Fluorescence imaging technique has been used for imaging of biological cells and tissues in vivo. The Cd-free luminescent quantum dots conjugating with a cancer targeting ligand has been taken as a promising biocompatibility and low cytotoxicity system for targeted cancer imaging. This work reports the synthesis of fluorescent-doped core/shell quantum dots of water-soluble manganese-doped zinc sulfide. Quantum dots of manganese-doped zinc sulfide were prepared by nucleation doping strategy, with 3-mercaptopropionic acid as stabilizer at 90 in aqueous solution. The manganese-doped zinc sulfide nanoparticles exhibit strong orange fluorescence under UV irradiation, resistance to photo-bleaching, and low-cytotoxicity to HeLa cells. The structure and optical properties of nanoparticles were characterized by scanning electron microscope, X-ray diffraction, dynamic light scattering, and photoluminescence emission spectroscopy. Manganese-doped zinc sulfide nanoparticles conjugated with folic acid using 2,2'-(ethylenedioxy)-bis-(ethylamine) as the linker. The covalent binding of both 2,2'-(ethylenedioxy)-bis-(ethylamine) and folic acid on the surface of manganese-doped zinc sulfide nanoparticles probed by Fourier transform infrared spectroscopy detection. Furthermore, in vitro cytotoxicity assessment of manganese-doped zinc sulfide-folic acid probes use HeLa cells. The obtained fluorescent probes (manganese-doped zinc sulfide) were used for tumor targeting and imaging in vivo. The manganese-doped zinc sulfide-folic acid fluorescent probes which targeting the tumor cells in the body of nude mouse tumor model would emit orange fluorescence, when exposed to a 365 nm lamp. We investigate the biodistribution of the manganese-doped zinc sulfide-folic acid fluorescent probes in tumor mouse model by measuring zinc concentration in tissues. These studies demonstrate the practicality of manganese-doped zinc sulfide-folic acid fluorescent probes as promising platform for tumor targeting and imaging in vivo.

Upconversion nanoparticles (UCNPs) are widely used in the field of biomedicine, such as biosensing, cell labeling and medical multimodal imaging because of their unique optical properties. In this paper, we demonstrated the synthesis of polyethylenimine-modified NaLuF4:Yb,Er ([Formula: see text], Yb[Formula: see text], Er[Formula: see text] UCNPs in three different solvents, such as water, ethylene glycol and diethylene glycol. The as-prepared UCNPs were characterized and the experimental results showed that the UCNPs synthesized in ethylene glycol had excellent properties. The obtained UCNPs in ethylene glycol had the smallest particle size and uniform size distribution, and the pure cubic phase of crystallization and Dynamic light scattering and particle dispersion index (DLS/Pdi) were the smallest. What’s more, the upconversion fluorescence intensity was 7 and 52 times greater than that of UCNPs synthesized in diethylene glycol and water, respectively. In addition, the factors of reaction solvent that had an impact on the particle size, morphology, crystalline phase, DLS and upconversion fluorescence intensity of the synthesized UCNPs were discussed. Moreover, in order to obtain the targeted nanoprobe, we used an EDC/NHS covalent coupling method to modify folic acid to the NaLuF4:Yb,Er/PEI UCNP surface. The NaLuF4:Yb,Er/PEI–FA upconversion fluorescent nanoprobes had low cytotoxicity and were suitable for the application in HeLa cells targeted fluorescent imaging.

Zinc (Zn), an essential trace element, can stimulate bone formation and inhibit osteoclastic bone resorption, which controls the growth and maintenance of bone. However, the effect of Zn supplementation on tricalcium phosphate (TCP) wear particles‐induced osteolysis remains unknown. Here, we doped Zn into TCP particles (ZnTCP), and explore the protective effects of Zn on TCP particles‐induced osteolysis in vivo. TCP particles and ZnTCP particles were embedded under the periosteum around the middle suture of the mouse calvaria. After 2 weeks, blood, the periosteal tissue, and the calvaria were collected to determine serum levels of Zn and osteocalcin, pro‐inflammatory cytokines, bone biochemical markers, osteoclastogenesis and bone resorption area, and to explain its mechanism. Data revealed that Zn significantly prevented TCP particles‐induced osteoclastogenesis and bone loss, and increased bone turnover. The Zn supplement remarkably suppressed the release of pro‐inflammatory cytokines including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, and IL‐6. Immunoblotting demonstrated that Zn alleviated expression levels of ER stress‐related proteins such as glucose‐regulated protein 78 (GRP78), PKR‐like ER kinase (PERK), phospho‐PERK (p‐PERK), eukaryotic initiation factor 2α (eIF2α), phospho‐eIF2α (p‐eIF2α), activating transcription factor 4 (ATF4), inositol‐requiring enzyme 1α (IRE1‐α) and transcription factor X‐box binding protein spliced (XBP1s), leading to decreasing the ratios of p‐PERK/PERK and p‐eIF2α/eIF2α. Taken together, Zn supplementation strongly prevents TCP particles‐induced periprosthetic osteolysis via inhibition of the ER stress pathway, and it may be a novel therapeutic approach for the treatment of aseptic prosthesis loosening.

Intracerebral microdialysis (IC-MD) has been developed as a well-validated and powerful technique for decades. As a practical sampling tool, it can gain the continuous dialysates of endogenous and exogenous substances in extracellular fluid (ECF) of awake freely moving animals. Also, variform IC-MD probes (IC-MDPs) have grown more exquisite. The implantation of the IC-MDP in certain tissue of brain allows monitor drug distribution and measure drug and corresponding neurotransmitters levels in brain ECF after administration for brain pharmacokinetic-pharmacodynamic (B-PK-PD) study. So it is suitable for IC-MD to B-PK-PD study (IC-MD/B-PK-PD). The performance of IC-MD/B-PK-PD can not only elevate the degree of precision and accuracy of experimental data, minimize the individual difference by reduced number of animals, but also give important information for the prediction and optimization of drug effective dose in preclinical study. In this review, we have discussed various IC-MD/B-PK-PD studies of analgesic, antiepileptic and antidepressant drug. The role of IC-MD/B-PK-PD in confirming and assessing the drug effect before clinic trials is highlighted.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.