Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

Development of antiviral carbon quantum dots that target the Japanese encephalitis virus envelope protein.

Japanese encephalitis is a mosquito-borne disease caused by the Japanese encephalitis virus (JEV) that is prevalent in Asia and the Western Pacific. Currently, there is no effective treatment for Japanese encephalitis. Curcumin (Cur) is a compound extracted from the roots of Curcuma longa, and many studies have reported its antiviral and anti-inflammatory activities. However, the high cytotoxicity and very low solubility of Cur limit its biomedical applications. In this study, Cur carbon quantum dots (Cur-CQDs) were synthesized by mild pyrolysis-induced polymerization and carbonization, leading to higher water solubility and lower cytotoxicity, as well as superior antiviral activity against JEV infection. We found that Cur-CQDs effectively bound to the E protein of JEV, preventing viral entry into the host cells. In addition, after continued treatment of JEV with Cur-CQDs, a mutant strain of JEV was evolved that did not support binding of Cur-CQDs to the JEV envelope. Using transmission electron microscopy, biolayer interferometry, and molecular docking analysis, we revealed that the S123R and K312R mutations in the E protein play a key role in binding Cur-CQDs. The S123 and K312 residues are located in structural domains II and III of the E protein, respectively, and are responsible for binding to receptors on and fusing with the cell membrane. Taken together, our results suggest that the E protein of flaviviruses represents a potential target for the development of CQD-based inhibitors to prevent or treat viral infections.

Description of Photodegradation Mechanisms and Structural Characteristics in Carbon@Titania Yolk-Shell Nanostructures by XAS.

Carbon@titania yolk-shell nanostructures are successfully synthesized at different calcination conditions. These unique structure nanomaterials can be used as a photocatalyst to degrade the emerging water pollutant, acetaminophen (paracetamol). The photodegradation analysis studies have shown that the samples with residual carbon nanospheres have improved the photocatalytic efficiency. The local electronic and atomic structure of the nanostructures are analyzed by X-ray absorption spectroscopy (XAS) measurements. The spectra confirm that the hollow shell has an anatase phase structure, slight lattice distortion, and variation in Ti 3d orbital orientation. In situ XAS measurements reveal that the existence of amorphous carbon nanospheres inside the nano spherical shell inhibit the recombination of electron-hole pairs; more mobile holes are formed in the p-d hybridized bands near the Fermi surface and enables the acceleration of the carries that significantly enhance the photodegradation of paracetamol under UV-visible irradiation. The observed charge transfer process from TiO2  hybridized orbital to the carbon nanospheres reduces the recombination rate of electrons and holes, thus increasing the photocatalytic efficiency.

High Amplification of the Antiviral Activity of Curcumin through Transformation into Carbon Quantum Dots.

It is demonstrated that carbon quantum dots derived from curcumin (Cur-CQDs) through one-step dry heating are effective antiviral agents against enterovirus 71 (EV71). The surface properties of Cur-CQDs, as well as their antiviral activity, are highly dependent on the heating temperature during synthesis. The one-step heating of curcumin at 180 °C preserves many of the moieties of polymeric curcumin on the surfaces of the as-synthesized Cur-CQDs, resulting in superior antiviral characteristics. It is proposed that curcumin undergoes a series of structural changes through dehydration, polymerization, and carbonization to form core-shell CQDs whose surfaces remain a pyrolytic curcumin-like polymer, boosting the antiviral activity. The results reveal that curcumin possesses insignificant inhibitory activity against EV71 infection in RD cells [half-maximal effective concentration (EC50 ) >200 µg mL-1 ] but exhibits high cytotoxicity toward RD cells (half-maximal cytotoxic concentration (CC50 ) <13 µg mL-1 ). The EC50 (0.2 µg mL-1 ) and CC50 (452.2 µg mL-1 ) of Cur-CQDs are >1000-fold lower and >34-fold higher, respectively, than those of curcumin, demonstrating their far superior antiviral capabilities and high biocompatibility. In vivo, intraperitoneal administration of Cur-CQDs significantly decreases mortality and provides protection against virus-induced hind-limb paralysis in new-born mice challenged with a lethal dose of EV71.

Electronic properties of free-standing TiO2 nanotube arrays fabricated by electrochemical anodization.

Nanotubular TiO2 has attracted considerable attention owing to its unique functional properties, including high surface area and vectorial charge transport along the nanotube, making it a good photocatalytic material. Anodic TiO2-nanotube (TiNT) arrays on a Ti foil substrate were prepared by electrochemical anodic oxidation and SEM/HRTEM/XRD analyses have suggested that the walls of TiO2 tubes are formed from stacked [101] planes (anatase). Both HRTEM and XRD indicate an interplanar spacing of d101 = 0.36 nm in the wall structure. Despite the large amount of work done on nanotube synthesis, a thorough investigation of the electronic and atomic structures of free-standing TiNT arrays has not yet been carried out. X-ray absorption spectroscopy (XAS), resonant inelastic X-ray scattering (RIXS) and scanning photoelectron microscopy (SPEM) are employed herein to examine the electronic and atomic structures at the top and bottom of TiNT arrays. These analyses demonstrate the presence of mixed valence states of the Ti ions (Ti(3+) and Ti(4+)) and a structural distortion at the bottom cap region of the TiNT. Additionally, the results obtained herein suggest the formation of a defective anatase phase at the bottom cap barrier layer between the Ti foil substrate and TiNT during the growth of electrochemically anodized nanotubes.

Adsorption isotherms and kinetics of activated carbons produced from coals of different ranks.

Activated carbons (ACs) from six coals, ranging from low-rank lignite brown coal to high-rank stone coal, were utilized as adsorbents to remove basic methylene blue (MB) from an aqueous solution. The surface properties of the obtained ACs were characterized via thermal analysis, N2 isothermal sorption, scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and Boehm titration. As coal rank decreased, an increase in the heterogeneity of the pore structures and abundance of oxygen-containing functional groups increased MB coverage on its surface. The equilibrium data fitted well with the Langmuir model, and adsorption capacity of MB ranged from 51.8 to 344.8 mg g⁻¹. Good correlation coefficients were obtained using the intra-particle diffusion model, indicating that the adsorption of MB onto ACs is diffusion controlled. The values of the effective diffusion coefficient ranged from 0.61 × 10⁻¹° to 7.1 × 10⁻¹° m² s⁻¹, indicating that ACs from lower-rank coals have higher effective diffusivities. Among all the ACs obtained from selected coals, the AC from low-rank lignite brown coal was the most effective in removing MB from an aqueous solution.

Curcumin-derived carbon quantum dots: Dual actions in mitigating tau hyperphosphorylation and amyloid beta aggregation.

The amyloid cascade and tau hypotheses both hold significant implications for the pathogenesis of Alzheimer's disease (AD). Curcumin shows potential by inhibiting the aggregation of amyloid beta (Aß) and reducing tau hyperphosphorylation, however, its use is limited due to issues with solubility and bioavailability. Carbon dots, recognized for their high biocompatibility and optimal water solubility, have demonstrated the capability to inhibit either Aß or tau aggregation. Nonetheless, their effects on tau hyperphosphorylation are yet to be extensively explored. This study aims to evaluate the water-soluble curcumin-derived carbon quantum dots (Cur-CQDs) synthesized via an eco-friendly method, designed to preserve the beneficial effects of curcumin while overcoming solubility challenges. The synthesis of Cur-CQDs involves a single-step dry heating process using curcumin, resulting in dots that exhibit negligible cytotoxicity to SH-SY5Y cells at the examined concentrations. Notably, Cur-CQDs have shown the ability to simultaneously mitigate Aß aggregation and tau hyperphosphorylation. Therefore, it is suggested that Cur-CQDs may hold potential for AD treatment, a hypothesis deserving of further research.

Single-Step Low-Temperature Synthesis of Carbon Dots for Advanced Multiparametric Bioimaging Probe Applications.

Carbon dots (CDs) have recently emerged in biomedical and agricultural domains, mainly for their probe applications in developing efficient sensors. However, the existing high-temperature approaches limit the industrial level scaling up to further translate them into different products by mass-scale fabrication of CDs. To address this, we have attempted to lower the synthesis temperature to 140 °C and synthesized different CDs using different organic acids and their combinations in a one-step approach (quantum yield 3.6% to 16.5%; average size 3 to 5 nm). Further, sensing applications of CDs have been explored in three different biological models, mainly Danio rerio (zebrafish) embryos, bacterial strains, and the Lactuca sativa (lettuce) plant. The 72 h exposure of D. rerio embryos to 0.5 and 1 mg/mL concentrations of CDs exhibited significant uptake without mortality, a 100% hatching rate, and nonsignificant alterations in heart rate. Bacterial bioimaging experiments revealed CD compatibility with Gram-positive (Bacillus subtilis) and Gram-negative (Serratia marcescens) strains without bactericidal effects. Furthermore, CDs demonstrated effective conduction and fluorescence within the vascular system of lettuce plants, indicating their potential as in vivo probes for plant tissues. The single-step low-temperature CD synthesis approach with efficient structural and optical properties enables the process as industrially viable to up-scale the technology readiness level. The bioimaging of CDs in different biological models indicates the possibility of developing a CD probe for diverse biosensing roles in diseases, metabolism, microbial contamination sensing, and more.

Dual-emissive carbonized polymer dots for the ratiometric fluorescence imaging of singlet oxygen in living cells.

Singlet oxygen (1O2) is a type of reactive oxygen species (ROS), playing a vital role in the physiological and pathophysiological processes. Specific probes for monitoring intracellular 1O2 still remain challenging. In this study, we develop a ratiometric fluorescent probe for the real-time intracellular detection of 1O2 using o-phenylenediamine-derived carbonized polymer dots (o-PD CPDs). The o-PD CPDs possessing dual-excitation-emission properties (blue and yellow fluorescence) were successfully synthesized in a two-phase system (water/acetonitrile) using an ionic liquid tetrabutylammonium hexafluorophosphate as a supporting electrolyte through the electrolysis of o-PD. The o-PD CPDs can act as a photosensitizer to produce 1O2 upon white LED irradiation, in turn, the generated 1O2 selectively quenches the yellow emission of the o-PD CPDs. This quenching behavior is ascribed to the specific cycloaddition reaction between 1O2 and alkene groups in the polymer scaffolds on o-PD CPDs. The interior carbon core can be a reliable internal standard since its blue fluorescence intensity remains unchanged in the presence of 1O2. The ratiometric response of o-PD CPDs is selective toward 1O2 against other ROS species. The developed o-PD CPDs have been successfully applied to monitor the 1O2 level in the intracellular environment. Furthermore, in the inflammatory neutrophil cell model, o-PD CPDs can also detect the 1O2 and other ROS species such as hypochlorous acid after phorbol 12-myristate 13-acetate (PMA)-induced inflammation. Through the dual-channel fluorescence imaging, the ratiometric response of o-PD CPDs shows great potential for detecting endogenous and stimulating 1O2in vivo.

Impact of subjective sleep quality on glycemic control in type 2 diabetes mellitus.

BACKGROUND: Glycaemic control is fundamental to the management of and risk reduction in microvascular complications of diabetes. OBJECTIVES: The aim of this study was to investigate the association of sleep quality with glycaemic control and its impact on type 2 diabetic patients in an Asian population. METHODS: A total of 46 subjects with type 2 diabetes mellitus were enrolled. HbA1C was measured in each patient, and each patient completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Good sleep quality was defined as PSQI score ≤5. RESULTS: After adjusting for age, gender and body mass index, the total PSQI score and sleep efficiency (P < 0.05) were significantly correlated with the level of HbA1C. Logistic regression analysis showed the adjusted odds ratio (OR) of sleep efficiency for HbA1C level was 6.83 [OR = 6.83, 95% confidence interval (CI) = 2.04-22.8, P = 0.002]. The adjusted ORs of worse glycaemic control for the poor sleep quality group was 6.94 with regard to the group of good sleep quality (OR = 6.94, 95% CI: 1.02-47.16, P < 0.05). CONCLUSIONS: This study demonstrated that both poor sleep quality and less-efficient sleep are significantly correlated with worse glycaemic control in patients with type 2 diabetes. These findings are expected to contribute to the prevention and risk reduction of microvascular complications in type 2 diabetes.

Photodegradation of aqueous reactive dye using TiO(2)/zeolite admixtures in a continuous flow reactor.

The photocatalytic degradation of an organic dye, i.e. reactive blue 19 (RB19), was studied by employing different TiO(2)/zeolite (TZ) photocatalysts, which have TiO(2)/(TiO(2) + zeolite) weight ratios ranging from 20 to 80%, in a continuous flow system. Three light sources including two UV lights (i.e. λ(max,254 nm) and λ(max,365 nm)) and natural sunlight were used. The results showed that the decoloring rate of RB19 increased as the amount of TiO(2) in the TZ catalyst increased. The photodegradation of RB19 exhibited pseudo-first-order kinetics with respect to the concentration of RB19. Almost 100% of initial RB19 was mineralized under the controlled conditions in this study. And the activities of the prepared photocatalysts were retained after long-term durability experiments. Compared with UV lights (i.e. λ(max,254 nm) and λ(max,365 nm)), the decoloring efficiency of RB19 was significantly increased under natural sunlight illumination, which is likely due to the long-wavelength incident light that photoexcited RB19 and accelerated the degradation rate of RB19 radicals by the UV fraction of sunlight.

Titania spheres with nanochannel-restricted NaNO2/MgO for improving cyclic CO2 adsorption stability.

NaNO2/MgO/titania spheres prepared via aerosol-assisted self-assembly (AASA) were used as sorbents for CO2 adsorption at moderate temperature. The titania framework as support would allow MgO to disperse well, thereby increasing the contact between MgO and NaNO2 to enhance carbonation. In this study, the effect of Mg/Ti molar ratio and NaNO2 addition amount on CO2 adsorption was investigated. Results showed that the sorbent prepared by AASA with Mg/Ti molar ratio of 2 following the introduction of 30 wt% NaNO2 presented ∼1 µm particle size with rough sphere surface morphology and mesoporous properties, where the surface area and pore volume were 72 m2/g and 0.18 cm3/g, respectively. With NaNO2 addition, the kinetics and capacity of CO2 adsorption significant increased. In the cyclic adsorption/desorption experiment, the superior stability over the NaNO2/MgO/titania spheres was mainly ascribed to the confined space suppressed the degree of the sintering effect. These results indicated the potential application of the nanochannel-restricted sorbent for rapid, high-capacity, and stable CO2 capture at moderate temperatures.

Carbon-based low-pressure filtration membrane for the dynamic disruption of bacteria from contaminated water.

Carbon-based materials, especially graphene oxide (GO) and carbon dots possessing antibacterial properties, are widely used for various applications. Recently, we reported the antibacterial and antioxidant properties of carbonized nanogels (CNGs) for the treatment of bacterial keratitis, and as a virostatic agent against infectious bronchitis virus. In this work, we demonstrate the use of CNGs/GO nanocomposite (GO@CNGs) membrane for the efficient removal of Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria from contaminated water. The GO@CNGs composite membrane with an optimized ratio of GO to CNGs could achieve more than 99% removal efficiency toward E. coli and S. aureus. Various strains of bacteria interact differently with the membrane, and hence the membrane shows different removal rate, which can be optimized by controlling the interaction time through regulating the water flux. The GO@CNGs membrane with an active area of 2.83 cm2 achieved > 99% bacterial removal efficiency at a water flux of 400 mL min-1 m-2. The dynamic disruption of bacteria by GO@CNGs plays a crucial role in eliminating the bacteria. Rather than filtering out the bacteria, GO@CNGs membrane allows them to pass through it, interact with the bacteria and rupture the bacterial cell membranes. Our GO@CNGs membrane shows great potential as a filter to remove bacteria from contaminated water samples, operating under tap water pressure without any extra power consumption.

Partial carbonization of quercetin boosts the antiviral activity against H1N1 influenza A virus.

Inflenza A viruses (IAVs) are highly transmissible and pathogenic Orthomyxoviruses, which have led to worldwide outbreaks and seasonal pandemics of acute respiratory diseases, causing serious threats to public health. Currently used anti-influenza drugs may cause neurological side effects, and they are increasingly less effective against mutant strains. To help prevent the spread of IAVs, in this work, we have developed quercetin-derived carbonized nanogels (CNGsQur) that display potent viral inhibitory, antioxidative, and anti-inflammatory activities. The antiviral CNGsQur were synthesized by mild carbonization of quercetin (Qur), which successfully preserved their antioxidative and anti-inflammatory properties while also contributed enhanced properties, such as water solubility, viral binding, and biocompatibility. Antiviral assays of co-treatment, pre-treatment, and post-treatment indicate that CNGsQur interacts with the virion, revealing that the major antiviral mechanism resulting in the inhibition of the virus is by their attachment on the cell surface. Among them, the selectivity index (SI) of CNGsQur270 (>857.1) clearly indicated its great potential for clinical application in IAVs inhibition, which was much higher than that of pristine quercetin (63.7) and other clinical drugs (4-81). Compared with quercetin at the same dose, the combined effects of viral inhibition, antioxidative and anti-inflammatory activities impart the superior therapeutic effects of CNGsQur270 aerosol inhalation in the treatment of IAVs infection, as evidenced by a mouse model. These CNGsQur effectively prevent the spread of IAVs and suppress virus-induced inflammation while also exhibiting good in vivo biocompatibility. CNGsQur shows much promise as a clinical therapeutic agent against infection by IVAs.

Aminoglycoside-mimicking carbonized polymer dots for bacteremia treatment.

Bacteremia and associated bacterial sepsis are potentially fatal and occur when the host response to microbial invasion is impaired or compromised. This motivated us to develop carbonized polymer dots (CPDsMan/AA) from a mixture of mannose (Man) and positively charged amino acids [AAs; lysine, arginine (Arg), or histidine] through a one-step mild pyrolysis procedure, which effectively inhibited drug-resistant bacterial strains isolated from septic patients. The as-prepared CPDsMan/AA showed broad-spectrum antibacterial activity, including multidrug-resistant bacteria, even in human plasma. The minimal inhibitory concentration of CPDsMan/Arg is ca. 1.0 µg mL-1, which is comparable to or lower than those of other tested antibiotics (e.g., ampicillin, gentamicin, and vancomycin). In addition to directly disrupting bacterial membranes, the CPDsMan/Arg feature a structure similar to aminoglycoside antibiotics that could bind to 16S rRNA, thereby blocking bacterial protein synthesis. In vitro cytotoxic and hemolytic assays demonstrated the high biocompatibility of the CPDsMan/AA. In addition, in vivo studies on methicillin-resistant Staphylococcus aureus-infected mice treated with the CPDsMan/Arg showed a significant decrease in mortality-even better than that of antibiotics. Overall, the synthesis of the CPDsMan/AA is cost-efficient, straightforward, and effective for treating bacteremia. The polymeric features of the CPDsMan/Arg, including cationic charges and specific groups, can be recognized as a safe and broad-spectrum biocide to lessen our reliance on antibiotics to treat systemic bacterial infections in the future.

Multicycle Performance of CaTiO3 Decorated CaO-Based CO2 Adsorbent Prepared by a Versatile Aerosol Assisted Self-Assembly Method.

Calcium oxide (CaO) is a promising adsorbent to separate CO2 from flue gas. However, with cycling of carbonation/decarbonation at high temperature, the serious sintering problem causes its capture capacity to decrease dramatically. A CaTiO3-decorated CaO-based CO2 adsorbent was prepared by a continuous and simple aerosol-assisted self-assembly process in this work. Results indicated that CaTiO3 and CaO formed in the adsorbent, whereas CaO gradually showed a good crystalline structure with increased calcium loading. Owing to the high thermal stability of CaTiO3, it played a role in suppressing the sintering effect and maintaining repeated high-temperature carbonation and decarbonation processes. When the calcium and titanium ratio was 3, the CO2 capture capacity was as large as 7 mmol/g with fast kinetics. After 20 cycles under mild regeneration conditions (700 °C, N2), the performance of CO2 capture of CaTiO3-decorated CaO-based adsorbent nearly unchanged. Even after 10 cycles under severe regeneration conditions (920 °C, CO2), the performance of CO2 capture still remained nearly 70% compared to the first cycle. The addition of CaTiO3 induced good and firm CaO dispersion on its surface. Excellent kinetics and stability were evident.

Smoking Cessation Rate and Its Predictors among Heavy Smokers in a Smoking-Free Hospital in Taiwan.

Smoking poses critical risks for heart disease and cancers. Heavy smokers, defined as smoking more than 30 pack-year, are the most important target for smoking cessation. This study aimed to obtain the cessation rate and its predictors among heavy smokers. We collected data from heavy smokers who visited a smoking-free hospital in Taiwan during 2017. All patients were prescribed either varenicline or nicotine replacement therapy (NRT) for smoking cessation, and their smoking status was followed for six months. Successful smoking cessation was defined by self-reported no smoking over the preceding seven days (7-day point abstinence). In total, 280 participants with a mean aged of 53.5 years were enrolled, and 42.9% of participants successfully stopped smoking in 6 months. The results revealed that quitters were older, with hypertension, fewer daily cigarettes, and being prescribed with varenicline. Multiple logistic regressions analyses identified that fewer daily cigarettes and being prescribed with varenicline were predictors of successful smoking cessation. Therefore, we suggest that varenicline use may help heavy smokers in smoking cessation.

High-performance and long-term stability of mesoporous Cu-doped TiO2 microsphere for catalytic CO oxidation.

Although the low-temperature reaction mechanism of catalytic CO oxidation reaction remains unclear, the active sites of copper play a crucial role in this mechanism. One-step aerosol-assisted self-assembly (AASA) process has been developed for the synthesis of mesoporous Cu-doped TiO2 microspheres (CuTMS) to incorporate copper into the TiO2 lattice. This strategy highly enhanced the dispersion of copper from 41.10 to 83.65%. Long-term stability of the as-synthesized CuTMS materials for catalytic CO oxidation reaction was monitored using real-time mass spectrum. Isolated CuO and Cu-O-Ti were formed as determined by X-ray photoelectron spectroscopy (XPS). The formation of the Cu-O-Ti bonds in the crystal lattice changes the electron densities of Ti(IV) and O, causing a subsequent change in Ti(III)/Ti(IV) and Onon/OTotal ratio. 20CuTMS contained the highest lattice distortion (0.44) in which the Onon/OTotal ratio is lowest (0.18). This finding may be attributed to the absolute formation of the Cu-O-Ti bonds in the crystal lattice. However, the decrease of Ti(III)/Ti(IV) ratio to about 0.35 of 25CuTMS was caused by the CuO cluster formation on the surface. N2O titration-assisted H2 temperature-programmed reduction and in-situ Fourier transform infrared spectroscopy revealed the properties of copper and effects of active sites.

Hyaluronic Acid Derived Hypoxia-Sensitive Nanocarrier for Tumor Targeted Drug Delivery.

Hyaluronic acid (HA) is conjugated with BHQ3 moiety with azo bonds to prepare hypoxia-responsive polymer conjugate. Because of the amphiphilic nature, the polymer conjugate self-assembles to HA-BHQ3 nanoparticles (NPs). The anticancer drug doxorubicin (DOX) is loaded into the NPs. In the physiological environment, DOX is released slowly. In contrast, under hypoxic conditions, the azo bond in BHQ3 is cleaved, thus significantly enhancing the DOX release rate. For instance, after 24 h, 25% of DOX is released under normal conditions, while 74% of DOX is released under hypoxic conditions. In vitro cytotoxicity demonstrates higher toxicity in the hypoxic conditions. DOX@HA-BHQ3 NPs exhibit greater toxicity levels against 4T1 cells in hypoxic conditions. The fluorescent microscope images confirm the oxygen-dependent intracellular DOX release from the NPs. The in vivo biodistribution results suggest the tumor targetability of HA-BHQ3 NPs in 4T1 tumor-bearing mice.

Small cell lung cancer presenting as ectopic ACTH syndrome with hypothyroidism and hypogonadism.

BACKGROUND: Small-cell lung cancer accounts for 15-20% of all lung cancers, and it is the cell type most commonly associated with paraneoplastic syndrome. Small-cell lung cancer presenting as ectopic adrenocorticotropic hormone (ACTH) syndrome associated with hypothyroidism and hypogonadotropic hypogonadism is clinically very rare. CASE REPORT: A 43-year-old man who presented with bilateral lower-extremity edema and hypokalemia had a mass lesion in his left hilum base visible on chest radiograph. Biopsy identified the mass as small-cell lung cancer with focal ACTH staining. The endocrine tests disclosed hypercortisolism, hypogonadism and hypothyroidism. RESULTS: Partial remission as evidenced by regression of the tumor mass and return to normal serum cortisol and ACTH levels occurred after the first course of combination chemotherapy using cisplatin and etoposide. An unexpected left-sided spontaneous pneumothorax developed after the first course of chemotherapy and was treated with thoracostomy and a chest tube. The patient developed persistent air leakage and chronic empyema. The patient received surgery of the Eloesser flap and reconstruction with the latissimus dorsalis flap. The treatment of the complicated problems was successful. CONCLUSION: Combination chemotherapy may prove effective in the treatment of small-cell lung cancer with ectopic ACTH syndrome, hypothyroidism and hypogonadism.