Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

ObjectiveTo investigate the effect and potential mechanism of Dihuangyin on 2， 4-dinitrochlorobenzene （DNCB） -induced model mice with atopic dermatitis （AD）. MethodA mouse model with AD was established by repeatedly stimulating the back skin of mice with DNCB. After successful modeling， the mice were randomly divided into model group， Runzao group （0.78 g·kg^-1）， and high， medium， and low dose （40.30， 20.15， and 10.08 g·kg^-1） groups of Dihuangyin， with 12 mice in each group， and the blank group consisted of 12 mice， 72 in total. The administration groups were given the corresponding liquid by dose， and the blank group and model group were given the same dose of pure water by intragastric administration， once a day. The skin lesions and scratching times of mice were observed after continuous administration for two weeks. The back skin lesions of mice were stained with hematoxylin-eosin （HE） and toluidine blue to observe the pathology. The contents of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， and interferon-γ （IFN-γ） were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of IFN-γ， IL-4， IL-6， Janus kinase 1 （JAK1）， and transcriptional activator 3 （STAT3） in skin lesion tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of JAK1， phosphorylation（p）-JAK1， STAT3， and p-STAT3 proteins in skin lesion tissue were detected by Western blot. ResultCompared with the blank group， the back skin of the model group showed large-scale scab， dryness， erosion， hypertrophy with scratching， epidermal hyperplasia with hyperkeratosis and parakeratosis， hyperacanthosis with edema， and a large number of mast cell infiltration in the dermis， some of which were degranulated. The contents of IgE， IL-4， IL-6， and IFN-γ in the serum of mice were significantly increased （P<0.01）， and the protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly increased （P<0.01）. Compared with the model group， only a small amount of dryness and desquamation were observed in the back skin of mice in each administration group， and cell edema was reduced. The inflammatory infiltration was significantly reduced， and the number of mast cell infiltration was significantly decreased. The serum IgE， IL-4， IL-6， and IFN-γ of mice were decreased to varying degrees （P<0.05， P<0.01）. The protein expression levels of p-JAK1， STAT3， and p-STAT3 and mRNA expressions of IL-4， IL-6， IFN-γ， JAK1， and STAT3 in skin lesion tissue were significantly decreased， and the effect of high dose group of Dihuangyin was the best （P<0.01）. ConclusionDihuangyin can improve skin lesions and pruritus in mice with AD， and its mechanism may be related to the effective regulation of cytokines on the helper T cells （Th1）/Th2 axis by interfering with the JAK1/STAT3 signaling pathway and affecting skin barrier function.

Objective:To establish a bacterial endotoxin test method for nafamostat mesilate for injection.Methods:The interference test of the bacterial endotoxin test method-kinetic chromogenic assay was carried out according to the Chinese Pharmacopoeia 2020 Volume Ⅳ general chapter 1143.Results:The interference effect of naphtholimus mesylate can be effectively eliminated by treating the test solution with an alkaline regulator for a certain period of time and diluting it.Conclusion:The bacteria endotoxin test-kinetic chromogenic assay for nafa-mostat mesilate for injection is applicable.

Objective:To discuss the inhibitory effect of diosmetin(DIO)on the ferroptosis induced by the glutathione peroxidase(GSH-Px)inhibitor(1S,3R)-RSL3(RSL3)in spermatocytes GC-2 of the mice,and to clarify the mechanism.Methods:The GC-2 cells were divided into control group,RSL3 group,RSL3+0.8 nmol·L-1 DIO group,RSL3+4.0 nmol·L-1 DIO group,RSL3+20.0 nmol·L-1 DIO group,and RSL3+ferroptosis inhibitor Ferrostain-1(Fer-1)group(200 nmol·L-1 Fer-1).The cells were treated with 0,1,5,10,50,100,500,and 1 000 nmol·L-1 RSL3 solutions,and 0,0.5,0.1,1.0,5.0,10.0,and 50.0 μmol·L-1 DIO solutions,respectively.Additionally,the GC-2 cells were divided into blank group,model group,and treatment group.The GC-2 cells in treatment group were further divided into 0.8,4.0,and 20.0 nmol·L-1 DIO groups,as well as RSL3+0.8 nmol·L-1 DIO group,RSL3+4.0 nmol·L-1 DIO group,and RSL3+20.0 nmol·L-1 DIO group.MTT method was used to detect the survival rates of the GC-2 cells in various groups.The GC-2 cells were treated with 100 nmol·L-1 RSL3 for 0,6,12,24,36,and 48 h;Western blotting method was used to detect the expression levels of ferroptosis-related proteins in the GC-2 cells in various groups;kits were used to detect the activities of superoxide dismutase(SOD),levels of malondialdehyde(MDA),and ratios of glutathione(GSH)to glutathione disulfide(GSSG)in the GC-2 cells in various groups;immunofluorescence method was used to detect the fluorescence intensities of acyl-CoA synthetase long-chain family member 4(ACSL4)protein in the GC-2 cells in various groups.Results:The MTT method results showed that compared with 0 nmol·L-1 RSL3 group,the survival rates of the GC-2 cells in 50,100,500,and 1 000 nmol·L-1 RSL3 groups were significantly decreased(P<0.01);compared with 0 μmol·L-1 DIO group,the survival rates of the GC-2 cells in 0.5,1.0,5.0,10.0,and 50.0 μmol·L-1 DIO groups were significantly decreased(P<0.01),and 100 nmol·L-1 RSL3 with DIO concentration<0.1 μmol·L-1 were selected for the subsequent experiments.Compared with blank group,the survival rates of the GC-2 cells in model group was significantly decreased(P<0.01);compared with model group,the survival rates of the GC-2 cells in RSL3+20.0 nmol·L-1 DIO group was significantly increased(P<0.01).The Western blotting results showed that compared with 0 h,the expression level of GPX4 protein in the GC-2 cells was significantly decreased after treated with RSL3 for 6 h(P<0.01),and the expression level of HO-1 protein was significantly increased after treated with RSL3 for 12 h(P<0.05);after treated with RSL3 for 12 h,the expression levels of GPX4 and FTH1 proteins were significantly decreased(P<0.05 or P<0.01);after treated with RSL3 for 24 h,the expression levels of GPX4 and HO-1 proteins were significantly decreased(P<0.05 or P<0.01);after treated with RSL3 for 36 and 48 h,the expression levels of HO-1 protein were significantly decreased(P<0.01).Therefore,100 nmol·L-1 RSL3 and for 12 h were selected as the experimental condition for the subsequent experiments.Compared with control group,the MDA level in the GC-2 cells in RSL3 group was significantly increased(P<0.01),and the SOD activity and GSH/GSSG ratio were significantly decreased(P<0.05).Compared with RSL3 group,the SOD activities in the cells in RSL3+0.8 nmol·L-1 DIO group,RSL3+4.0 nmol·L-1 DIO group,RSL3+20.0 nmol·L-1 DIO group,and RSL3+Fer-1 group were significantly increased(P<0.05 or P<0.01).The MDA levels in the cells in RSL3+20.0 nmol·L-1 DIO group and RSL3+Fer-1 group were significantly decreased(P<0.05 or P<0.01),and the GSH/GSSG ratio in the cells in RSL3+4.0 nmol·L-1 DIO group,RSL3+20.0 nmol·L-1 DIO group,and RSL3+Fer-1 group were significantly increased(P<0.05 or P<0.01).The immunofluorescence observation results showed that compared with control group,the fluorescence intensity of ACSL4 protein in the GC-2 cells in RSL3 group was significantly increased;compared with RSL3 group,the fluorescence intensities of ACSL4 protein in the cells in RSL3+0.8 nmol·L-1 DIO group,RSL3+4.0 nmol·L-1 DIO group,RSL3+20.0 nmol·L-1 DIO group,and RSL3+Fer-1 group were significantly decreased.The Western blotting results showed that compared with control group,the expression level of HO-1 protein in the cells in RSL3 group was increased(P<0.05),and the expression levels of GPX4 and FTH1 proteins were significantly decreased(P<0.05 or P<0.01);compared with RSL3 group,the expression levels of HO-1 protein in the cells in RSL3+0.8 nmol·L-1 DIO group,RSL3+4.0 nmol·L-1 DIO group,RSL3+20.0 nmol·L-1 DIO group,and RSL3+Fer-1 group were significantly decreased(P<0.05 or P<0.01),and the expression levels of GPX4 and FTH1 proteins were significantly increased(P<0.05 or P<0.01).Conclusion:DIO can alleviate the RSL3-induced ferroptosis in the GC-2 spermatocytes of the mice,and its mechanism may be related to the inhibition of HO-1 protein expression and the upregulation of expressions of GPX4 and FTH1 proteins.

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

Objective:To investigate the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation in patients with mild carotid artery stenosis.Methods:A retrospective study was conducted to select 30 cases of patients with unilateral mild carotid artery stenosis and moderate intensity aerobic exercise for more than 1 year in the Central Hospital of Dalian University of Technology from July 2022 to November 2023 as the exercise group (study group), and 30 cases of patients with unilateral mild carotid artery stenosis without exercise habits matched by age, gender and other factors as the non-exercise group (control group). Transcranial Doppler ultrasound (TCD) examination was performed in both groups, and the recumbent-upright-test, breath holding test and breath exchange test were performed to calculate the occurrence rate of "w" wave in recumbent-upright position, the slope of "w" wave in recubitus position, the change rate of pulse index (PI) before and after breath holding, resistance index (RI), breath holding index (BHI), and cerebral blood flow velocity before and after breath exchange. The blood pressure and heart rate difference in the recumbent-upright position were calculated, and the correlation between moderate intensity aerobic exercise and cerebral blood flow regulation function in patients with mild carotid artery stenosis was evaluated by statistical analysis. The correlation analysis between the exercise years and BHI in the study group was carried out to explore the relationship between the exercise years and cerebrovascular reactivity.Results:The occurrence rate and slope of "w" wave in the study group were higher than those in the control group: 93.3%(28/30) vs. 86.7%(26/30), 2.27 ± 1.14 vs. 1.28 ± 0.23, 2.67 ± 0.63 vs. 1.41 ± 0.69, there were statistically significant ( P<0.05). The change rates of PI and RI before and after breath holding and ventilation in the study group were higher than those in the control group: 21.23 ± 7.67 vs. 13.89 ± 9.67, 14.62 ± 6.63 vs. 11.17 ± 1.78 and 26.26 ± 12.46 vs. 18.36 ± 12.13, 14.91 ± 4.91 vs. 10.83 ± 2.35, and the average cerebral blood flow velocity before and after ventilation was higher than that in the control group: (31.26 ± 4.92) cm/s vs. (24.89 ± 6.34) cm/s, there were statistically significant ( P<0.01). The exercise years of the study group was negatively correlated with the breath holding index. Conclusions:Moderate intensity exercise is associated with cerebral blood flow regulation in patients with mild carotid artery stenosis. Exercise years are negatively correlated with cerebral blood flow regulation. Impaired cerebral blood flow regulation may be one of the potential mechanisms of poor prognosis of stroke in carotid artery stenosis population.

The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.

The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.

The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.

The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.