Mitochondrial-targeted brequinar liposome boosted mitochondrial-related ferroptosis for promoting checkpoint blockade immunotherapy in bladder cancer.

Checkpoint blockade immunotherapy (CBI) have exhibited remarkable benefits for cancer therapy. However, the low responsivity of CBI hinders its application in treatment of bladder cancer. Ferroptosis shows potential for increasing the responsivity of CBI by inducing immunogenic cell death (ICD) process. Herein, we developed a mitochondrial-targeted liposome loaded with brequinar (BQR) (BQR@MLipo) for enhancing the mitochondrial-related ferroptosis in bladder cancer in situ. It could be found that BQR@MLipo could selectively accumulate into mitochondria and inactivate dihydroorotate dehydrogenase (DHODH), which induced extensive mitochondrial lipid peroxidation and ROS, finally triggering ferroptosis of bladder cancer cells to boost the release of intracellular damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), adenosine triphosphate (ATP), high mobility group box 1 (HMGB1). In addition, BQR@MLipo further promoted the release of mtDNA into the cytoplasm to activate the cGAS-STING pathway for the secretion of IFN-ß, which would increase the cross-presentation of antigens by dendritic cells and macrophage phagocytosis. Furthermore, the in vivo studies revealed that BQR@MLipo could remarkably accumulate into the bladder tumor and successfully initiate the infiltration of CD8+ T cells into tumor microenvironment for enabling efficient CBI to inhibit bladder tumor growth. Therefore, BQR@MLipo may represent a clinically promising modality for enhancing CBI in bladder tumor.

A host-guest interaction activated Bobbitt oxidant for highly efficient oxidation of alcohols.

Host-guest complexation using hydrogen-bonded macrocycles was found to enable activation of the Bobbitt oxidant reagent, which greatly facilitates the highly efficient oxidation of unactivated primary alcohols. This work provides a complementary approach to the activation of Bobbitt's salt with shape-persistent macrocycles in supramolecular catalysis.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

Tightly-bound trion and bandgap engineering viaγ-ray irradiation in the monolayer transition metal dichalcogenide WSe2.

Afterγ-ray irradiation treatment, a monolayer tungsten diselenide could be transitioned into an n-doped semiconductor due to the anion vacancies created by the radiation. Transmission electron microscope studies showed clear chemical modulation with atomically sharp interface. Change in the lattice vibrational modes induced by passivation of oxygen is captured by Raman spectroscopy. The frequency shifts in both in-plane and out-of-plane modes are dependent linearly on the oxidation content. We observe a negative trion, which is a neutral exciton bound with an electron, in the photoluminescence spectra. The binding energy of this trion is estimated to be ∼90 meV, making it a tightly bound exciton. The first-principles calculation suggests that an increase in the anion vacancy population is generally accompanied by a transition from a direct gap material to an indirect one. This opens up a new venue to engineer the electronic properties of transition metal dichalcogenides by using irradiation.

γ-Ray irradiation-induced unprecedent optical, frictional and electrostatic performances on CVD-prepared monolayer WSe2.

Distinguishing from traditional working environments, we propose the harsh gamma radiation method to study the stability and reliability of the emerging two-dimensional (2D) quantum material tungsten diselenide (WSe2). Transmission electron microscopy studies showed clear chemical modulation with an atomically sharp interface, indicating that the selenium vacancy content increased with the irradiation dose. The WSe2 crystal could be transitioned into an n-doped semiconductor due to the anion vacancies created by radiation. Changes in the lattice vibrational modes induced by the passivation of oxygen was captured via Raman spectroscopy. The frequency shifts in both in-plane and out-of-plane modes are dependent linearly on the selenium vacancy content. The friction of WSe2 increases with the irradiation dose. Electrostatic properties were investigated by measuring the surface potential via Kelvin probe force microscopy. Due to different environments, molecular collisions lead to an increase in the concentration of vacancy defects, which made our results different from those previously reported. The first principles calculation suggests that an increase in the selenium vacancy population is generally accompanied by a transition from a direct gap material to an indirect one. This opens up a new venue to engineer the optical, frictional and electronic properties of transition metal dichalcogenides using irradiation.