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Background Immune checkpoint inhibitors (ICIs) are under extensive investigation as a treatment for triple-negative breast cancer (TNBC) in numerous trials. Given the need to evaluate their therapeutic profile, we conducted this systematic review and meta-analysis to comprehensively assess the safety and efficacy of ICI therapy for TNBC. Methods We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published in English from inception to March 10, 2024. Primary endpoints included treatment-related adverse events (trAEs) of any grade and Grade ≥ 3, as well as immune-related adverse events (irAEs). Results Thirteen RCTs involving 5,890 TNBC patients were included in the meta-analysis. ICI treatment was associated with a significantly increased risk of serious trAEs (risk ratio [RR]: 1.41; 95% confidence interval [CI]: 1.12–1.79; p  = 0.004) but did not significantly affect the risk of any grade trAEs (RR: 1.00; 95% CI: 0.99–1.02; p  = 0.584) or grade ≥ 3 trAEs (RR: 1.01; 95% CI: 0.87–1.18; p  = 0.872). In contrast, ICIs markedly elevated the risk of any grade irAEs (RR: 1.54; 95% CI: 1.22–1.95; p  < 0.001) and grade ≥ 3 irAEs (RR: 2.82; 95% CI: 1.56–5.11; p  = 0.001). Specific irAEs, including hypothyroidism, hyperthyroidism, pneumonitis, adrenal insufficiency, and infusion-related reactions, occurred more frequently with ICI therapy. Network meta-analysis revealed that atezolizumab had the lowest risk of any grade irAEs (surface under the cumulative ranking curve [SUCRA]: 60%) and grade ≥ 3 irAEs (SUCRA: 66%). Importantly, ICIs significantly improved pathological complete response (pCR) rates (RR: 1.55; 95% CI: 1.25–1.94; p  < 0.001) and were associated with enhanced overall survival (hazard ratio [HR]: 0.84; 95% CI: 0.74–0.96; p  = 0.011) and progression-free survival (HR: 0.69; 95% CI: 0.61–0.79; p  < 0.001). Conclusion While ICIs demonstrate clinically meaningful benefits in pCR rates and survival outcomes for TNBC patients, they also substantially increase the risk of serious trAEs and irAEs, including hypothyroidism, hyperthyroidism, pneumonitis, adrenal insufficiency, and infusion-related reactions. Registration INPLASY202450094.

Sensing bioelectrical signals is of great significance to understand human disease. Reliable bioelectronic interface is the guarantee of high‐quality bioelectrical signals. The unique electrochemical property and the mixed ionic and electrical conductivity of poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) make it an ideal material for the skin/tissue–electronic interface. However, pristine PEDOT:PSS‐based devices cannot meet the requirements for practical use. Toward this end, herein, the development of PEDOT:PSS‐based electrodes and their most recent advances in sensing bioelectrical signals are summarized. First, the generation mechanism of bioelectrical signals is introduced in detail. Then, according to the characteristics of bioelectrical signals, the requirements of bioelectrodes are discussed. Next, representative achievements for improving conductivity, stretchability, and stability of PEDOT:PSS are introduced. Bioelectrical signals such as electromyogram (EMG), electrocardiogram (ECG), electrooculogram (EOG), and electroencephalogram (EEG) are successfully recorded by these PEDOT:PSS‐based electrodes. Finally, a brief summary is provided, and the opportunities and challenges are also discussed. The development of poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)‐based electrodes and their most recent advances in sensing bioelectrical signals are summarized The generation mechanism of bioelectrical signals, the requirements of bioelectrodes, representative achievements of improving conductivity, stretchability and stability of PEDOT:PSS, and recent application of epidermal and implantable PEDOT:PSS electrodes are reviewed, and the opportunities and challenges are discussed.

Nelumbo nucifera has great value and development prospects in hypolipidemic applications. In this study, we comprehensively screened out multi–index components relevant to the quality of N. nucifera based on the hypolipidemic function of the flavonoid fraction of N. nucifera (FFN) combined with chemical characterizations. Firstly, in vitro antioxidant and cell experiments evaluated the hypolipidemic function of the FFN. Secondly, the chemical compositions of N. nucifera were identified by UPLS–MSn technology. Then, the multi–index flavonoid components (rutin, hyperoside, isoquercitrin, quercetin–3–O–β–D–glucuronide, astragalin, and quercetin) were determined using a quantitative fingerprint combined with multivariate statistical data analysis. Finally, the quality of N. nucifera was scientifically evaluated by multi–index quantitative analysis combined with multivariate statistical data analysis, which was used to study the relationship between the content of flavonoid components and the overall quality. The above–mentioned research lays a material foundation for improving the quality standards of N. nucifera, providing a basis for developing functional foods to improve dyslipidemia.

Nelumbinis folium (N. folium) exhibits hypolipidemic effects and shows great potential for application in lipid-lowering drugs and healthcare products. This study aimed to investigate the mechanism underlying the hypolipidemic effects of the alkaloid fraction of N. folium (AFN). Animal experiments demonstrated that AFN significantly reduced blood lipid levels and ameliorated liver damage in hyperlipidemic mice. RNA-seq analysis identified 26 reverse-regulated differentially expressed genes (DEGs), which were primarily involved in the PPAR signaling pathway, fat digestion and absorption, and fatty acid degradation. Using UPLC-MSn, 30 plasma-absorbed components were identified, including 13 prototype alkaloids. Among these, three key active components—nuciferine, N-nornuciferine, and N-methylisococlaurine—were screened via network topology analysis. Molecular docking revealed strong binding affinities between these compounds and key targets. The results showed that N-methylisococlaurine bound to SLC27A4 and CPT1A with strong affinity, while nuciferine and N-nornuciferine bound to ACADVL and PPARA. RT-qPCR results confirmed that AFN modulates the expression of FABP1, SLC27A4, PPARA, CPT1A, ACAA2, APOC3, and APOA4. These findings suggest that AFN exerts its hypolipidemic effects through multi-component, multi-target, and multi-pathway mechanisms.

Non-invasive collection of weak electroneurographic signals is crucial for cognitive neuroscience. However, animal scalps are often covered by dense hair, which presents a substantial barrier in the scalp-electrode interface for accurate electrophysiological acquisition. Although scalp hair removal is common practice in clinical settings, it has detrimental effects on the test subjects and is infeasible in many non-clinical scenarios. Here we report a hair-adaptable and adhesion-tunable (HAAT) scalp-electrode interface that can accurately acquire electroneurographic signals from hairy skins of animal and human. By synthetically integrating dynamic covalent bonds and ionic conduction channels in the copolymer poly(sodium thioctate- co -sulfobetaine methacrylate), we implement the key functionalities of the HAAT interface including penetration of dense hair layers, strong conformal skin-electrode adhesion, on-demand painless detachment, and sensitive neuroelectric coupling. We achieve stable and precise electroneurographic signals acquisition from human, monkey and mouse’s scalps with various hair densities. The accurate event-related potential monitored during monkey vision-attention tasks facilitates the study of monkey brain activity. These results demonstrate the HAAT interface as an outstanding platform for conducting non-invasive research on animal cognition. Hair hampers scalp electrophysiology, yet shaving is often impractical. Here, the authors demonstrate an adhesive gel for high-quality EEG via dynamic covalent bonding and ion conductive polymers.

Stroke is a significant global burden, causing extensive morbidity and mortality. In metabolic states where glucose is limited, ketone bodies, predominantly β-hydroxybutyrate (BHB), act as alternative fuel sources. Elevated levels of BHB have been found in the ischemic hemispheres of animal models of stroke, supporting its role in the pathophysiology of cerebral ischemia. Clinically, higher serum and urinary BHB concentrations have been associated with adverse outcomes in ischemic stroke, highlighting its potential utility as a prognostic biomarker. In both animal and cellular models, exogenous BHB administration has exhibited neuroprotective effects, reduction of infarct size, and improvement of neurological outcomes. In this review, we focus on the role of BHB before and after ischemic stroke, with an emphasis on the therapeutic potential and mechanisms of ketone administration after ischemic stroke.

Virtual reality (VR) is increasingly used as a distraction tool for painful procedures in children. Studies have shown variable benefit but have not identified factors to maximize utility. This study aimed to undertake a feasibility study to investigate factors influencing virtual reality headset (VRH) utility for venipuncture and cannulation. Children admitted as inpatients were recruited and given a VRH during anticipated venipuncture or cannulation. Feedback from participants, parents, and operators was obtained through questionnaires and the Wong-Baker Faces Scale (WBFS). Thirteen children of a target 32 (41%), aged a median of 7 (range 5-12) years, were recruited to the study; 9 (69%) parents and 7 (54%) participants reported a positive VR experience, found VRH comfortable, and wanted repeat application for future venisection or cannulation. However, patient recruitment was suboptimal at 41% (binomial 95% CI 24%-59%) of the target, as busy operators undertaking venisection or cannulation on eligible patients were unable to spare time for VRH use during the COVID-19 pandemic. The preprocedure time spent with VRH was associated with participants' positive experience of VR distraction (median 15, IQR 2.5-50 vs 180, IQR 120-450) seconds (P=.02). Five (38.4%) participants removed the VRH prior to procedure; these were relatively young compared to those who continued VRH (median 6, IQR 5.00-7.00 vs 10, IQR 6.75-12.00 years), suggesting better acceptance of VR in older children. There was no significant difference in WBFS pain ratings before (median 0, IQR 0-10) or after the procedure (median 0, IQR 0-6), with many children choosing 0 (\"no hurt\") at initial assessment. By contrast, parent and doctor or phlebotomist responses indicated that VR reduced pain and anxiety (n=9, 69%), in agreement with participant perception (n=7, 54%; Cohen κ=0.68). VR as a distraction tool in children is influenced by age and preprocedure familiarity, suggesting that the optimal use is in older children with greater cognitive and emotional maturity. Multidimensional feedback from participants, parents, and investigators should be obtained to test the true efficacy of VR in future studies.

ContextJiang-Zhi-Ning (JZN), a traditional Chinese medicinal formula, is used to treat hyperlipidemia in clinics.ObjectiveTo screen the hypolipidemic “bioequivalent substance system (BSS)” of JZN and elucidate the potential hypolipidemic mechanism.Materials and methodsIn vitro, the TG content in HepG2 cells was determined after the intervention of the combination of advantageous components (CAC) by uniform design. In vivo, hyperlipidemia models were established by Triton WR-1339 (400 mg/kg; i.p.) in male ICR mice, and corresponding treatments were administered via oral administration once. The mice were divided into 12 groups (n = 5): control, hyperlipidemic model, simvastatin (positive control, 20 mg/kg), gradient doses of JZN granules (2, 4 and 8 g/kg) and the hypolipidemic effective extraction (HEE) of JZN (120, 240 and 480 mg/kg) and CAC groups (20, 40 and 160 mg/kg). Serum TC, TG, LDL-C and HDL-C were performed after 24 h. Transcriptomics and qRT–PCR technology were used to explore the mechanism of the “BSS” of JZN.ResultsIn vitro, the ratio of CAC was determined. CAC could reduce the TG content in HepG2 cells (77.21%). Compared with the model group, the high dose of CAC could markedly decrease the levels of TC (61.86%), TG (105.54%) and LDL-C (39.38%) and increase the level of HDL-C (232.67%). CAC was proved to be the “BSS”. Transcriptomics and qRT–PCR analysis revealed CAC regulated non-alcoholic fatty liver disease, bile secretion, PPAR and adipocytokine signalling pathway.Discussion and conclusionsThese findings provided new feasible ideas and methods for the elucidation of the pharmacodynamic material basis.

Claudins (CLDNs) play a crucial role in regulating the permeability of epithelial barriers and can impact tumor behavior through alterations in their expression. However, the precise mechanisms underlying the involvement of CLDNs in breast cancer progression remain unclear. This study aimed to investigate the role of CLDN11 in breast cancer progression. Utilizing the TCGA database and clinical specimens from breast cancer patients, we observed reduced expression of CLDN11 in tumor tissues, which correlated with poor prognosis in breast cancer patients. In vitro, silencing of CLDN11 enhanced the proliferative and migratory characteristics of breast cancer cell lines MCF-7 and MDA-MB-231. Mechanistically, CLDN11 deficiency promoted the upregulation of Forkhead Box M1 (FOXM1) by activating the hedgehog signaling pathway, thereby sustaining tumor progression in breast cancer. In vivo, blockade of hedgehog signaling suppressed the tumor progression induced by CLDN11 silencing. Our study highlights the significance of the CLDN11/FOXM1 axis in breast cancer progression, suggesting CLDN11 as a potential diagnostic indicator and therapeutic target for clinical therapy.

Stroke is a significant global burden, causing extensive morbidity and mortality. In metabolic states where glucose is limited, ketone bodies, predominantly [beta]-hydroxybutyrate (BHB), act as alternative fuel sources. Elevated levels of BHB have been found in the ischemic hemispheres of animal models of stroke, supporting its role in the pathophysiology of cerebral ischemia. Clinically, higher serum and urinary BHB concentrations have been associated with adverse outcomes in ischemic stroke, highlighting its potential utility as a prognostic biomarker. In both animal and cellular models, exogenous BHB administration has exhibited neuroprotective effects, reduction of infarct size, and improvement of neurological outcomes. In this review, we focus on the role of BHB before and after ischemic stroke, with an emphasis on the therapeutic potential and mechanisms of ketone administration after ischemic stroke.