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Abstract Breast cancer is one of the most prevalent and diverse malignancies, and, with global cases increasing, the need for biomarkers to inform individual sensitivity to chemotherapeutics has never been greater. Our retrospective clinical analysis predicted that the expression of the fragile site-associated tumor suppressor (FATS) gene was associated with the sensitivity of breast cancer to neoadjuvant chemotherapy with paclitaxel. In vitro experiments subsequently demonstrated that FATS significantly increased the inhibitory effects of paclitaxel on breast cancer cells’ migration, growth, and survival. An interaction screen revealed that FATS interacted with MYH9 and promoted its degradation via the ubiquitin-proteasome pathway, thereby downregulating Wnt signaling. By overexpressing FATS and MYH9, we demonstrated that FATS enhanced paclitaxel-induced apoptosis in breast cancer cells by degrading MYH9 to downregulate the Wnt pathway. We also demonstrated in a mouse xenograft model that FATS significantly increased the chemosensitivity of breast cancer cells to paclitaxel in vivo. This study presents a new mechanism by which FATS interacts with MYH9 to suppress the Wnt/β-catenin signaling pathway and induce apoptosis, thus enhancing the sensitivity of breast cancer cells to paclitaxel chemotherapy. The results also propose novel biomarkers for predicting breast cancer sensitivity to neoadjuvant chemotherapy with paclitaxel. Finally, we provide in vivo evidence that the combination of paclitaxel with IWR-1, a novel Wnt pathway inhibitor, synergistically suppresses breast cancer growth, laying the foundation for future trials with this drug combination. These results therefore provide a number of potential solutions for more precise treatment of patients with breast cancer in the future.

Abstract Rhein, a component derived from rhubarb, has been proven to possess anti-inflammatory properties. Here, we show that rhein mitigates obesity by promoting adipose tissue thermogenesis in diet-induced obese mice. We construct a macrophage-adipocyte co-culture system and demonstrate that rhein promotes adipocyte thermogenesis through inhibiting NLRP3 inflammasome activation in macrophages. Moreover, clues from acetylome analysis identify SIRT2 as a potential drug target of rhein. We further verify that rhein directly interacts with SIRT2 and inhibits NLRP3 inflammasome activation in a SIRT2-dependent way. Myeloid knockdown of SIRT2 abrogates adipose tissue thermogenesis and metabolic benefits in obese mice induced by rhein. Together, our findings elucidate that rhein inhibits NLRP3 inflammasome activation in macrophages by regulating SIRT2, and thus promotes white adipose tissue thermogenesis during obesity. These findings uncover the molecular mechanism underlying the anti-inflammatory and anti-obesity effects of rhein, and suggest that rhein may become a potential drug for treating obesity.

Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages. Upon skin insertion, dual nanocomplexes are released rapidly from the MN and accumulate in RA joint microenvironment through both passive and active targeting as mediated by HSA. Thioketal-crosslinked fluorinated polyethyleneimine 1.8 K (TKPF) was constructed to bind the plasmid encoding pro-apoptotic gene PUMA with HSA coating layer (TKPF/pPUMA@HSA, TPH). TPH nanocomplexes can upregulate PUMA through RA FLS transfection to trigger efficient apoptosis. Also, HSA nanocomplexes encapsulating the classic anti-inflammatory natural product celastrol (Cel@HSA, CH) can inhibit inflammation of macrophages through blocking NF-κB pathway activation. TPH/CH MN can deplete RA FLS and inhibit M1 macrophage activation, suppress synovial hyperplasia as well as reduce bone and cartilage erosion in a collagen-induced arthritis (CIA) mouse model, demonstrating a promising strategy for efficient RA treatment.

The research progress in chemical crosslinking and filler enhancement of tetrapropyl fluoro elastomer was reviewed at home and abroad with 39 references. The key roles of co-crosslinkers and fillers were elucidated in the construction of crosslinking networks. The aging mechanism of tetrapropyl fluoro elastomer was summarized syste-matically under environmental conditions such as heat, oxygen, acid and alkali, and hydrogen sulfide.

Abstract Elastocaloric cooling has emerged as an eco-friendly technology capable of eliminating greenhouse-gas refrigerants. However, its development is limited by the large driving force and low efficiency in uniaxial loading modes. Here, we present a low-force and energy-efficient elastocaloric air cooling approach based on coil-bending of NiTi ribbons/wires. Our air cooler achieves continuous cold outlet air with a temperature drop of 10.6 K and a specific cooling power of 2.5 W g−1 at a low specific driving force of 26 N g−1. Notably, the cooler shows a system coefficient of performance of 3.7 (ratio of cooling power to rotational mechanical power). These values are realized by the large specific heat transfer area (12.6 cm2 g−1) and the constant cold zone of NiTi wires. Our coil-bending system exhibits a competitive performance among caloric air coolers.

Normalizing inflamed soils including reactive oxygen species (ROS), nitric oxide (NO), cell-free DNA, and regulating inflammation-related seeds such as macrophages, neutrophils, fibroblasts, represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis (RA) treatment. Herein, ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol (Not@BR/oPDA-PEG, NBOP NPs). The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation, but also decrease cytokines and chemokines to prevent immune cell recruitment. Specifically, NBOP NPs responded to high level ROS and NO, and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic ones. The released notopterol could inhibit the JAK-STAT pathway of inflammatory cells to reduce the secretion of pro-inflammatory cytokines and chemokines. This strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation, achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat model. Taken together, our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

Background: The objective of the study was to systematically evaluate the efficacy and safety of semaglutide in overweight or obese adults with or without type 2 diabetes. Materials and Methods: The study, registered with PROSPERO (CRD42023450979), was designed as a systematic review and meta-analysis. Using a combination of subject matter and free words, a comprehensive search of Embase, PubMed, and Cochrane Library databases was performed to identify randomized controlled trials of semaglutide in overweight or obese adults with or without Type 2 diabetes mellitus from January 1, 2020, to July 14, 2023. The primary outcomes were the changes in body weight and adverse drug reaction (ADR). Random or fixed effects models were used in meta-analysis, pooling data as relative risks (RRs) or mean difference (MD) with 95% confidence intervals (CIs). Cochrane Collaboration’s Risk of Bias tool was used to assess quality. Meta-analysis was performed using RevMan 5.3. Results: A total of 2490 publications were retrieved. Fifteen publications were finally included, totaling 6984 overweight or obese adult patients. Meta-analysis showed that compared with the control group, the semaglutide group was reduced more significantly in body weight (MD = −7.49, 95% CI [−9.92, −5.07], P < 0.001), body mass index (MD = −3.35, 95% CI [−4.79, −1.92], P < 0.001), waist circumference (MD = −7.26, 95% CI [−9.94, −4.58], P < 0.001), as well as glycosylated hemoglobin (RR = −0.66, 95% CI [−1.07, −0.25], P = 0.002), fasting blood glucose values (RR = −4.81, 95% CI [−7.03, −2.60], P < 0.001), and systolic blood pressure (RR = −3.37, 95% CI [−5.32, −1.42], P < 0.001), and the proportion of patients who lost > 5%, 10%, 15%, and 20% of their overall body weight, respectively (RR = 3.19, 95% CI [1.89, 5.36], P < 0.001), (RR = 4.74, 95% CI [2.78, 8.11], P < 0.001), (RR = 6.17, 95% CI [3.88, 9.82], P < 0.001), and (RR = 9.14, 95% CI [6.05, 13.80], P < 0.001) were also superior to the control group. Regarding safety, the incidence of total ADR in the semaglutide group was close to the placebo group. Still, gastrointestinal adverse effects such as nausea, vomiting, abdominal pain, and diarrhea were higher than those in the control group. Conclusion: Semaglutide can effectively lose weight in overweight or obese adults with or without diabetes, potentially providing cardiovascular benefits; however, gastrointestinal adverse should be closely monitored.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague–Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 μg/g) were significantly greater compared to the LF group (0.02 ± 0.01 μg/g, P

This review summarizes commonly used hospital-based healthcare quality evaluation systems at home and abroad, and focuses on evaluation indicators regarding patient safety. Through the comparative analysis between different evaluation systems, it tries to shed light on China's healthcare quality evaluation system, especially the indicators related to patient safety. The purpose of this review is to understand and learn from foreign evaluation systems on patient safety, which can help further improve the quality of healthcare in China.