Near-infrared Light-Triggered Size-Shrinkable theranostic nanomicelles for effective tumor targeting and regression.

Most nanomedicines with suitable sizes (normally 100-200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors. To this end, a near-infrared light (NIR) -triggered size-shrinkable micelle system (Fe3O4@AuNFs/DOX-M) coloaded antitumor drug doxorubicin (DOX) and biomodal imaging agent magnetic gold nanoflower (Fe3O4@AuNFs) was developed to achieve efficient theranostic of tumors. Upon the accumulation of Fe3O4@AuNFs/DOX-M in the tumor periphery, a NIR laser was irradiated near the tumor sites, and the loaded Fe3O4@Au NFs could convert the light energy to heat, which triggered the cleavage of DOX-M to the ultra-small micelles (∼5 nm), thus realizing the deep penetration of micelles and on-demand drug release. Moreover, Fe3O4@AuNFs in the micelles could also be used as CT/MRI dual-modal contrast agent to "visualize" the tumor. Up to 92.6 % of tumor inhibition was achieved for the developed Fe3O4@AuNFs/DOX-M under NIR irradiation. This versatile micelle system provided a promising drug carrier platform realizing efficient tumor dual-modal diagnosis and photothermal-chemotherapy integration.

Chitosan nanomedicines-engineered bifidobacteria complexes for effective colorectal tumor-targeted delivery of SN-38.

The clinical application of 7-ethyl hydroxy-camptothecin (SN-38) maintains challenges not only due to its poor solubility and stability but also the lack of effective carriers to actively deliver SN-38 to deep tumor sites. Although SN-38-based nanomedicines could improve the solubility and stability from different aspects, the tumor targeting efficiency remains very low. Leveraging the hypoxic taxis of bifidobacteria bifidum (B. bifi) to the deep tumor area, we report SN-38-based nanomedicines-engineered bifidobacterial complexes for effective tumor-targeted delivery. Firstly, SN-38 was covalently coupled with poly-L-glutamic acid (L-PGA) and obtained soluble polymeric prodrug L-PGA-SN38 to improve its solubility and stability. To prolong the drug release, L-PGA-SN38 was mildly complexed with chitosan to form nanomedicines, and nanomedicines engineered B. bifi were further elaborated via electrostatic interaction of the excess of cationic chitosan shell from nanomedicines and anionic teichoic acid from B. bifi. The engineered B. bifi complexes inherited the bioactivity of native B. bifi and exhibited distinctly enhanced accumulation at the tumor site. More importantly, significantly elevated anti-tumor efficacy was achieved after the treatment of CS-L-PGA-SN38 NPs/B. bifi complexes, with favorable tumor suppression up to 80%. Such a B. bifi-mediated delivery system offers a promising platform for effective drug delivery and enhanced drug accumulation in the hypoxia deep tumor with superior anti-tumor efficacy.

Regional odontodysplasia with facial cellulitis: a case report and literature review.

Regional odontodysplasia (ROD) is a localized developmental anomaly involving deciduous and permanent dentition, with a significant impact on patients. The affected teeth display unique ghost-like radiological characteristics, clinically manifesting as delayed tooth eruption, abnormal tooth morphology, and recurrent swelling of gingiva. In this paper, we report a case of a 2-year-old patient with ROD whose chief complaint was facial cellulitis. We analyze the medical history, clinical examination, radiographic findings, and histologic findings, and review the pathological features, pathogenesis, multidisciplinary diagnosis, and treatment of ROD. This rare case, which offers clinical samples for its further study, can provide a deeper study of ROD.

Towards a better understanding of the anaerobic/oxic/anoxic-aerobic granular sludge process (AOA-AGS) for simultaneous low-strength wastewater treatment and in situ sludge reduction from ambient to winter temperatures.

The new anaerobic/oxic/anoxic-aerobic granular sludge (AOA-AGS) merits the advantages of effective carbon utilization and low-carbon treatment. However, low temperature poses stressing concerns and the resisting mechanism remains much unknown. Herein, an AOA-AGS process was configured for simultaneous nitrification, denitrification and phosphorus removal (SNDPR) with low-strength wastewater from ambient (>15 °C) to winter temperatures (<15 °C). Results showed that simultaneously advanced nutrients removal, and dramatic in situ sludge reduction (Yobs of 0.093 g MLSS/g COD) were gained regardless of seasonally decreasing temperatures. Winter temperatures even amplified Candidatus Competibacter predominating from 20.11% to 34.74%, which laid the core basis for endogenous denitrification, sludge minimization and temperature resistance. A removal model was thus proposed given the observed functional groups, and doubts were also raised for future investigations. This study would aid a better understanding on the microbial ecology and engineering aspects of the new AOA-AGS process treating low-strength wastewater at low temperatures.

Escherichia coli Nissle 1917-driven microrobots for effective tumor targeted drug delivery and tumor regression.

Potent tumor regression remains challenging due to the lack of effective targeted drug delivery into deep tumors as well as the reduced susceptibility of cancer cells to anticancer agents in hypoxic environments. Bacteria-driven drug-delivery systems are promising carriers in overcoming targeting and diffusion limits that are inaccessible for conventional antitumor drugs. In this study, probiotic facultative anaerobe Escherichia coli Nissle 1917 (EcN) was functionalized and formed self-propelled microrobots to actively deliver therapeutic drug and photosensitizer to the deep hypoxic regions of tumors. Doxorubicin (Dox) was firstly modified with cis-aconityl anhydride (CA) and terminal thiol-decorated hydrazone derivative (Hyd-SH) through dual pH-sensitive amide and imine bonds, respectively. The functionalized CA-Dox-Hyd-SH was further coordinated with photosensitizer gold nanorods (AuNRs) and then conjugated to the surface of EcN. The resulting microrobots (EcN-Dox-Au) inherited the mobility characteristics and bioactivity of native EcN. Upon the irradiation of NIR laser, the microrobots exhibited enhanced tumor accumulation and penetration into the deep hypoxia tumor site. Strikingly, after 21 days of treatment with EcN-Dox-Au formulations, complete tumor regression was achieved without relapse for at least 53 days. This self-propelled strategy utilizing bacteria-driven microrobots provides a promising paradigm for enhancing drug penetration and elevating chemosensitivity, resulting in a superior antitumor effect. STATEMENT OF SIGNIFICANCE: Self-propelled Escherichia coli Nissle 1917 (EcN) - mediated microrobots are functionalized to co-deliver therapeutic drugs and photosensitizers to the deep tumor site. Anti-tumor drug doxorubicin (Dox) was modified through dual pH-sensitive bonds on both terminals and then linked with EcN and photosensitizer gold nanorods (AuNRs) to realize tumor microenvironment acidic pH-responsive drug release. Upon irradiation with a NIR laser near the tumor site, AuNRs produced a photothermal effect which realized the superficial tumor thermal ablation and increased the permeability of the tumor cell membrane to facilitate the penetration of microrobots. Moreover, the deep penetration of microrobots also enhanced the susceptibility of the cancer cells to Dox, and realized the complete tumor regression in the established breast cancer-bearing mice without recurrence using a lower dose of drug regimen.

Performance of anaerobic/oxic/anoxic simultaneous nitrification, denitrification and phosphorus removal system overwhelmingly dominated by Candidatus_Competibacter: Effect of aeration time.

The anaerobic/oxic/anoxic simultaneous nitrification, denitrification and phosphorus removal process (AOA-SNDPR) is a promising technology for enhanced biological wastewater treatment and in situ sludge reduction. Herein, effects of aeration time (90, 75, 60, 45, and 30 min, respectively) on the AOA-SNDPR were evaluated including simultaneous nutrients removal, sludge characteristics, and microbial community evolution, where the role of a denitrifying glycogen accumulating organisms, Candidatus_Competibacter, was re-explored given its overwhelming dominance. Results revealed that nitrogen removal was more vulnerable, and a moderate aeration period of 45-60 min favored nutrients removal most. Low observed sludge yields (Yobs) were obtained with decreased aeration (as low as 0.02-0.08 g MLSS/g COD), while MLVSS/MLSS got increased. The dominance of Candidatus_Competibacter was identified as the key to endogenous denitrifying and in situ sludge reduction. This study would aid the low carbon- and energy-efficient aeration strategy for AOA-SNDPR systems treating low-strength municipal wastewater.