Controlling graphene ultrafast hot carrier response from metal-like to semiconductor-like by electrostatic gating.

We investigate the ultrafast terahertz response of electrostatically gated graphene upon optical excitation. We observe that the photoinduced terahertz absorption increases in charge neutral graphene but decreases in highly doped graphene. We show that this transition from semiconductor-like to metal-like response is unique for zero bandgap materials such as graphene. In charge neutral graphene photoexcited hot carriers effectively increase electron and hole densities and increase the conductivity. In highly doped graphene, however, photoexcitation does not change net conducting carrier concentration. Instead, it mainly increases electron scattering rate and reduce the conductivity.

Clinical significance of lncRNA-AWPPH in coronary artery diseases.

OBJECTIVE: The aim of this study was to determine serum level of long non-coding RNA (lncRNA)-AWPPH in coronary artery disease (CAD) patients and its clinical significance as a serum marker. PATIENTS AND METHODS: Serum levels of lncRNA-AWPPH in 132 CAD patients and 50 controls were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Based on medical history of statin therapy, differential expressions of lncRNA-AWPPH in CAD patients were examined. Then, the correlation between lncRNA-AWPPH level and clinical data of CAD patients was analyzed. Moreover, risk factors influencing prognosis of CAD were assessed by multivariate logistic regression analysis. RESULTS: It was found that lncRNA-AWPPH was highly expressed in serum of CAD patients, especially those receiving rosuvastatin therapy. LDL-C, hs-CRP, and serum lncRNA-AWPPH were independent risk factors for CAD, while HDL-C was favorable to CAD. CONCLUSIONS: LncRNA-AWPPH is highly expressed in serum of CAD patients, which can be reduced by statin therapy, and it may be a potential serum marker for predicting the prognosis of CAD.

The antiviral mechanisms, effects, safety and adverse effects of chloroquine.

Chloroquine, a 4-aminoquinoline derivative, was initially used to treat malaria. It was later found to have immunomodulating, anti-infective, anti-thrombotic, anti-tumor, and metabolic effects. Recently, many studies have focused on the application of chloroquine in viral infections. Most in vitro studies suggested that chloroquine exerted some benefit in infections from viruses. However, animal experiment and clinical trials that attempted to use chloroquine in prevention or treatment of viral infections have reported disappointing results. It might be attributable to inadequate steady-state whole blood chloroquine concentration necessary for exerting its antiviral effects. A 16 µM/L steady-state whole blood concentration of chloroquine should suffice in antiviral treatment with minimal toxicity. Furthermore, chloroquine has both acute and cumulative toxicity. Hence, not only the appropriate treatment dose is crucial, the occurrence of adverse reactions should also be closely monitored and treated in time. Herein, we report the antiviral mechanisms, effects, safety and adverse effects of chloroquine.

The cohesion protein MEI-S332 localizes to condensed meiotic and mitotic centromeres until sister chromatids separate.

The Drosophila MEI-S332 protein has been shown to be required for the maintenance of sister-chromatid cohesion in male and female meiosis. The protein localizes to the centromeres during male meiosis when the sister chromatids are attached, and it is no longer detectable after they separate. Drosophila melanogaster male meiosis is atypical in several respects, making it important to define MEI-S332 behavior during female meiosis, which better typifies meiosis in eukaryotes. We find that MEI-S332 localizes to the centromeres of prometaphase I chromosomes in oocytes, remaining there until it is delocalized at anaphase II. By using oocytes we were able to obtain sufficient material to investigate the fate of MEI-S332 after the metaphase II-anaphase II transition. The levels of MEI-S332 protein are unchanged after the completion of meiosis, even when translation is blocked, suggesting that the protein dissociates from the centromeres but is not degraded at the onset of anaphase II. Unexpectedly, MEI-S332 is present during embryogenesis, localizes onto the centromeres of mitotic chromosomes, and is delocalized from anaphase chromosomes. Thus, MEI-S332 associates with the centromeres of both meiotic and mitotic chromosomes and dissociates from them at anaphase.

Retraction Note: Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model.

This article has been retracted at the request of the authors. After publication, the authors found that in Figure 2B-a the first two images in the third row partly overlapped and that there is also overlap between the fourth and fifth image in the second row. The two images were taken from two adjacent wells, treated by ZA 0.3uM-CM or ZA 0.75uM-CM, with or without PL 1.25uM. This overlap may have been caused by mishandling in the imaging process when the authors made microscope observations and so the findings are no longer reliable. All authors agree to this retraction.

Biocompatibility and membrane strength of C3H10T1/2 cell-loaded alginate-based microcapsules.

BACKGROUND: C3H10T1/2 cells, from a mouse embryonic fibroblast cell line, were used to investigate the improvement of alginate-based microencapsulated cells for cellular therapy. METHODS: Purified sodium alginate (PSA) and non-purified sodium alginate (SA) were used to prepare alginate-based microcapsules, and their biocompatibility and membrane strength were then compared for the purposes of analyzing the advantages of purifying SA. In addition, poly-l-lysine (PLL) was replaced by chitosan for alginate-chitosan microcapsule preparation. The process of optimization and chemical modification of alginate-chitosan microcapsules using polyethylene glycol was also reviewed. RESULTS: The results showed improved biocompatibility and membrane strength of PSA-based microcapsules. Under optimal conditions, mesenchymal stromal cell (MSC)-loaded alginate-chitosan microcapsules with good morphology could be obtained using PSA and chitosans of medium molecular weight (1.0-2.5 x 10(5)). A chitosan solution of 0.1% (w/v) and a reaction time of 7 min between alginate and chitosan were determined as optimal preparation parameters. DISCUSSION: It could be concluded that the chemical modification of alginate-based microcapsules can improve their biocompatibility.

Surface-enrichment with hydroxyapatite nanoparticles in stereolithography-fabricated composite polymer scaffolds promotes bone repair.

Fabrication of composite scaffolds using stereolithography (SLA) for bone tissue engineering has shown great promises. However, in order to trigger effective bone formation and implant integration, exogenous growth factors are commonly combined to scaffold materials. In this study, we fabricated biodegradable composite scaffolds using SLA and endowed them with osteopromotive properties in the absence of biologics. First we prepared photo-crosslinkable poly(trimethylene carbonate) (PTMC) resins containing 20 and 40wt% of hydroxyapatite (HA) nanoparticles and fabricated scaffolds with controlled macro-architecture. Then, we conducted experiments to investigate how the incorporation of HA in photo-crosslinked PTMC matrices improved human bone marrow stem cells osteogenic differentiation in vitro and kinetic of bone healing in vivo. We observed that bone regeneration was significantly improved using composite scaffolds containing as low as 20wt% of HA, along with difference in terms of osteogenesis and degree of implant osseointegration. Further investigations revealed that SLA process was responsible for the formation of a rich microscale layer of HA corralling scaffolds. To summarize, this work is of substantial importance as it shows how the fabrication of hierarchical biomaterials via surface-enrichment of functional HA nanoparticles in composite polymer stereolithographic structures could impact in vitro and in vivo osteogenesis. STATEMENT OF SIGNIFICANCE: This study reports for the first time the enhance osteopromotion of composite biomaterials, with controlled macro-architecture and microscale distribution of hydroxyapatite particles, manufactured by stereolithography. In this process, the hydroxyapatite particles are not only embedded into an erodible polymer matrix, as reported so far in the literature, but concentrated at the surface of the structures. This leads to robust in vivo bone formation at low concentration of hydroxyapatite. The reported 3D self-corralling composite architecture provides significant opportunities to develop functional biomaterials for bone repair and tissue engineering.

Double-edged-sword effect of IL-1ß on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-κB, MAPK and BMP/Smad signaling pathways.

Microenvironmental conditions can interfere with the functional role and differentiation of mesenchymal stem cells (MSCs). Recent studies suggest that an inflammatory microenvironment can significantly impact the osteogenic potential of periodontal ligament stem cells (PDLSCs), but the precise effects and mechanisms involved remain unclear. Here, we show for the first time that interleukin-1ß (IL-1ß) has dual roles in the osteogenesis of PDLSCs at concentrations ranging from physiologically healthy levels to those found in chronic periodontitis. Low doses of IL-1ß activate the BMP/Smad signaling pathway to promote the osteogenesis of PDLSCs, but higher doses of IL-1ß inhibit BMP/Smad signaling through the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, inhibiting osteogenesis. These results demonstrate that crosstalk between NF-κB, MAPK and BMP/Smad signaling mediates this dual effect of IL-1ß on PDLSCs. We also show that the impaired osteogenesis of PDLSCs results in more inflammatory cytokines and chemokines being released, inducing the chemotaxis of macrophages, which further clarifies the role of PDLSCs in the pathogenesis of periodontitis.

Methylprednisolone combined with low-dose indomethacin treating acute fibrinous and organizing pneumonia after a surgical resection of rectal adenocarcinoma: a case report and literature review.

OBJECTIVE: Acute Fibrinous and Organizing Pneumonia (AFOP) is a new pathologic pattern of acute lung injury characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" in a patchy distribution. CASE REPORT: A 65-years-old female after a surgical resection of rectal adenocarcinoma presented with typical manifestations of hospital-acquired pneumonia, but she didn't respond to the anti infective therapy. After an explicit diagnosis of AFOP via percutaneous needle lung biopsy, she got an impressive improvement with a long-term therapy of methylprednisolone and low-dose indomethacin. To date, a total of non-overlapped 45 individual AFOP cases and 4 single-center studies involving AFOP have been reported. The most common coexisting diseases are infections, connective tissue diseases and hematological diseases. Corticosteroids and immunosuppressants are the most common agents prescribed in AFOP. The prognosis of AFOP is unfavorable, associated with the pathologic characteristics and the clinical parameters. CONCLUSIONS: The immune system activated by infection may play an important role in the pathogenesis of AFOP. Low-dose indomethacin combined with methylprednisolone may be a new choice for AFOP treatment.

Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model.

The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of NF-κB/MAPK (nuclear factor-κB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c-Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk).

Hypereosinophilic obliterative bronchiolitis with an elevated level of serum CEA: a case report and a review of the literature.

A 44-year-old man presented with chronic, persistent cough and occasional wheezing. Airflow obstruction, blood eosinophilia and a remarkable elevated level of serum carcinoembryonic antigen (CEA) were found. Radiographic and pathological studies confirmed eosinophilic bronchiolitis. There was no evidence of neoplasms by extensive examinations. After a protracted oral steroid therapy, the blood eosinophil count, the serum CEA level and the lung lesions were all improved in parallel, whereas fixed airflow obstruction remained. This case was diagnosed as a new distinct syndrome, hypereosinophilic obliterative bronchiolits. Serum CEA and blood eosinophil cell count served as good markers of the disease condition for this syndrome.

Fatal rhabdomyolysis following influenza infection in a girl with familial carnitine palmityl transferase deficiency.

Severe rhabdomyolysis following an influenza B infection developed in a previously well 13-year-old girl. There was no history of trauma. Her course was complicated by episodes of severe hyperkalemia, hypocalcemia, hyperphosphatemia, and myoglobinuria. Renal failure, hypertension, and life-threatening arrhythmias developed; she died. Muscle biopsy revealed that this girl had carnitine palmityl transferase deficiency. An asymptomatic sister was demonstrated to have the same disorder. Although carnitine palmityl transferase deficiency is usually associated with mild bouts of rhabdomyolysis that become apparent only in adulthood, severe forms of this disorder may be seen in children. Life-threatening rhabdomyolysis and myoglobinuria may follow any infection associated with decreased intake. If carnitine palmityl transferase deficiency is diagnosed in a proband, other siblings should be evaluated so that proper preventative measures can be undertaken to help prevent the development of symptoms in susceptible individuals who have not been recognized to have the disease.

Cor pulmonale as a complication of methylmalonic acidemia and homocystinuria (Cbl-C type).

We report an infant with a bronchiolitis-like illness and rapid deterioration who developed a cor pulmonale-like picture with a dilated right ventricle. Urinary organic acid assays established a probable diagnosis of Cbl-C-type methylmalonic aciduria, later confirmed by complementation studies. Despite medical intervention and cyanocobalamin treatment the patient died on his tenth hospital day. Postmortem examination showed the presence of thromboemboli in the pulmonary circulation. We hypothesize that acute cor pulmonale developed in this infant secondary to thromboembolism of his pulmonary circulation. A review of the literature shows that thromboembolism may be a part of this disease process.

Limb body-wall complex in association with sirenomelia sequence.

Limb body-wall complex and sirenomelia sequence are uncommon birth defects and their association is extremely rare. Their overlapping manifestations and their concurrence in our patient suggest that they share a common cause and belong to a group of pathologically closely related conditions. Embryonic vascular disruption may be a common pathogenesis in both anomalies.

Ulcerative eosinophilic granuloma of the tongue. A light- and electron-microscopic study.

Ulcerative eosinophilic granuloma of the tongue simulates histiocytosis X or cancerous lesions, and may be subjected to unnecessary excessive treatment. This case report illustrates its benign, self-limited nature, discussed the differential diagnosis, and postulates its pathogenesis on the basis of light- and electron-microscopic findings.

Cerebral toxoplasmosis in an immunocompromised host. A precise and rapid diagnosis by electron microscopy.

In immunocompromised patients with cerebral toxoplasmosis, the tachyzoite forms rather than cystic and bradyzoite forms of the protozoon are commonly seen. These tachyzoites are minute, scattered among cellular debris, sometimes lodged inside macrophages and neutrophils, and difficult to visualize by light microscopy, even with special stains. Immunodiagnostic tests may be falsely negative due to inability of the host to produce appropriate antibodies. Isolation of the organism is dangerous because Toxoplasma gondii is highly infective. In this situation, transmission electron microscopy (EM) may be a diagnostic tool of choice. It demonstrates the fine definitive features of the protozoon and can be expedited to give results in five hours. Further evaluation of EM for diagnosing possible toxoplasmosis in immunocompromised patients is indicated.

Cerebral blastomycosis: an immunodiagnostic study.

Cerebral blastomycosis may simulate a brain tumor. Its diagnosis is sometimes very difficult. The morphologic identification of the fungus may be misleading because it shares some common features with many other dimorphic fungi. Culturing and conversion of the organism from mycelial phase to yeast phase are not always successful. Immunofluorescent staining of the biopsy tissue is useful in confirming the diagnosis. However, a combination of double immunodiffusion (DID) test and complement fixation (CF) test makes the diagnosis more accurate and reliable. The direct role of macrophages in defending the host against blastomycosis is illustrated by electron microscopy.

Neonatal cystic choristoma in submandibular salivary gland simulating cystic hygroma.

A congenital cystic malformation occurred in the submandibular salivary gland of a neonate. The embryogenesis and differential diagnosis are discussed. Since it seems to be a product of endodermal heterotopic differentiation or entrapment of foregut epithelial rests in the submandibular gland, it is classified as a cystic choristoma.

Leukocyte tubuloreticular inclusions in Reye's syndrome.

Tubuloreticular inclusions (TRI) have been observed in the rough endoplasmic reticulum of blood lymphocytes and monocytes in two cases of Reye's syndrome initiated by influenza infections. Tubuloreticular inclusions are seen in these mononuclear leukocytes during the acute phase of illness, but not during convalescence. Since TRI have been demonstrated in peripheral mononuclear leukocytes in patients with acquired immunodeficiency syndrome, systemic lupus erythematosus, and certain viral infections including T-cell leukemia, it may be that the finding of TRI in Reye's syndrome reflects a viral infection and/or immune dysfunction, if such association is not proved to be fortuitous.