Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects.

Photothermal agents (PTAs) with minimized side effects are critical for transforming cancer photothermal therapy (PTT) into clinical applications. However, most currently available PTAs lack true selective activation to reduce side effects because of heavy spectral overlap between photothermal agents and their corresponding products. This study reports the construction of activatable PTAs with target-initiated large spectral separation for highly effective reduction of side effects. Such designed probes involve two H2O2-activatable PTAs, aza-BOD-B1 (single activatable site) and aza-BOD-B2 (multiple activatable site). After interacting with H2O2, aza-BOD-B1 only displays a mild absorption redshift (60 nm) from 750 nm to 810 nm with serious spectral overlap, resulting in a mild photothermal effect on normal tissues upon 808 nm light irradiation. In contrast, aza-BOD-B2 displays a large absorption spectral separation (150 nm) from 660 nm to 810 nm, achieving true selective activation to minimize side effects during PTT of cancer. Besides, in vitro and in vivo investigations demonstrated that aza-BOD-B2 can specifically induce photothermal ablation of cancer cells and tumors while leaving normal sites undamaged, whereas aza-BOD-B1 exhibits undesirable side effects on normal cells. Our study provides a practical solution to the problem of undesired side effects of phototherapy, an advance in precision medicine.

Effect of Patient-Controlled Epidural Analgesia (PCEA) Based on ERAS on Postoperative Recovery of Patients Undergoing Gynecological Laparoscopic Surgery.

Objective: To explore the effect of patient-controlled epidural analgesia (PCEA) based on enhanced recovery after surgery (ERAS) on the postoperative recovery of patients undergoing gynecological laparoscopic surgery. Methods: Between January 2019 and December 2020, 90 patients scheduled for gynecological laparoscopic surgery and assessed for eligibility were recruited and randomly assigned at a ratio of 1 : 1 to receive either conventional analgesic management (regular group) or PCEA based on ERAS (ERAS group). Comparisons of postoperative rehabilitation indicators, visual analogue scale (VAS) score, self-care ability, complications, and nursing satisfaction were conducted between the two groups. Results: The ERAS group had significantly shorter first exhaust time (FET), first defecation time (FDT), out-of-bed activity time (OAT), and length of stay (LOS) versus the regular group (P < 0.05). The VAS scores were significantly decreased after treatment, with lower results observed in the ERAS group (P < 0.05). The level of self-responsibility, self-concept, self-care skills, and health knowledge increased significantly in both groups after the intervention, and the ERAS group showed significantly higher results than the regular group (P < 0.05). The total incidence of complications in the ERAS group was significantly lower than that in the regular group (P < 0.05). Eligible patients given PCEA based on ERAS were associated with a higher nursing satisfaction (97.78%) versus conventional analgesic management (82.22%) (P < 0.05). Conclusion: The application of ERAS for postoperative PCEA management in gynecological laparoscopy provides promising results by effectively enhancing the quality of surgery and promoting rapid postoperative recovery, with a good safety profile.

Theranostic Nanoplatform with Hydrogen Sulfide Activatable NIR Responsiveness for Imaging-Guided On-Demand Drug Release.

NIR light responsive nanoplatforms hold great promise for on-demand drug release in precision cancer medicine. However, currently available systems utilize "always-on" photothermal transducers that lack target specificity, and thus inaccurately differentiate tumors from normal tissues. Developed here is a theranostic nanoplatform featuring H2 S-mediated in situ production of NIR photothermal agents for imaging-guided and photocontrolled drug release. The system targets H2 S-rich cancers. This nanoplatform shows H2 S-activatable NIR-II emission and NIR light controllable release of the drug Camptothecin-11. Upon administering the system to HCT116 tumor-bearing mice, the tumor is greatly suppressed with minimal side effects, arising from the synergy of the cancer-specific and NIR light activated therapy. This theranostic nanoplatform thus sheds light on precision medicine with guidance through NIR-II imaging.

Hydrogen Sulfide-Activatable Second Near-Infrared Fluorescent Nanoassemblies for Targeted Photothermal Cancer Therapy.

Near-infrared (NIR)-II fluorescence agents hold great promise for deep-tissue photothermal therapy (PTT) of cancers, which nevertheless remains restricted by the inherent nonspecificity and toxicity of PTT. In response to this challenge, we herein develop a hydrogen sulfide (H2S)-activatable nanostructured photothermal agent (Nano-PT) for site-specific NIR-II fluorescence-guided PTT of colorectal cancer (CRC). Our in vivo studies reveal that this theranostic Nano-PT probe is specifically activated in H2S-rich CRC tissues, whereas it is nonfunctional in normal tissues. Activation of Nano-PT not only emits NIR-II fluorescence with deeper tissue penetration ability than conventional fluorescent probes but also generates high NIR absorption resulting in efficient photothermal conversion under NIR laser irradiation. Importantly, we establish NIR-II imaging-guided PTT of CRC by applying the Nano-PT agent in tumor-bearing mice, which results in complete tumor regression with minimal nonspecific damages. Our studies thus shed light on the development of cancer biomarker-activated PTT for precision medicine.

Altered baseline brain activity with 72 h of simulated microgravity--initial evidence from resting-state fMRI.

To provide the basis and reference to further insights into the neural activity of the human brain in a microgravity environment, we discuss the amplitude changes of low-frequency brain activity fluctuations using a simulated microgravity model. Twelve male participants between 24 and 31 years old received resting-state fMRI scans in both a normal condition and after 72 hours in a -6° head down tilt (HDT). A paired sample t-test was used to test the amplitude differences of low-frequency brain activity fluctuations between these two conditions. With 72 hours in a -6° HDT, the participants showed a decreased amplitude of low-frequency fluctuations in the left thalamus compared with the normal condition (a combined threshold of P<0.005 and a minimum cluster size of 351 mm(3) (13 voxels), which corresponded with the corrected threshold of P<0.05 determined by AlphaSim). Our findings indicate that a gravity change-induced redistribution of body fluid may disrupt the function of the left thalamus in the resting state, which may contribute to reduced motor control abilities and multiple executive functions in astronauts in a microgravity environment.