Selenium-Containing Nanocomplexes Achieve Dual Immune Checkpoint Blockade for NK Cell Reinvigoration.

The blockade of immune checkpoints has emerged as a promising strategy for cancer immunotherapy. However, most of the current approaches focus on T cells, leaving natural killer (NK) cell-mediated therapeutic strategies rarely explored. Here, a selenium-containing nanocomplex is developed that acts as a dual immune checkpoint inhibitor to reinvigorate NK cell-based cancer immunotherapy. The Se nanocomplex can deliver and release siRNA that targets programmed death ligand-1 (PD-L1) in tumor cells, thereby silencing the checkpoint receptor PD-L1. The intracellular reactive oxygen species generated by porphyrin derivatives in the nanocomplexes can oxidize the diselenide bond into seleninic acid, which blocks the expression of another checkpoint receptor, human leukocyte antigen E. The blockade of dual immune checkpoints shows synergistic effects on promoting NK cell-mediated antitumoral activity. This study provides a new strategy to reinvigorate NK cell immunity for the development of combined cancer immunotherapy.

Knowledge, Practices and Attitudes towards Silver Diamine Fluoride Therapy among Dentists in Japan: A Mixed Methods Study.

In 2021, the World Health Organization included silver diamine fluoride (SDF) as an essential medicine to manage caries in adults and children. SDF was developed in the 1960s, but its use for children became unpopular in Japan because of the decline and low prevalence of early childhood caries. This mixed methods study explored the knowledge, practices and attitudes towards SDF therapy among dentists promoting fluoride use in Japan. It also investigated senior dentists' perceptions of SDF therapy in Japan. The quantitative study invited all 173 members of the largest organisation promoting fluoride use in Japan to complete a web-based questionnaire survey. Sixty (60/173; 35%) dentists promoting fluoride use in Japan completed the questionnaire survey. All dentists knew of SDF treatment, and 50 (50/60; 83%) used SDF for dental care. Fifty-nine dentists (59/60; 98%) agreed that SDF therapy was simple and quick. All 60 dentists agreed that SDF was effective to arrest caries; 51 dentists (51/60; 85%) agreed that SDF was effective to prevent caries. Most dentists (51/60; 85%) were concerned about SDF's unaesthetic staining. Fifty-seven dentists (57/60; 95%) used SDF to arrest primary posterior teeth, and 52 dentists (52/60; 87%) used SDF to arrest root caries. However, 25 dentists (25/60; 42%) did not use SDF to prevent caries in permanent teeth. The qualitative study interviewed 12 senior dentists using snowball sampling and achieved data saturation. The dentists opined that SDF therapy was effective, simple, painless, non-invasive and inexpensive. SDF is seldom used in Japan at present because of the unaesthetic black staining and the low prevalence of early childhood caries; however, it can regain popularity by arresting root caries in the aging population.

Carbonaceous composite membranes for peroxydisulfate activation to remove sulfamethoxazole in a real water matrix.

In this study, we fabricated carbonaceous composite membranes by loading integrated mats of nitrogen-doped graphene, reduced graphene oxide, and carbon nanotubes (NG/rGO/CNTs) on a nylon microfiltration substrate and employed it for in-situ catalytic oxidation by activating peroxydisulfate (PDS) for the removal of sulfamethoxazole (SMX) in a real water matrix. The impact of coexisting organics on the performance of carbonaceous catalysis was investigated in the continuous filtration mode. Reusability testing and radical quenching experiments revealed that the non-radical pathways of surface-activated persulfate mainly contributed to SMX degradation. A stable SMX removal flux (rSMX) of 22.15 mg m-2·h-1 was obtained in 24 h when tap water was filtered continuously under a low pressure of 1.78 bar and in a short contact time of 1.4 s, which was slightly lower than the rSMX of 23.03 mg m-2·h-1 performed with deionized water as the control group. In addition, higher contents of protein-, fulvic acid-, and humic acid-like organics resulted in membrane fouling and significantly suppressed SMX removal during long-term filtration. Changes in the production of sulfate ions and the Raman spectra of carbon mats indicated that organics prevent the structural defects of the carbon matrix from participating in PDS activation. Moreover, NG/rGO/CNTs composite membranes coupled with activated persulfate oxidation exhibited good self-cleaning ability, because membrane fouling could be partly reversed by restoring filtration pressure during operation. This study provides a novel and effective oxidation strategy for efficient SMX removal in water purification, allowing the application of carbonaceous catalysis for the selective degradation of emerging contaminants.

Accelerated FeIII/FeII redox cycle of Fenton reaction system using Pd/NH2-MIL-101(Cr) and hydrogen.

In this paper, a novel improvement in the catalytic Fenton reaction system named MHACF-NH2-MIL-101(Cr) was constructed based on H2 and Pd/NH2-MIL-101(Cr). The improved system would result in an accelerated reduction in FeIII, and provide a continuous and fast degradation efficiency of the 10 mg L-1 4-chlorophenol which was the model contaminant by using only trace level FeII. The activity of Pd/NH2-MIL-101(Cr) decreased from 100% to about 35% gradually during the six consecutive reaction cycles of 18 h. That could be attributed to the irreversible structural damage of NH2-MIL-101(Cr).

Side-Chain Selenium-Grafted Polymers Combining Antiangiogenesis Treatment with Photodynamic Therapy and Chemotherapy.

The abnormal tumor vasculature in solid tumors creates hypoxia and leads to compromising the delivery and anticancer efficiency of nanomedicine. Nanomaterials with intrinsic antiangiogenesis ability might normalize tumor vessels and improve the therapeutic effect of O2-related treatment like PDT. Herein, we designed and prepared ROS-responsive side-chain selenium-grafted polymers, which had potential antiangiogenic activity, as vehicles to load photodynamic therapeutic agent Ce6 and chemotherapeutic drug oridonin. Under NIR irradiation, the C-Se bonds on the side chain of polymers could be cleaved in the presence of 1O2 produced by Ce6 and further formed organic selenic acid through selenoxide elimination reaction. The generated seleninic acid could downregulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to inhibit angiogenesis and further relieve hypoxia. The released oridonin could significantly increase the intracellular ROS concentration. Both could modulate cancer cells' microenvironment to reinforce PDT. Therefore, these nanomedicines could be a good candidate for synergistic treatments of antiangiogenesis treatment, PDT, and chemotherapy.

CO/chemosensitization/antiangiogenesis synergistic therapy with H2O2-responsive diselenide-containing polymer.

Carbon monoxide (CO) therapy and antiangiogenesis therapy (AAT) are regarded as promising approaches for cancer treatment. However, the poor tumor targeting ability and inevitable side effects prevent their clinical application. In this study, we developed H2O2-responsive diselenide-containing micelles that combined CO therapy with chemosensitization therapy and AAT in a single system. Under the interaction of intratumoral H2O2, CO and gemcitabine (GEM) were released in situ from the micelles to reduce side effects, and CO significantly sensitized the chemotherapeutic effect of GEM by elevating the level of reactive oxygen species (ROS) in human gastric cancer AGS cells. Furthermore, diselenide bonds in the micelles were oxidized to seleninic acid in organic form, which suppressed the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) to realize AAT. This study provides an integrated solution to combine CO therapy with chemosensitization therapy and AAT together with good biocompatibility.

The in situ catalytic oxidation of sulfamethoxazole via peroxydisufate activation operated in a NG/rGO/CNTs composite membrane filtration.

Metal-free carbonaceous composite membranes have been proven to effectively drive novel in situ catalytic oxidation for the degradation of organic pollutants via persulfates activation. In this study, nitrogen-doped graphene (NG) was employed as a modifier to enhance the catalytic activity of the carbon mats by assembly with reduced graphene oxide (rGO) and carbon nanotubes (CNTs) on the top of a nylon supporter. The morphology and performance of the NG/rGO/CNTs composite membrane were compared to those obtained without the addition of NG (rGO/CNTs). Owing to the larger nanochannels for water delivery and stronger hydrophobicity on the surface, the NG/rGO/CNTs composite membrane shows a superior low-pressure filtration performance in favor of energy-saving operation. For the in situ catalytic oxidation of the NG/rGO/CNTs composite membrane through the activation of peroxydisufate (PDS), the average removal rate of sulfamethoxazole (SMX), one of frequently detected sulfonamide antibiotics in water, can reach 21.7 mg·m-2·h-1 under continuous filtration mode, which was 17% more rapid than that of the rGO/CNTs, resulting in significant detoxifying of the oxidation intermediates. Owing to the addition of NG into the carbon mats, the reactive nitrogen-doped sites identified by X-Ray photoelectron spectroscopy (XPS), such as pyridinic and graphitic N, played important roles in PDS activation, while both the radical and non-radical pathways were involved in in situ catalytic oxidation. According to the experimental evidence of the effects that solution environment has on the SMX removal and transmembrane pressure, the NG/rGO/CNTs composite membrane shows a relatively high resistance to changes in the solution pH, chloride ion inhibition, and background organics fouling. These results suggest a new approach to the application of activated persulfate oxidation in water treatment, such that improvements to the reaction stability warrant further investigation.

Correction: Determination of sulfonamides in blood using acetonitrile-salt aqueous two-phase extraction coupled with high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry.

Correction for 'Determination of sulfonamides in blood using acetonitrile-salt aqueous two-phase extraction coupled with high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry' by Wei Yu et al., Anal. Methods, 2013, 5, 5983-5989, DOI: 10.1039/C3AY40902C.

Anti-recurrence/metastasis and chemosensitization therapy with thioredoxin reductase-interfering drug delivery system.

Thioredoxin reductase (TrxR) is an essential mammalian enzyme that possesses a selenocysteine active site. TrxR is overexpressed in many malignant tumors and has a close relationship with apoptosis, drug resistance, recurrence and metastasis of tumors. Recently, TrxR has emerged as a promising target for anticancer therapy. Herein, we developed a TrxR-interfering drug delivery system (DDS) based on RGD-PEG-PUSeSe-PEG-RGD self-assembling micelles for imaging-guided gemcitabine (GEM) chemosensitization and anti-recurrence/metastasis therapy. The diselenide-containing micelles were degraded in response to TrxR stimuli for GEM releasing. In the meantime, the dissociated polymers' chain segments targeted the active site of TrxR via Se-Se/Se-S dynamic reactions for activity inhibition. This inhibition by the micelles not only provided chemosensitization, but reduced tumor recurrence/metastasis risk via the induction of residual tumor cell apoptosis by triggering ROS production post-chemotherapy. In this work, we took the transformation between Se-containing dynamic covalent bonds developed by our group from in vitro to in vivo, which furthered the knowledge on the biochemistry of selenium and provided aspects to develop new TrxR inhibitors. Overall, the TrxR-interfering DDS combined excellent antitumor effects for primary solid tumors with the inhibition of tumor recurrence/metastasis during post-treatment care, providing new perspectives for efficient cancer therapy.

Selenium-Containing Nanoparticles Combine the NK Cells Mediated Immunotherapy with Radiotherapy and Chemotherapy.

Considering the limited clinical benefits of individual approaches against malignancy, natural killer (NK) cell-mediated immunotherapy is increasingly utilized in combination with radiotherapy and target therapeutics. However, the interplay of targeted agents, immunotherapy, and radiotherapy is complex. An improved understanding of the effect of chemotherapy or radiotherapy on specific molecular pathways in immune cells would help to optimize the synergistic antitumor efficiency. In this study, the selenium-containing nanoparticles (NPs) could deliver the chemotherapeutic drug doxorubicin (DOX) to tumor sites by systemic administration. Radiation stimuli facilitate DOX release and enhance chemotherapy efficiency. Moreover, radiation could oxidize diselenide-containing NPs to seleninic acid, which have both synergistic antitumor effect and immunomodulatory activity through enhancing NK cells function. These results indicate that the selenium-containing NPs would be a potential approach to achieve simultaneous treatments of immunotherapy, chemotherapy, and radiotherapy by a simple but effective method.

Selenium-Containing Carrier-Free Assemblies with Aggregation-Induced Emission Property Combine Cancer Radiotherapy with Chemotherapy.

Developing multifunctional carrier-free nanomedicine with high efficacy attracts tremendous attention in cancer treatment. Here, we develop selenium-containing carrier-free assemblies with aggregation-induced emission (AIE) property, which achieve the combination of cancer radiotherapy with chemotherapy. Under γ-radiation, diselenide bonds in the assemblies can be cleaved to form seleninic acid, which exhibits anticancer activity by upregulating the reactive oxygen species (ROS) levels in cancer cells. The incorporation of AIE groups further endows the selenium-containing assemblies with the ability of bioimaging. Their self-assembly behavior change under γ-radiation can be consequently observed in situ. The system combines cancer radiotherapy with chemotherapy, which exhibits improved anticancer activity.

Ionic Liquid-based Hollow Fiber Liquid-Liquid-Liquid Microextraction Combined with Capillary Electrophoresis for the Determination of Sulfonamides in Aquaculture Waters.

Ionic liquid-based hollow-fiber liquid-liquid-liquid microextraction (IL-HF-LLLME) coupled to capillary electrophoresis (CE) has been developed for the determination of six sulfonamides (SAs) in aquaculture waters. A series of extraction parameters was optimized to enhance the extraction efficiency, which included type and pore size of hollow fiber, type and composition of extraction solvent, pH value of donor phase, the concentration of acceptor phase and the mass ratio of donor phase to acceptor phase along with extraction temperature and time. Under optimal conditions, the IL-HF-LLLME-CE method provided a wide liner range for six SAs from 2 to 1,000 µg L-1 (r2 ≥ 0.9995), the limits of the detection from 0.25 to 0.48 and the enrichment factors from 122 to 230, respectively. Relative standard deviations for intra- and interday precision were 1.4-5.3% and 1.8-7.5% (n = 5), respectively. The proposed method was successfully applied for the determination of trace-level SAs in seven real-world aquaculture water samples with good recoveries (80.4-100.7%). Also, sulfamerazine and sulfamethoxazole were detected at the level of 0.52-1.60 µg L-1 in two water samples. Due to its good sensitivity, simple operation, short analysis time and eco-friendliness, the developed method has a great application potential in analysis of trace SA residues in aquaculture waters.

Diselenide-Pemetrexed Assemblies for Combined Cancer Immuno-, Radio-, and Chemotherapies.

Immunotherapy has emerged as a promising new approach for cancer treatment. However, clinically available drugs have been limited until recently, and the antitumor efficacy of most cancer immunotherapies still needs to be improved. Herein, we develop diselenide-pemetrexed assemblies that combine natural killer (NK) cell-based cancer immunotherapy with radiotherapy and chemotherapy in a single system. The assemblies are prepared by co-assembly between pemetrexed and cytosine-containing diselenide through hydrogen bonds. Under γ-radiation, the hydrogen bonds are cleaved, resulting in the release of pemetrexed. At the same time, diselenide can be oxidized to seleninic acid, which suppresses the expression of human leukocyte antigen E (HLA-E) in cancer cells, thus activating the immune response of NK cells. In this way, cancer immunotherapy is combined with radiotherapy and chemotherapy, providing a new strategy for cancer treatment.

Selenoxide elimination manipulate the oxidative stress to improve the antitumor efficacy.

Selenoxide elimination reaction has been widely used in the field of organic synthesis. However, few studies have been conducted to apply this reaction in biodegradable nanomedicine. In this work, the selenoxide elimination reaction was used for cancer treatment via producing excess cellular reactive oxygen species (ROS) for the first time. The ß-seleno diesters and porphyrin derivates containing nanoparticle could be responsive to the intracellular ROS and produce acrylates through the elimination reaction. The acrylates would further deplete intracellular GSH in tumor cells and finally improved the anticancer activity in the mice tumor model. Different from traditional ROS-responsive nanomedicine, the elimination product of this reaction could regenerate cytotoxic ROS and specifically disturb the redox balance of tumor cells. This work would provide attractive avenues for the development of therapeutic strategies against cancer via synthesis of well-designed biodegradable polymers.

Determination of aflatoxins in milk sample with ionic liquid modified magnetic zeolitic imidazolate frameworks.

The ionic liquid (IL) was introduced to the synthesis system of magnetic zeolite imidazolate framework-8 (M/ZIF-8), which was benefit to the formation of binary imidazole and the co-modification of M/ZIF-8. The morphology and textural properties of ILM/ZIF-8 were characterized by SEM, TEM, BET and BJH. The crystal structural shape and size of MZIF-8 was unvaried with the interventional of IL. The ILM/ZIF-8 was applied to the concentration and determination of aflaoxins (AFB1, AFB2, AFG1 and AFG2) in milk samples based on magnetic solid phase extraction (MSPE) coupled with ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The experimental parameters of the MSPE, including amount of ILM/ZIF-8, pH, type and amount of desorption solvent, extraction time and sample volume were investigated by a univariate method and orthogonal screening. The four AFs were concentrated from the 20 mL milk when 90 mg ILM/ZIF-8 was used as magnetic adsorbent. The extraction efficiency of AFs was higher than 80.0% within 15 min. The limits of quantitative and detection were 7.5-26.7 and 2.3-8.1 ng/L, respectively. The proposed method was applied to the determination of milk samples containing trace amounts of AFs and the recoveries ranged from 79.0% to 102.5%, with RSD below 7.7%.

Dental Caries and the Erosive Tooth Wear Status of 12-Year-Old Children in Jakarta, Indonesia.

BACKGROUND: Indonesia has the largest population of all countries in southeast Asia. However, little information is available on the oral health status of Indonesian children. The aims of this study were to assess dental caries and erosive tooth wear in 12-year-old children in Jakarta, Indonesia and to investigate the associated risk factors. METHODS: Samples were selected using cluster sampling. Parents were asked to complete a self-administered questionnaire regarding their oral health knowledge, demographic information, their child's dietary habits, and oral health-related behaviors. Experience of caries and erosive tooth wear were recorded using the Decayed, Missing (due to caries), and Filled Teeth (DMFT) index and the Basic Erosive Wear Examination (BEWE) index, respectively. RESULTS: Of 779 children invited, 696 participated in the survey. Of these, 61% had experienced caries, and the mean DMFT score was 1.58. Almost all decay was untreated. Children who were female, who had a high frequency of soft drink intake, and whose father's educational level was low were more likely to have dental caries. Most children had at least one lesion of erosive tooth wear. Children whose mother's educational level was low were more likely to have erosive tooth wear. CONCLUSIONS: The prevalence of dental caries and erosive tooth wear was high in 12-year-old children in Jakarta. Their dietary habits and parental level of education were associated with the presence of these dental conditions.

Determination of microcystins in environmental water samples with ionic liquid magnetic graphene.

Microcystins is a class of monocyclic of heptapeptides with many different isomerides. It has become potential hazardous material in water environment for its toxic, distribution and stability. This project worked on a method for determination of trace microcystin (MC-LR and MC-RR) in environmental waters. The ionic liquid magnetic graphene (IL@MG) was prepared and applied to the concentration and determination of microcystins, based on magnetic solid phase extraction (MSPE), and coupled with ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The ionic liquid magnetic graphene was prepared by coprecipitatial synthesis and characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), specific surface area (BET), pore size distribution (BJH) and magnetic hysteresis loop. The experimental parameters of magnetic solid phase extraction, including amount of IL@MG, pH, extraction time and elution solvent were investigated by a univariate method and orthogonal screening. The method showed good linearity in the range of 0.01-10.0 g/L and 0.005-10.0 µg/L for MC-LR and MC-RR, when the pH of water samples was 4.00 and 10.0 mg adsorbents were used to extract targets for 18 min. The lowest detection limit was 0.414 ng/L and 0.216 ng/L for MC-LR and MC-RR respectively. The recoveries of the microcystins were in the range of 83.6-100.9%, and the relative standard deviation was less than 7.59%. The trace amount of MC-LR (0.020 µg/L) and MC-RR (0.003 µg/L and 0.021 µg/L) was detected in actural water samples. Attributed to its simple operator, low detection limit and high sensitivity, this method could be used for the detection of trace microcystins in water samples.

Humanization of fibroblast growth factor 1 single-chain antibody and validation for its antitumorigenic efficacy in breast cancer and glioma cells.

Single-chain variable fragment (scFv) antibodies are the smallest immunoglobulins with high antigen-binding affinity. We have previously reported that fibroblast growth factor 1 played pivotal roles in cancer development and generated a mouse scFv (mscFv1C9) could effectively prohibit cancer cell proliferation in vitro and in vivo. Here, we further humanized this scFv (hscFv1C9) using a structure-guided complementarity determining region grafting strategy. The purified hscFv1C9 maintained similar antigen-binding affinity and specificity as mscFv1C9, and it was capable of inhibiting growth of different tumours in vitro and in vivo. These data strongly suggested that hscFv1C9 has antitumour potentials.

Denitrification potential of riparian soils in relation to multiscale spatial environmental factors: a case study of a typical watershed, China.

The objective of this study was to test the hypothesis that environmental regulators of riparian zone soil denitrification potential differ according to spatial scale within a watershed; consequently, a second objective was to provide spatial strategies for conserving and restoring the purification function of runoff in riparian ecosystems. The results show that soil denitrification in riparian zones was more heterogeneous at the profile scale than at the cross-section and landscape scales. At the profile scale, biogeochemical factors (including soil total organic carbon, total nitrogen, and nitrate-nitrogen) were the major direct regulators of the spatial distribution of soil denitrification enzyme activity (DEA). At the cross-section scale, factors included distance from river bank and vegetation density, while landscape-scale factors, including topographic index, elevation, and land use types, indirectly regulated the spatial distribution of DEA. At the profile scale, soil DEA was greatest in the upper soil layers. At the cross-section scale, maximum soil DEA occurred in the mid-part of the riparian zone. At the landscape scale, soil DEA showed an increasing trend towards downstream sites, except for those in urbanized areas.