturation, incorporation of CD40L and GM-CSF to the surface of virus like particles (VLPs) can greatly improve the vaccination effect. We constructed eukaryotic vectors expressing HTNV M segment and S segment, as well as vectors expressing HTNV M segment with CD40L or GM-CSF, our results showed successful production of CD40L or GM-CSF incorporated HTNV VLPs. In vitro stimulation with CD40L or GM-CSF anchored HTNV VLP showed enhanced activation of macrophages and DCs. CD40L/GM-CSF incorporated VLP can induce higher level of HTNV specific antibody and neutralizing antibody in mice. Immunized mice splenocytes showed higher ability of secreting IFN-γ and IL-2, as well as enhancing CTL activity. These results suggest CD40L/GM-CSF incorporated VLP can serve as prospective vaccine candidate.