A Multifunctional Tissue-Engineering Hydrogel Aimed to Regulate Bacterial Ferroptosis-Like Death and Overcoming Infection Toward Bone Remodeling.

Infection is the most common complication after orthopedic surgery and can result in prolonged ailments such as chronic wounds, enlarged bone defects, and osteomyelitis. Iron, which is essential for bacterial metabolism and immune cell functions, is extremely important. Bacteria harness iron from nearby cells to promote biofilm formation, ensuring their survival. Iron deficiency within the infection microenvironment (IME) consequently hampers macrophage function, enabling further dissemination of the infection and hindering macrophage polarization to the M2 phenotype. Therefore, a novel approach is proposed to regulate macrophage polarization, aiming to restore the inflammatory immune environment. A composite hydrogel derived from natural polymers is developed to address infections and manage iron metabolism in macrophages. This IME-responsive hydrogel, named FCL-ECMH, is synthesized by encapsulating vermiculite functional core layers within a decellularized extracellular matrix hydrogel. It is noteworthy that FCL-ECMH can produce reactive oxygen species within the IME. Supplementary photothermal treatment enhances bacterial iron uptake, leading to ferroptosis-like death. This process also rejuvenates the iron-enriched macrophages around the IME, thereby enhancing their antibacterial and tissue repair functions. In vivo experiments confirmed the antibacterial and repair-promoting capabilities of FCL-ECMH, indicating its potential for clinical applications.

Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared photoactivatable ferroptosis-immunotherapy.

Enzymes provide a class of potential options to treat cancer, while the precise regulation of enzyme activities for effective and safe therapeutic actions has been poorly reported. Dual-enzyme decorated semiconducting polymer nanoagents for second near-infrared (NIR-II) photoactivatable ferroptosis-immunotherapy are reported in this study. Such nanoagents (termed SPHGA) consist of hemoglobin (Hb)-based semiconducting polymer (SP@Hb), adenosine deaminase (ADA) and glucose oxidase (GOx) with loadings in a thermal-responsive nanoparticle shell. NIR-II photoactivation of SPHGA results in the generation of heat to trigger on-demand releases of two enzymes (ADA and GOx) via destroying the thermal-responsive nanoparticle shells. In the tumor microenvironment, GOx oxidizes glucose to form hydrogen peroxide (H2O2), which promotes the Fenton reaction of iron in SP@Hb, resulting in an enhanced ferroptosis effect and immunogenic cell death (ICD). In addition, ADA degrades high-level adenosine to reverse the immunosuppressive microenvironment, thus amplifying antitumor immune responses. Via NIR-II photoactivatable ferroptosis-immunotherapy, SPHGA shows an improved effect to absolutely remove bilateral tumors and effectively suppress tumor metastases in subcutaneous 4T1 breast cancer models. This study presents a dual-enzyme-based nanoagent with controllable therapeutic actions for effective and precise cancer therapy.

Detection of microvascular damage of membranous nephropathy by MicroFlow imaging: a novel ultrasound technique.

Background: MicroFlow imaging (MFI) is a novel noninvasive ultrasound (US) technique that depicts microcirculatory blood vessels in the kidney while filtering out tissue motion and enhancing blood flow signals. We aimed to investigate the value of MFI for the detection of renal microvascular perfusion in chronic kidney disease caused by stage I-II membranous nephropathy (MN). Methods: Seventy-six participants including biopsy-proven MN (n=38) and healthy volunteers (n=38) were prospectively examined using MFI from March 2020 to December 2020. In addition, patients with MN were subdivided into a mild group, a moderate group, and a severe group based on the results of vascular pathology evaluation. All MFI images were analyzed by Image Pro Plus to obtain a cortical vascular index (VI). Basic patient information, relative US parameters and laboratory results were then acquired for each participant. Finally, after the univariate analysis among multiple groups, binary logistic regression (forward LR) and ordered logistic regression were used for multivariate analysis. Significance was set at P<0.05. Results: VI was significantly lower in MN patients compared with that of healthy controls (0.65±0.09 vs. 0.35±0.18, P<0.001). After multivariate analysis, we found that the exploratory diagnostic performance of VI [area under the curve (AUC): 0.94; 95% confidence interval (CI): 0.89-0.99] outperformed that of serum creatinine (Scr) (AUC: 0.87; 95% CI: 0.79-0.95) in identifying MN. We also observed considerable differences among MN groups in parameters including VI (P=0.006), estimated glomerular filtration rate (eGFR) (P=0.037), shape (P=0.013), and impression (P=0.007). In addition, in the group with mild vascular damage, the exploratory diagnostic performance of VI (AUC: 0.79; 95% CI: 0.64-0.94) was better than other parameters, such as eGFR (AUC: 0.63; 95% CI: 0.43-0.84). Conclusions: MFI detected abnormal renal microvascular perfusion in patients with MN (particularly in those with early vascular damage or preserved renal function) without the use of a contrast agent. Combining MFI with B-mode US can improve the predictive performance of traditional kidney US.

Optimizing FSH Concentration Modulation in the Short-Acting GnRH-a Long Protocol for IVF/ICSI: A Retrospective Study.

INTRODUCTION: Exogenous gonadotropin (Gn) is given to regulate follicle-stimulating hormone (FSH) levels to achieve optimal ovarian response in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The objective of this study was to analyze the optimal degree of change in FSH blood concentration with ovarian responsiveness in a short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol for IVF/ICSI. METHODS: This retrospective study was conducted at Changzhou Maternity and Child Health Hospital's Reproductive Center from May 2017 to May 2023. A total of 794 ovarian stimulation cycles for IVF/ICSI using the short-acting GnRH-a long protocol was included. Ovarian responsiveness was assessed based on the number of follicles > 14 mm on human chorionic gonadotropin (HCG) trigger day, refine-follicular output rate (Refine-FORT) and good quality embryos. Delta 1 referred to the change in FSH level between days 6-8 of gonadotropin usage and baseline FSH, while Delta 2 referred to the change in FSH level between HCG trigger day and days 6-8 of gonadotropin usage. Simple and multiple linear regression analysis were performed to adjust for confounding factors. RESULTS: The number of follicles > 14 mm on HCG trigger day was found to be the most suitable indicator for evaluating ovarian responsiveness compared to the number of follicles > 16 mm and the number of retrieved oocytes. When Delta 1 ranged from 1.94 to 3.37, the number of follicles > 14 mm on HCG trigger day was the highest. When Delta 1 ranged from 3.37 to 5.90, the Refine-FORT was the highest. However, when Delta 1 exceeded 5.90, the number of follicles > 14 mm on HCG trigger day, Refine-FORT and good quality embryo all significantly decreased. On the other hand, when Delta 2 was ≤ - 1.58, the number of follicles > 14 mm on HCG trigger day and the Refine-FORT were both the highest. CONCLUSION: This study identifies optimal Delta 1 and Delta 2 ranges for effective ovarian responsiveness in a short-acting GnRH-a long protocol for IVF/ICSI and introduces the novel measure of the number of follicles > 14 mm on HCG trigger day. The optimal range for Delta 1 was 1.94 to 3.37, and Delta 2 should be < - 1.58 for achieving a higher number and quality of oocytes.

Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer.

BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization. RESULTS: TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts. CONCLUSION: Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.

[Study on effects and mechanism of traditional Mongolian medicine wuweifengshi capsule on adjuvant arthritis in rats].

OBJECTIVE: To study the effects and immunoregulation mechanism of the traditional Mongolian medicine Wuweifengshi capsule on adjuvant arthritis (AA). METHOD: Wister rats were divided into several groups: normal group, AA model group, Wuweifengshi capsule groups (with low, moderate, high dose of 0.2, 0.4, 0.8 g x kg(-1) x d(-1) respectively), and Zhonglun-5 group (original dose of 1.68 g x kg(-1) x d(-1)). The edema degree, the level of IL-1beta, TNF-alpha, PGE2, NO and MDA and the activity of SOD in serum were detected. Through cell culture, the effects of the medicine on AA rat's splenic cell's multiplication capacity were studied. The influence of celiac macrophage cell culture fluid of AA rats' on C57BL/6J mice thymic cell multiplication capacity under the medicine was evaluated. RESULT: Wuweifengshi capsule showed an inhibiting function on the level of IL-1beta, TNF-alpha, PGE2, NO and increased the activity of SOD in serum, but showed no significant influence on MDA. It also inhibited the AA rat's splenic cell's multiplication capacity and the influence of celiac macrophage cell culture fluid of AA rat's on C57BL/6J mice thymic cell multiplication capacity. CONCLUSION: The anti-AA effect of Wuweifengshi capsule is possibly due to its inhibition of relevant cytokines and its adjustment of corresponding enzyme's activity and immunization organ's cell multiplication capacity.

Porous graphitized carbon for adsorptive removal of benzene and the electrothermal regeneration.

Graphitized carbons with mesoporous and macroporous structures were synthesized by a facile template-catalysis procedure using resorcinol and formaldehyde as carbon precursors and particulate hydrated metal oxides as both template and catalyst precursors. The materials were used as novel adsorbents for low-concentration benzene vapor. Furthermore, on the basis of the good electrical conductivities associated with the graphitized structures, an electrothermal desorption technique, which involved passing electric currents through the adsorbents to generate Joule heat, was employed to regenerate the saturated adsorbents and produce enriched benzene vapors. In comparison to microporous activated carbon, the porous graphitized carbons could afford a much quicker and more efficient regeneration by electrothermal desorption technique due to their enhanced conductivity and larger pore sizes. In addition, the concentration of the desorbed organics could be controlled by adjusting the applied voltages, which might be interesting for practical secondary treatment. It is promising that the joint utilization of porous graphitized carbon adsorbents and electrothermal desorption technique might develop effective and energy-saving processes for VOCs removal.