Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

Hearing loss is one of the most common neurosensory disorders in humans,severely affecting pa-tients'quality of life with lack of ideal treatments.Its pathogenesis is related to oxidative stress,inflammation and apoptosis in the inner ear.Recent studies have demonstrated that members of the signal transducer and activator of transcriptions(STATs)family are involved in regulating gene expression in auditory cells during inner ear develop-ment and physiological activities such as apoptosis,oxidative stress,inflammation and autophagy during auditory disorders.In this paper,we review the research on STATs in inner ear development and hearing loss,and elucidate their specific molecular mechanisms,aiming to provide theoretical guidance and direction for the prevention and treatment of hearing loss.

OBJECTIVE The preference for social novelty is crucial to the social life of humans and rodents.However,the neural mechanisms underlying social novelty preference are poorly understood.Dorsal hippocampal CA3(dCA3)is an important brain area that responds to social defeat stress,and the neural circuitry of dCA3→lat-eral septum(LS)participates in the context-associated memory.Meanwhile,the parvafox nucleus(PFN)Foxb1+ neurons regulate the defensive reaction to life-threaten-ing situations.Therefore,we investigate a cell-specific cir-cuit of dCA3CaMKⅡα+→dorsal LSGABA+→PFNFoxb1+ in social novelty preference.METHODS Chronic social defeat stress(CSDS)and three-chamber social interaction test were performed in adult male C57BL/6J mice to detect social behaviors.Optogenetic and chemical-genetic experiments were conducted to regulate the circuit.RESULTS CSDS reduced the preference for social nov-elty in mice and the response of dCA3CaMKⅡα+ neurons dur-ing approach to an unfamiliar mouse was impaired by CSDS.Optogenetic inhibition of dCA3CaMKⅡα+→dLS pro-jection reduced the preference for the unfamiliar mouse versus a familiar mouse.Meanwhile,optogenetic activa-tion of dCA3CaMKⅡα+→dLS projection rescued the prefer-ence for social novelty of CSDS-treated mice.Manipula-tions dLSGABA+→PFN projection activation regulated the preference for social novelty in mice.Optogenetic activa-tion of PFNFoxb1+→lPAG projection reduced the prefer-ence for a familiar C57BL/6J mouse versus a novel object in control mice.CSDS decreased the excitability of dCA3CaMKⅡα+ neurons by up-regulation of Kir2.4(Kcnj14)expression.CONCLUSION Our present study suggest-ed that activation of a cell-specific circuit of dCA3CaMKⅡα+→dLSGABA+→PFNFoxb1+→lPAG reverses the deficits of social novelty preference in defeated mice,and inhibition of this circuit reduces the preference for social novelty.The cir-cuit that regulates the preference for social novelty deficits may provide a new information for the potential therapeu-tic targets for neuropsychiatric diseases.

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood.The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis.The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Objective: To observe the evaluation function of gated equilibration ventriculography for the changes of left ventricular function in breast cancer with targeted therapy. Methods: From February 2016 to December 2017, a total of 60 female breast cancer patients (age: 28-65 (48.7±9.4) years) were included prospectively. Patients were divided into 2 groups: lapatinib combined with taxeme-based chemotherapy group (group A; n=25, age: 29-65 (47.8±11.3) years) and lapatinib monotherapy group (group B; n=35, age: 31-62 (51.1±8.5) years). All patients underwent gated equilibration ventriculography before treatment and 6/12 months after treatment. The parameters of left ventricular function including left ventricle ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), 1/3 ejection fraction (EF), 1/3 filling fraction (FF), time to peak ejection rate (TPER) and time of peak filling rate (TPFR) were observed. Repeated measurement analysis of variance, independent-samples t test and Wilcoxon rank sum test were performed. Results: In group A, the PER at 12 months after treatment ((3.11±0.48) end-diastolic volume (EDV)/s) was lower than that before treatment ((3.60±0.62) EDV/s; F=3.447, t=0.60, P<0.05), while there was no statistical difference between PER at 6 months after treatment ((3.34±0.57) EDV/s) and that before treatment (t=0.51, P>0.05); the PFR at 6 months ((3.07±0.71) EDV/s) and 12 months after treatment ((2.84±0.54) EDV/s) declined significantly compared with that before treatment ((3.57±0.81) EDV/s; F=5.345, t=0.82 and 0.75, both P<0.05). In group B, the PFR at 12 months after treatment ((2.86±0.55) EDV/s) declined significantly compared with that before treatment ((3.23±0.87) EDV/s; F=3.214, t=0.84, P<0.05). The decrease of PFR at 6 months and 12 months after treatment in group A was greater than that in group B (-0.37(-0.78, 0.15) vs -0.13(-0.44, 0.17) EDV/s; z=-1.569, P<0.05). Conclusions The gated equilibration ventriculography can effectively monitor the left ventricular function of breast cancer patients after targeted therapy. PER and PFR may be more sensitive than other parameters to assess heart function changes. The lapatinib combined with taxeme-based chemotherapy can affect diastolic function more and earlier than lapatinib monotherapy.

Objective:To determine expression levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and serum glial fibrillary acidic protein (GFAP) in patients with acute cerebral infarction and their clinical significance.Methods:A total of 80 patients with acute cerebral infarction in Chongqing Cancer Hospital from January 2014 to February 2016 were enrolled as an observation group.Another 80 healthy people served as a control group.The expression levels of UCH-L1 and GFAP in the 2 groups were detected.Results:Sensibility and specificity for UCH-L1 and GFAP were 75.0％,87.5％ and 81.3％,90.0％,respectively.Receiver operating characteristic curve areas of UCH-L1 and GFAP were 0.670 and 0.757,respectively.There were no significant significance in age,gender,drinking,smoke,diabetes,and hyperlipidemia in the 2 groups (P＞0.05).High blood pressure rate in the observation group was higher than that in the control group (P＜0.05).Spearson/Pearson analysis showed that serum UCH-L1 and GFAP levels were positively correlated with hypertension,but they were negatively correlated with sex,age,diabetes,hyperlipidemia,alcohol consumption,smoking,and other factors.General data at different time in the observation group was not statistically different (P＞0.05).The expression levels of UCH-L1 and GFAP in the observation group was higher than that in the control group (P＜0.05).UCH-L1 and GFAP levels at different time in the 2 groups were not statistically different (P＞0.05).UCH-L1 and GFAP levels in the light,medium,and heavy groups were higher than those in the control group (P＜0.05),while UCH-L1 and GFAP levels in the medium and heavy groups were higher than those in the light group (P＜0.05).There was significant difference between levels of UCH-L1 or GFAP and infarction size at different time in the observation group (P＜0.05).The results of Pearson correlation analysis showed that the levels of serum UCH-L1 and GFAP were positively correlated (r=0.634,P=0.001).Conclusion:The levels of serum UCH-L1 and GFAP are significantly increased at the early stage of acute cerebral infarction,and they have a certain correlation with the severity of cerebral infarction,which can provide a basis for early clinical diagnosis and treatment.

The specific human immunoglobulin is a hyperimmune globulin against a particular pathogen or biotoxin .It′s an important variety in plasma derivatives .Specific human immunoglobulin is usually used to prevent and treat pathogen in -fections with high morbidity , severe outcomes and no efficient treatment available .Thus it has unique advantages in preven-tion and management of infectious diseases .A variety of specific human immunoglobulins have been licensed abroad , but the development of new specific human immunoglobulins is slow in China due to technical constraints , limited economic benefits or for other reasons .Here we reviewed some specific human immunoglobulins and their preventive and therapeutic effect on infectious diseases .

Air Pollutants ; analysis ; Environmental Monitoring ; methods ; Esters ; analysis