Near-Infrared Light-Activatable DNA Tentacles for Efficient Inhibition of Tumor Metastasis by Bio-Orthogonal Cell Assembly.

Tumor metastasis remains a major challenge in cancer management. Among various treatment strategies, immune cell-based cancer therapy holds a great potential for inhibiting metastasis. However, its wide application in cancer therapy is restricted by complex preparations, as well as inadequate homing and controllability. Herein, we present a groundbreaking approach for bioorthogonally manipulating tumor-NK (natural killer) cell assembly to inhibit tumor metastasis. Multiple dibenzocyclootyne (DBCO) groups decorated long single-stranded DNA were tail-modified on core-shell upconversion nanoparticles (CSUCNPs) and condensed by photosensitive chemical linker (PC-Linker) DNA to shield most of the DBCO groups. On the one hand, the light-triggered DNA scaffolds formed a cross-linked network by click chemistry, effectively impeding tumor cell migration. On the other hand, the efficient cellular assembly facilitated the effective communication between tumor cells and NK-92 cells, leading to enhanced immune response against tumors and further suppression of tumor metastasis. These features make our strategy highly applicable to a wide range of metastatic cancers.

UV-B Radiation Disrupts Membrane Lipid Organization and Suppresses Protein Mobility of GmNARK in Arabidopsis.

While it is well known that plants interpret UV-B as an environmental cue and a potential stressor influencing their growth and development, the specific effects of UV-B-induced oxidative stress on the dynamics of membrane lipids and proteins remain underexplored. Here, we demonstrate that UV-B exposure notably increases the formation of ordered lipid domains on the plasma membrane (PM) and significantly alters the behavior of the Glycine max nodule autoregulation receptor kinase (GmNARK) protein in Arabidopsis leaves. The GmNARK protein was located on the PM and accumulated as small particles in the cytoplasm. We found that UV-B irradiation interrupted the lateral diffusion of GmNARK proteins on the PM. Furthermore, UV-B light decreases the efficiency of surface molecule internalization by clathrin-mediated endocytosis (CME). In brief, UV-B irradiation increased the proportion of the ordered lipid phase and disrupted clathrin-dependent endocytosis; thus, the endocytic trafficking and lateral mobility of GmNARK protein on the plasma membrane are crucial for nodule formation tuning. Our results revealed a novel role of low-intensity UV-B stress in altering the organization of the plasma membrane and the dynamics of membrane-associated proteins.

Feasible CT features to distinguish incidental rib enhancement from sclerotic metastasis in patients with malignancies.

OBJECTIVE: To investigate the CT features of incidental rib enhancement (RE) and to summarize the CT characteristics for distinguishing the RE from sclerotic metastasis (SM) in patients with malignancies. MATERIAL AND METHODS: This retrospective observational study enrolled 79 patients with RE (involved 133 ribs) during October 2014 and December 2021. Another 53 patients with SM (160 SM) in the same period were selected randomly for comparison. The location, enhancement patterns of RE were reviewed. The CT values of RE regions and SM were measured and statistically analyzed. RESULTS: Most REs (70 patients, 88.6%) were in the 1st to 6th ribs. 50 patients had solitary RE and 29 with multiple REs in a regional distribution. All the REs were closely connected to the intercostal venous plexus (ICVP) ipsilateral to the injection site. No visible abnormalities on unenhanced scans were detected in all REs. One hundred and twenty REs (90.2%) had nodular/patchy enhancement. The CT value of RE regions in the venous phase was lower than that in the arterial phase (589.8 ± 344.2 HU versus 1188.5 ± 325.3 HU, p < 0.001). During the venous phase, most REs (125, 94.0%) shrank or disappeared. SM appeared similar on both contrast-enhanced and unenhanced scans in terms of shape and CT values. CONCLUSION: The RE demonstrated characteristic CT features. The manifestations of nodular/patchy enhancement in the arterial phase, decreased density and shrinkage or disappearance during the venous phase, and no abnormality on unenhanced scans, as well as a close connection with the ICVP, may help differentiate RE from SM.

Improving glutathione production by engineered Pichia pastoris: strain construction and optimal precursor feeding.

Glutathione (GSH) is a metabolite that plays an important role in the fields of pharmacy, food, and cosmetics. Thus, it is necessary to increase its production to meet the demands. In this study, ScGSH1, ScGSH2, and StGshF were heterologously expressed in Pichia pastoris GS115 to realize the dual-path synthesis of GSH in yeast. To explore the effects of ATP metabolism on the synthesis of GSH, enzymes (ScADK1, PpADK1, VsVHB) of the ATP-related metabolic pathway and the energy co-substrate sodium citrate were taken into account. We found that both ScADK1 and sodium citrate had a positive influence on the synthesis of GSH. Then, a fermentation experiment in Erlenmeyer flasks was performed using the G3-SF strain (containing ScGSH1, ScGSH2, StGshF, and ScADK1), with the highest GSH titer and yield of 999.33 ± 47.26 mg/L and 91.53 ± 4.70 mg/g, respectively. Finally, the fermentation was scaled up in a 5-L fermentor, and the highest titer and yield were improved to 5680 mg/L and 45.13 mg/g, respectively, by optimizing the addition conditions of amino acids (40 mM added after 40 h). Our work provides an alternative strategy by combining dual-path synthesis with energy metabolism regulation and precursor feeding to improve GSH production. Key Points • ScGSH1, ScGSH2, and StGshF were overexpressed to achieve dual-path synthesis of GSH in yeast. • ScADK1 was overexpressed, and sodium citrate was added to increase the energy supply for GSH synthesis. • The addition conditions of amino acids were optimized to realize the efficient synthesis of GSH.

Laser therapy versus topical desensitising agents in the management of dentine hypersensitivity: A meta-analysis.

OBJECTIVES: To compare the effectiveness of lasers and topical desensitising agent treatments for dentine hypersensitivity. METHODS: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and ISI Web of Knowledge were electronically searched without restrictions. Study search, selection, data extraction and assessment of risk of bias were conducted independently by two reviewer authors. All analyses were performed using Review Manager 5.3 (Cochrane Collaboration). RESULTS: This meta-analysis included 13 eligible studies that compared topical desensitising agents and Nd:YAG or diode laser. Four, six and three studies were considered to have low, moderate and high risks of bias, respectively. The follow-up period varied from immediate to 9 months. All comparisons except the 3-month Nd:YAG laser parallel group and 6-month diode laser group showed that the clinical efficacy of lasers for dentine hypersensitivity was not significantly different with topical desensitising agents. CONCLUSION: We found low-quality evidence that was insufficient to draw any conclusions regarding the superiority of lasers or conventional topical desensitising agents in the treatment of DH. Further well-designed RCTs on this topic are needed to draw definitive conclusions.