Core-shell ZnO@CoO nitrogen doped nano-composites as highly sensitive electrochemical sensor for organophosphate pesticides detection.

Core-shell ZIF-8@ZIF-67 was synthesized by growing a cobalt-based ZIF-67 on a ZIF-8 seed particle. Herein, through selective etching of the ZIF-8@ZIF-67 core and subsequent direct carbonization, core-shell hollow ZnO@CoO nitrogen-doped nanoporous carbon (HZnO@CoO-NPC) nanocomposites were prepared. HZnO@CoO-NPCs possessed a high nitrogen content, large surface area, high degree of graphitization and excellent electrical conductivity, all of which were attributed to successfully integrating the unique advantages of ZIF-8 and ZIF-67. HZnO@CoO-NPCs were used to assemble acetylcholinesterase (AChE) biosensors for organophosphorus pesticides (OPs) detection. The low detection limit of 2.74 × 10-13 M for chlorpyrifos and 7.6 × 10-15 M for parathion-methyl demonstrated the superior sensing performance. The results showed that the electrochemical biosensor constructed by HZnO@CoO-NPC provided a sensitive and efficient electrochemical strategy for OPs detection.

Performance of T2 mapping in the staging of Graves' ophthalmopathy based on different region of interest selection methods.

BACKGROUND: Discriminating the stage of Graves' ophthalmopathy (GO) is crucial for clinical decision. Application of conventional T2-weighted imaging in the staging is still limited. PURPOSE: To evaluate the performance of T2 mapping based on two different regions of interest (ROIs) for staging GO. MATERIAL AND METHODS: In total, 56 GO patients were retrospectively enrolled and divided into two groups according to the clinical activity score (CAS). T2 relaxation time (T2RT) of extraocular muscle (EOM) on T2 mapping based on two different ROIs (T2RTROI-1: ROIs were drawn separately in the four EOMs; T2RTROI-2: ROI was drawn in the most inflamed EOM) was measured and compared between active and inactive groups. RESULTS: Both T2RTROI-1 and T2RTROI-2 values in the active GO were significantly higher than those of inactive GO (P <0.001). T2RTROI-1 and T2RTROI-2 values were positively correlated with CAS (rs=0.73, 0.69; P <0.001). When the T2RTROI-1 value of 83.3 ms and T2RTROI-2 value of 106.3 ms were used as cutoff values for staging GO, respectively, the best results were obtained with areas under the curve (AUCs) of 0.822 and 0.827. There was no significant difference for AUCs between T2RTROI-1 and T2RTROI-2 (P = 0.751). Excellent and good inter-observer agreements were achieved in quantitative measurements for T2RTROI-1 and T2RTROI-2 values, respectively, with intraclass correlation coefficients of 0.954 and 0.882. CONCLUSION: The T2RT values derived from two different ROIs were useful for assessment of disease activity. Taking reproducibility and diagnostic performance into consideration, T2RTROI-1 would be an ideal image biomarker for staging GO compared to T2RTROI-2.

A flexible semiconductor SERS substrate by in situ growth of tightly aligned TiO2 for in situ detection of antibiotic residues.

Semiconductor materials have become a competitive candidate for surface-enhanced Raman scattering (SERS) substrate. However, powdered semiconductors are difficult to execute a fast in situ detection for trace analytes. Here, we developed a new flexible semiconductor SERS substrate by in situ densely growing anatase TiO2 nanoparticles on the surface of cotton fabric through a filtration-hydrothermal method, in which TiO2 exhibits excellent controllability in size and distribution by regulating the ratio of water to alcohol in synthesis and the number of filtration-hydrothermal repetitive cycle. Cotton fabric/TiO2 (Cot/TiO2) substrate exhibits a high SERS activity and excellent spectral repeatability. The developed substrate has an ultra-high stability that can withstand long-term preservation; it can even resist the corrosions of strong acid and alkali, as well as high temperature up to 100 °C and low temperature down to - 20 °C. The flexible substrate can be used to carry out a rapid in situ detection for quinolone antibiotic (enrofloxacin and enoxacin) residues on the fish body surface by using a simple swabbing method, with high quantitative detection potential (up to an order of magnitude of 10-7 M), and even for the simultaneous detection of both drug residues. The flexible substrate also exhibits an excellent recyclability up to 6 recycles in the actual SERS detection.

Pyrazine-Functionalized Donor-Acceptor Covalent Organic Frameworks for Enhanced Photocatalytic H2 Evolution with High Proton Transport.

The well-defined 2D or 3D structure of covalent organic frameworks (COFs) makes it have great potential in photoelectric conversion and ions conduction fields. Herein, a new donor-accepter (D-A) COF material, named PyPz-COF, constructed from electron donor 4,4',4″,4'″-(pyrene-1,3,6,8-tetrayl)tetraaniline and electron accepter 4,4'-(pyrazine-2,5-diyl)dibenzaldehyde with an ordered and stable π-conjugated structure is reported. Interestingly, the introduction of pyrazine ring endows the PyPz-COF a distinct optical, electrochemical, charge-transfer properties, and also brings plentiful CN groups that enrich the proton by hydrogen bonds to enhance the photocatalysis performance. Thus, PyPz-COF exhibits a significantly improved photocatalytic hydrogen generation performance up to 7542 µmol g-1 h-1 with Pt as cocatalyst, also in clear contrast to that of PyTp-COF without pyrazine introduction (1714 µmol g-1 h-1 ). Moreover, the abundant nitrogen sites of the pyrazine ring and the well-defined 1D nanochannels enable the as-prepared COFs to immobilize H3 PO4 proton carriers in COFs through hydrogen bond confinement. The resulting material has an impressive proton conduction up to 8.10 × 10-2 S cm-1 at 353 K, 98% RH. This work will inspire the design and synthesis of COF-based materials with both efficient photocatalysis and proton conduction performance in the future.

Enhanced photocatalytic activity of Ag@g-C3N4 nanotubes by regulating photogenerated carriers to bypass the recombination center under the Lorentz force.

Photocatalysis, as a form of solar energy conversion, has considerable development prospects for solving energy exhaustion and environmental pollution. Promoting the utilisation of photocarriers is the key way to enhance photocatalytic activity and quantum efficiency. The g-C3N4 with the width of the band gap responsive to visible light, which is a great concern for researchers, was prepared by thermal decomposition and the insides were stripped from the outer wall and then curled to form the nanotubes (NTs), microtubes and shorten the migration distance of the electrons and holes. To promote the separation of the photocarriers in the g-C3N4, Ag particles are deposited by photoreduction as electron "traps" with surface plasmon resonance (SPR), and an external magnetic field is introduced during the photocatalysis. Under the Lorentz force, the photocatalytic efficiency of the Ag@g-C3N4 NTs is 200% higher than that of bulk g-C3N4, as a result of being able to prolong the life of the photogenerated carriers to bypass the recombination sites.

New insight in algal cell adhesion and cake layer evolution in algal-related membrane processes: Size-fractioned particles, initial foulant seeds and EDEM simulation.

A clear understanding of algal cell adhesion and cake layer evolution in algal-related membrane processes (ARMPs) is urgently required to mitigate the membrane fouling. In this study, the effect of microparticles (10 µm-30 µm), subvisible particles (0.45 µm-10 µm), and ultrafine particles (50 kDa-0.45 µm) on the membrane fouling were explored based on the filtration performance through Hermia models, thermodynamic analysis, and simulation of extended discrete element method (EDEM). The results illustrated that microparticles played an important role in algal cell aggregation and the formation of initial clusters. Intermediate blocking fouling occurred when filtrating the subvisible particle, which facilitated internal adhesion and enhanced biofilm formation. In addition, the interfacial attractive force for the initial algal adhesion was obviously increased when the membrane surfaces were in high concentration of protein and polysaccharide. Moreover, the EDEM simulation demonstrated that subsequent particles, particularly the particles with small sizes, preferred to occupy the spaces among the previously deposited particles. This study provided new insights into the contributions of size-fractioned particles to initial fouling and their influence on the successive adhesion of other contaminants.

Effect of Na-ion intercalation on the thermal conductivity of carbon honeycomb nanostructure.

This work studies the thermal conductivity of Na-ion intercalated carbon honeycomb (CHC) via the combination of first-principles calculation and molecular dynamics simulation. The effects of ion concentration, ion charge, temperature, and strain are explored. The simulation results show that the thermal conductivity of CHC presents a nonmonotonic dependence on the ion concentration. The enhanced phonon scattering and increased phonon group velocities of CHC induced by its interaction with the Na ions are responsible for the nonmonotonic dependence. Both the increases in the ion charge and temperature reduce the thermal conductivity. In contrast, a compressive strain of around -3% can increase the thermal conductivity by eliminating the phonon softening effect caused by the volume expansion of CHC during the ion intercalation. However, further increasing the strain negatively or positively from -3% leads to a decrease in the thermal conductivity. The simulation results presented in this work are beneficial in understanding the thermal properties of CHC when it is used as an electrode in ion batteries and supercapacitors.

COVIDSum: A linguistically enriched SciBERT-based summarization model for COVID-19 scientific papers.

The coronavirus disease (COVID-19) has claimed the lives of over 350,000 people and infected more than 173 million people worldwide, it triggers researchers from diverse fields are accelerating their research to help diagnostics, therapies, and vaccines. Researchers also publish their recent research progress through scientific papers. However, manually writing the abstract of a paper is time-consuming, and it increases the writing burden of the researchers. Abstractive summarization technique which automatically provides researchers reliable draft abstracts, can alleviate this problem. In this work, we propose a linguistically enriched SciBERT-based summarization model for COVID-19 scientific papers, named COVIDSum. Specifically, we first extract salient sentences from source papers and construct word co-occurrence graphs. Then, we adopt a SciBERT-based sequence encoder and a Graph Attention Networks-based graph encoder to encode sentences and word co-occurrence graphs, respectively. Finally, we fuse the above two encodings and generate an abstractive summary of each scientific paper. When evaluated on the publicly available COVID-19 open research dataset, the performance of our proposed model achieves significant improvement compared with other document summarization models.

Flavokawain B alleviates LPS-induced acute lung injury via targeting myeloid differentiation factor 2.

Acute lung injury (ALI) is a sudden onset systemic inflammatory response. ALI causes severe morbidity and death and currently no effective pharmacological therapies exist. Natural products represent an excellent resource for discovering new drugs. Screening anti-inflammatory compounds from the natural product bank may offer viable candidates for molecular-based therapies for ALI. In this study, 165 natural compounds were screened for anti-inflammatory activity in lipopolysaccharide (LPS)-challenged macrophages. Among the screened compounds, flavokawain B (FKB) significantly reduced LPS-induced pro-inflammatory IL-6 secretion in macrophages. FKB also reduced the formation of LPS/TLR4/MD2 complex by competitively binding to MD2, suppressing downstream MAPK and NF-κB signaling activation. Finally, FKB treatment of mice reduced LPS-induced lung injury, systemic and local inflammatory cytokine production, and macrophage infiltration in lungs. These protective activities manifested as increased survival in the ALI model, and reduced mortality upon bacterial infection. In summary, we demonstrate that the natural product FKB protects against LPS-induced lung injury and sepsis by interacting with MD2 and inhibiting inflammatory responses. FKB may potentially serve as a therapeutic option for the treatment of ALI.

Pharmacological inhibition of MyD88 suppresses inflammation in tubular epithelial cells and prevents diabetic nephropathy in experimental mice.

Emerging evidence shows that chronic inflammation mediated by toll-like receptors (TLRs) contributes to diabetic nephropathy. Myeloid differentiation primary-response protein-88 (MyD88) is an essential adapter protein of all TLRs except TLR3 in innate immunity. It is unclear whether MyD88 could be a therapeutic target for diabetic nephropathy. Here, we used a new small-molecule MyD88 inhibitor, LM8, to examine the pharmacological inhibition of MyD88 in protecting kidneys from inflammatory injury in diabetes. We showed that MyD88 was significantly activated in the kidney of STZ-induced type 1 diabetic mice in tubular epithelial cells as well as in high glucose-treated rat tubular epithelial cells NRK-52E. In cultured tubular epithelial cells, we show that LM8 (2.5-10 µM) or MyD88 siRNA attenuated high-concentration glucose-induced inflammatory and fibrogenic responses through inhibition of MyD88-TLR4 interaction and downstream NF-κB activation. Treatment with LM8 (5, 10 mg/kg, i.g.) significantly reduced renal inflammation and fibrosis and preserved renal function in both type 1 and type 2 diabetic mice. These renoprotective effects were associated with reduced MyD88-TLR4 complex formation, suppressed NF-κB signaling, and prevention of inflammatory factor expression. Collectively, our results show that hyperglycemia activates MyD88 signaling cascade to induce renal inflammation, fibrosis, and dysfunction. Pharmacological inhibition of MyD88 may be a therapeutic approach to mitigate diabetic nephropathy and the inhibitor LM8 could be a potential candidate for such therapy.

Sustainability and carbon neutrality trends for microalgae-based wastewater treatment: A review.

As the global economy develops and the population increases, greenhouse gas emissions and wastewater discharge have become inevitable global problems. Conventional wastewater treatment processes produce direct or indirect greenhouse gas, which can intensify global warming. Microalgae-based wastewater treatment technology can not only purify wastewater and use the nutrients in wastewater to produce microalgae biomass, but it can also absorb CO2 in the atmosphere or flue gas through photosynthesis, which demonstrates great potential as a sustainable and economical wastewater treatment technology. This review highlights the multifaceted roles of microalgae in different types of wastewater treatment processes in terms of the extent of their bioremediation function and microalgae biomass production. In addition, various newly developed microalgae cultivation systems, especially biofilm cultivation systems, were further characterized systematically. The performance of different microalgae cultivation systems was studied and summarized. Current research on the technical approaches for the modification of the CO2 capture by microalgae and the maximization of CO2 transfer and conversion efficiency were also reviewed. This review serves as a useful and informative reference for the application of wastewater treatment and CO2 capture by microalgae, aiming to provide a reference for the realization of carbon neutrality in wastewater treatment systems.

Krüppel-homolog 1 exerts anti-metamorphic and vitellogenic functions in insects via phosphorylation-mediated recruitment of specific cofactors.

BACKGROUND: The zinc-finger transcription factor Krüppel-homolog 1 (Kr-h1) exerts a dual regulatory role during insect development by preventing precocious larval/nymphal metamorphosis and in stimulating aspects of adult reproduction such as vitellogenesis. However, how Kr-h1 functions both as a transcriptional repressor in juvenile metamorphosis and an activator in adult reproduction remains elusive. Here, we use the insect Locusta migratoria to dissect the molecular mechanism by which Kr-h1 functions as activator and repressor at these distinct developmental stages. RESULTS: We report that the kinase PKCα triggers Kr-h1 phosphorylation at the amino acid residue Ser154, a step essential for its dual functions. During juvenile stage, phosphorylated Kr-h1 recruits a corepressor, C-terminal binding protein (CtBP). The complex of phosphorylated Kr-h1 and CtBP represses the transcription of Ecdysone induced protein 93F (E93) and consequently prevents the juvenile-to-adult transition. In adult insects, phosphorylated Kr-h1 recruits a coactivator, CREB-binding protein (CBP), and promotes vitellogenesis by inducing the expression of Ribosomal protein L36. Furthermore, Kr-h1 phosphorylation with the concomitant inhibition of E93 transcription is evolutionarily conserved across insect orders. CONCLUSION: Our results suggest that Kr-h1 phosphorylation is indispensable for the recruitment of transcriptional cofactors, and for its anti-metamorphic and vitellogenic actions in insects. Our data shed new light on the understanding of Kr-h1 regulation and function in JH-regulated insect metamorphosis and reproduction.

Activation of Peracetic Acid with CuFe2O4 for Rhodamine B Degradation: Activation by Cu and the Contribution of Acetylperoxyl Radicals.

Advanced oxidation processes (AOPs) demonstrate great micropollutant degradation efficiency. In this study, CuFe2O4 was successfully used to activate peracetic acid (PAA) to remove Rhodamine B. Acetyl(per)oxyl radicals were the dominant species in this novel system. The addition of 2,4-hexadiene (2,4-HD) and Methanol (MeOH) significantly inhibited the degradation efficiency of Rhodamine B. The ≡Cu2+/≡Cu+ redox cycle dominated PAA activation, thereby producing organic radicals (R-O˙) including CH3C(O)O˙ and CH3C(O)OO˙, which accounted for the degradation of Rhodamine B. Increasing either the concentration of CuFe2O4 (0-100 mg/L) or PAA (10-100 mg/L) promoted the removal efficiency of this potent system. In addition, weakly acid to weakly alkali pH conditions (6-8) were suitable for pollutant removal. The addition of Humid acid (HA), HCO3-, and a small amount of Cl- (10-100 mmol·L-1) slightly inhibited the degradation of Rhodamine B. However, degradation was accelerated by the inclusion of high concentrations (200 mmol·L-1) of Cl-. After four iterations of catalyst recycling, the degradation efficiency remained stable and no additional functional group characteristic peaks were observed. Taking into consideration the reaction conditions, interfering substances, system stability, and pollutant-removal efficiency, the CuFe2O4/PAA system demonstrated great potential for the degradation of Rhodamine B.

The imidazopyridine derivative X22 prevents diabetic kidney dysfunction through inactivating NF-κB signaling.

Diabetic kidney disease (DKD) is considered a chronic inflammatory renal disease induced by hyperglycemia. Therefore, even meticulous control of blood glucose levels cannot prevent the progression of DKD efficiently. Management of the inflammatory response could be one of the most promising strategies for treatment. We previously validated an imidazopyridine derivative (X22) as an active compound in suppressing lipopolysaccharide-induced inflammation. However, its potential for protection against DKD has not been exanimated. In the present study, streptozotocin-induced type 1 diabetic mice were used to study the effect of X22 on DKD associated inflammation and fibrosis by Q-PCR and immunoblotting assays. The results showed that X22 significantly inhibited the production of inflammatory cytokines (IL-6, TNF-α) and fibrosis biomarkers. At the same time, kidney function was dramatically improved. To elucidate the mechanism of action of X22, we examined its effects on the NRK-52E cell line. Strikingly, X22 restored the protein level of IKB-α and blocked the nuclear translocation of P65. Collectively, the data indicate that X22 can attenuate diabetic kidney dysfunction and inflammatory injury and may represent a potential agent for the treatment of DKD. It could be a potential agent for use in the treatment of DKD.

Juvenile hormone-dependent Kazal-type serine protease inhibitor Greglin safeguards insect vitellogenesis and egg production.

In addition to preventing insect metamorphosis, juvenile hormone (JH) is known to stimulate aspects of insect reproduction. However, the molecular mechanisms of JH action in insect reproduction remain largely unknown. By reanalyzing the transcriptomic data from adults and other developmental stages of the migratory locust Locusta migratoria, we identified a gene coding for Kazal-type protease inhibitor, previously named Greglin. Greglin is specifically expressed in adult females and most abundant in the fat body and ovaries. Interestingly, Greglin is among the top 3 of highly expressed genes in adult female locusts, after 2 vitellogenin ( Vg) genes. Greglin is induced by JH and expressed at remarkably high levels in the vitellogenic stage. Knockdown of Greglin in adult female locusts results in accelerated degradation of serine protease substrate and significantly reduced levels of Greglin protein in hemolymph and ovaries. The consequent phenotypes include blocked oocyte maturation, arrested ovarian growth and shrunken follicular epithelium, as well as declines in egg number and hatchability. The data provide the first evidence, to our knowledge, that JH-dependent Greglin is involved in locust vitellogenesis and oocyte maturation likely by protecting vitellogenesis and other forms of yolk precursors from proteolysis. The result offers new insights into the regulation of JH and function of protease inhibitors in insect vitellogenesis, oocyte maturation and fecundity.-Guo, W., Wu, Z., Yang, L., Cai, Z., Zhao, L., Zhou, S. Juvenile hormone-dependent Kazal-type serine protease inhibitor Greglin safeguards insect vitellogenesis and egg production.

A cross-sectional study of job burnout, psychological attachment, and the career calling of Chinese doctors.

BACKGROUND: The main objectives of this study were as follows: (1) evaluate the prevalence of burnout syndrome among doctors, (2) establish associations with demographic factors in China, and (3) examine the mediating role of psychological attachment in the relationship between job burnout and career calling. METHODS: This cross-sectional survey was conducted by administering an online questionnaire in May 2016. The survey was performed across Thirty provinces. In total, A total of 3016 Chinese doctors were selected as participants, of which 2617 completed valid questionnaires (effective response rate: 86.77%). RESULTS: The overall prevalence of burnout symptoms among Chinese doctors was 85.79%. Little variance was reported for burnout symptoms according to age (Waldχ2 = 6.843, P < 0.05, OR < 1), professional title (Waldχ2 = 13.110, P < 0.05, OR > 1), and daily working hours (Waldχ2 = 7.226, P < 0.05, OR > 1). However, the burnout of Chinese doctors was found to be associated with psychological attachment (B = - 0.6433, P < 0.0001) and career calling (B = 0.3653, P < 0.0001); furthermore, psychological attachment (B = 0.2350, P < 0.001) mediated the relationship between job burnout and career calling. CONCLUSION: Burnout symptoms among Chinese doctors were prevalent and associated with age, professional title, and long working hours. Chinese doctors aged 20-30 experienced a much higher level of burnout symptoms. The longer hours doctors worked, the more likely they were at risk of burnout symptoms, especially among attending physicians. Doctors who endured high-level burnout tended to exhibit decreasing psychological attachment, which threatened their sense of career calling. Finally, this paper proposed related explanations for the function mechanisms based on both theoretical and practical perspectives.

Head-to-head comparative pharmacokinetic and biodistribution (PK/BD) study of two dexamethasone prodrug nanomedicines on lupus-prone NZB/WF1 mice.

HPMA copolymer-based dexamethasone prodrug (P-Dex) and PEG-based dexamethasone prodrug (PEG-Dex, ZSJ-0228) were previously found to passively target the inflamed kidney and provide potent and sustained resolution of nephritis in NZB/WF1 lupus-prone mice. While both prodrug nanomedicines effectively ameliorate lupus nephritis, they have demonstrated distinctively different safety profiles. To explore the underlining mechanisms of these differences, we conducted a head-to-head comparative PK/BD study of P-Dex and PEG-Dex on NZB/WF1 mice. Overall, the systemic organ/tissue exposures to P-Dex and Dex released from P-Dex were found to be significantly higher than those of PEG-Dex. The high prodrug concentrations were sustained in kidney for only 24 h, which cannot explain their lasting therapeutic efficacy (>1 month). P-Dex showed sustained presence in liver, spleen and adrenal gland, while the presence of PEG-Dex in these organs was transient. This difference in PK/BD profiles may explain PEG-Dex' superior safety than P-Dex.

Diffusion tensor imaging in the evaluation of the long-term efficacy of HBO2 therapy in rats after traumatic spinal cord injury.

Objective: This study explored the feasibility of diffusion tensor imaging (DTI) in the evaluation of the long-term efficacy of hyperbaric oxygen (HBO2) therapy in rats after traumatic spinal cord injury (TSCI) with different degrees of injury. Method: Adult Sprague-Dawley rats (total n = 60) were randomly separated into three groups of mild, moderate and severe TSCI (20 rats per group). Each group was then randomly divided into TSCI and TSCI+HBO2 subgroups (10 rats per subgroup). Basso Beattie and Bresnahan (BBB) scores and DTI parameters including fractional anisotropy (FA), mean apparent diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were collected at pre-TSCI and at 0, six and 24 hours, and three, seven, 14, 21, 28 and 56 days post-TSCI. Two-way repeated measures analysis of variance was used for comparison between the TSCI and TSCI+HBO2 subgroups over time in the mild, moderate and severe TSCI groups. Pearson correlation analysis was applied to analyze the correlations between BBB scores and DTI parameters. Results: BBB scores, FA, MD and RD values showed significant differences between the TSCI and TSCI+HBO2 subgroups over time in the mild, moderate and severe TSCI groups (all p<0.01). FA, MD and RD values were positively correlated with BBB scores in all TSCI and TSCI+HBO2 subgroups (all p<0.05). Conclusions: DTI parameters, especially MD, could quantifiably assess the long-term efficacy of HBO2 therapy and reflect the functional recovery in rats after TSCI with different degrees of injury.

A Macromolecular Janus Kinase (JAK) Inhibitor Prodrug Effectively Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

BACKGROUND: Tofacitinib (Tofa) has been approved for moderately to severely active ulcerative colitis (UC). To improve its therapeutic efficacy and limit dose-dependent toxicity, we developed a macromolecular prodrug of Tofa (P-Tofa). If the prodrug design improves the potency and duration of Tofa therapy, it would widen its therapeutic window, potentially leading to improved safety and better clinical management of UC. METHODS: P-Tofa was synthesized by conjugating Tofa to N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer via a cleavable carbamate linker. DSS-induced UC mouse model were treated with Tofa (daily oral gavage, from day 8), P-Tofa (single intravenous administration on day 8, dose equivalent to Tofa treatment) and saline. Healthy mice were used as a positive control. The therapeutic efficacy was evaluated using disease activity index (DAI), endoscopic score and end-point histology. The optical imaging, immunohistochemistry and flow cytometry were used to understand P-Tofa's working mechanism. RESULTS: DAI results suggested that a single dose P-Tofa treatment was more efficacious than dose equivalent daily Tofa treatment. Endoscopic evaluation and histology analyses confirmed that while both P-Tofa and Tofa protected the colon, P-Tofa treated group was observed with better colon integrity with less tissue damage. Optical imaging, flow cytometry and immunohistochemistry results showed that P-Tofa passively targeted the inflamed colon and being retained via cellular sequestration. CONCLUSIONS: Single intravenous administration of P-Tofa was more effective than dose equivalent daily oral Tofa gavage in ameliorating DSS-induced colitis. This observed superior therapeutic efficacy may be attributed to P-Tofa's passive targeting to and retention by the inflamed colon.

Metal-free SERS substrate based on rGO-TiO2-Fe3O4 nanohybrid: contribution from interfacial charge transfer and magnetic controllability.

The exploitation of new types of non-metal surface-enhanced Raman scattering (SERS) substrates with high performances and the exploration of enhancement mechanisms are of vital importance for the development of the SERS technology due to its potential prospects in both the spectroscopy and material fields. Here, a magnetic SERS-active substrate hybridized by reduced graphene oxide (rGO), TiO2 and Fe3O4 (rGO-TiO2-Fe3O4) was successfully prepared via the combination of a simple sol-hydrothermal method and a co-precipitation method. The as-synthesized rGO-TiO2-Fe3O4 nanohybrid not only exhibited outstanding SERS detection ability with high sensitivity and spectral reproducibility, but also could be recycled with high stability based on its self-cleaning capacity and magnetism. Exploiting these features, it could be used for the SERS detection of 4-mercaptobenzoic acid (4-MBA), 4-mercaptopyridine (4-MPy), 6-mercaptopurine monohydrate (6-MP), 1,2-di(4-pyridyl) ethylene (BPE) and p-aminobenzoic acid (PABA) with the detection limits of 1.0 × 10-10, 1.0 × 10-8, 1.0 × 10-10, 1.0 × 10-10 and 1.0 × 10-9 mol L-1, respectively; these are the highest SERS sensitivity values among those reported for semiconductor substrates and are even lower than that of noble metal substrates. Meanwhile, an SERS enhancement mechanism from the synergistic effects of the rGO, TiO2 and Fe3O4 components was proposed to explain the observed considerable SERS enhancement on rGO-TiO2-Fe3O4.