Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

To address communication interference in complex noise environments inside and outside helmets,this study aims to improve the acoustic communication quality of in-helmet systems.A four-element microphone array communication hardware system was designed and implemented for use within the confined space of a helmet.Based on simulations of the internal acoustic field,the system incorporates a set of signal processing techniques,including array beamforming,echo cancellation,stationary noise speech enhancement,non-stationary noise suppression,and automatic gain control,forming a complete voice signal processing framework.Experimental results show that the proposed in-helmet microphone array noise reduction system achieves favorable downlink voice clarity under a total noise level of 85 dB(A),preliminarily validating the effectiveness and applicability of the implemented algorithms.This research provides essential technical and theoretical support for the future design and development of open-form in-helmet communication systems.

During long-term extravehicular activities(EVA),there have been multiple instances of localized discomfort due to cold extremities such as hands and feet.The primary reason is that the design of space suit gloves prioritizes maximizing operational flexibility,which leads to reduced passive thermal protection in certain areas.Insufficient local thermal protection can cause the hands to lose metabolic heat in cold environments over time,resulting in cold stress.Therefore,it is necessary to conduct research on temperature control technology to meet the thermal comfort requirements of astronauts' hands during EVA.Effective active temperature measures can expand the range of low temperature working environments that astronauts' hands can adapt to during EVA,enhance hand thermal comfort,and ensure hand operational capabilities,preventing excessive cold from exceeding medical requirement and affecting extravehicular missions.This paper combines the metabolic heat generation patterns of the human hand to analyze the temperature control requirements for extravehicular gloves,simulate and optimize the layout of electric heaters,and evaluate the feasibility of the electric heating system for extravehicular gloves by building a thermal simulation model.Through prototype vacuum thermal testing,comprehensive verification of the temperature control module for extravehicular gloves was achieved,demonstrating the effectiveness of the temperature control system.

Objective To investigate the direct stimulatory effects of calprotectin S100A8/A9 on hepatic stellate cells(HSCs)and underlying regulatory mechanisms.Methods Primary HSCs of mice were stimulated with S100A8/A9 heterodimer recombinant protein at 200 and 1000 ng/mL.Data on quantitative proteomics was obtained using the tandem mass tag(TMT)-labeled method before changes in the protein level of HSCs were analyzed.Differentially expressed proteins(DEPs)were screened using Significance B method and P＜0.05,followed by Reactome pathway enrichment analysis.Furthermore,protein-protein interactions between the DEPs enriched in the pathways were analyzed using the STRING database.Results The protein expression profile of HSCs was significantly altered after treatment with S100A8/A9 at 1000 ng/mL.Reactome pathway enrichment analysis revealed significant enrichment in such pathways as transforming growth factor-beta(TGF-β)signaling,nuclear factor kappa-B(NF-κB)signaling activation,cytokine-mediated immune regulation,and collagen biosynthesis.The analysis of protein-protein interactions identified NF-kappa-B transcription factor subunit(RELB),chemokine(C-X-C motif)ligand 10(CXCL10)and Notch receptor 1(NOTCH1)as key hub proteins in the regulatory network.Conclusion S100A8/A9 can directly stimulate the activation of HSCs,through NF-κB signaling,TGF-β signaling,and Notch signaling pathways potentially.This study sheds light on the mechanisms underlying the activation of HSCs stimulated by S100A8/A9.

Macrophages are the key cells in the process of hepatic fibrosis. Therefore, they promote the progression and regression of liver fibrosis by participating in all stages. The treatment of liver fibrosis is significantly identified by the main subtypes of intrahepatic macrophages. This article summarizes the types and functions of macrophages according to the inflammatory phenotype, origin, and surface markers and their effect on fibrosis; introduces the new subtypes and mode of action in the occurrence and development of hepatic fibrosis, as revealed by the single-cell sequencing technique; and analyzes the limitations of traditional antifibrotic therapy and the advantages of macrophage-targeting therapeutics, which could indicate the new direction for the study of new macrophage subtypes in hepatic fibrosis.

OBJECTIVE To study the effects of ethanol on markers of gastric stem cells and epithe-lial cells,and explore the related signal pathways for stem cells differentiation in a mouse gastric mucous injury model.METHODS Male C57BL/6 mice were randomly divided into normal control and ethanol groups.The mice in the control group were given normal drinking water while those in the ethanol group were gavaged with 10 ml·kg-1 50%(V/V)ethanol on day 1,and drinking water containing 10%(V/V)ethanol was given on day 2-9.On the 10th day,stomach tissues were collected.HE staining was used to detect pathological changes in the stomach.Immunohistochemistry(IHC)staining was used to detect changes of such cell markers as mucin 5AC,H+/K+ATPase β and pepsin C.Immunofluorescence(IF)staining was employed to analyze changes in expression of cell markers such as H+/K+ATPase β,pepsin C and gastrin.ELISA assay was used to measure gastrin,somatostatin and interleukin 1β(IL-1β)concentrations in gastric tissue homogenates.Flow cytometry was adopted to measure the number of leucine rich repeat containing G protein-coupled receptor 5 positive(LGR5+)stem cells in gastric glands.Organoids was constructed to characterize stem cell activity.RNA sequencing and bioinformatics analysis were conducted to analyze the inflammatory pathways and differentiation signaling pathways during mice gastric mucous injury.RESULTS H&E results showed multifocal necrosis of the mucosal layer appeared in the ethanol group,accompanied by pyknosis,lysis and detachment of mucosal epithelial cells and gastric gland cells.IHC results showed decreased expressions of mucin 5AC and increased expressions of H+/K+ATPase β and pepsin C.IF results revealed increased expressions of H+/K+ATPase β,pepsin C,and gastrin after ethanol treatment.ELISA results demonstrated significant increases in gastrin,somatostatin and IL-1β levels in gastric tissues of the ethanol group.Flow assay results suggested that the number of LGR5+stem cells significantly decreased in ethanol treated gastric tissues.Stem cells from stomach tissues treated with ethanol did not grow into organoids.RNA sequencing and bioinformatics analyses revealed enrichment of TNF,NF-κB and Notch pathways in the ethanol group.CONCLUSION Administration of 50%ethanol solution on day 1,followed by continuous admin-istration of 10%ethanol solution on day 2-9 can induce histopathological injury to the gastric gland and stem cells,and an increase in epithelial cells.These changes may be related to the up-regulation of inflammatory pathways and Notch signaling pathways triggered by ethanol.

OBJECTIVE To study the effects of ethanol on markers of gastric stem cells and epithe-lial cells,and explore the related signal pathways for stem cells differentiation in a mouse gastric mucous injury model.METHODS Male C57BL/6 mice were randomly divided into normal control and ethanol groups.The mice in the control group were given normal drinking water while those in the ethanol group were gavaged with 10 ml·kg-1 50%(V/V)ethanol on day 1,and drinking water containing 10%(V/V)ethanol was given on day 2-9.On the 10th day,stomach tissues were collected.HE staining was used to detect pathological changes in the stomach.Immunohistochemistry(IHC)staining was used to detect changes of such cell markers as mucin 5AC,H+/K+ATPase β and pepsin C.Immunofluorescence(IF)staining was employed to analyze changes in expression of cell markers such as H+/K+ATPase β,pepsin C and gastrin.ELISA assay was used to measure gastrin,somatostatin and interleukin 1β(IL-1β)concentrations in gastric tissue homogenates.Flow cytometry was adopted to measure the number of leucine rich repeat containing G protein-coupled receptor 5 positive(LGR5+)stem cells in gastric glands.Organoids was constructed to characterize stem cell activity.RNA sequencing and bioinformatics analysis were conducted to analyze the inflammatory pathways and differentiation signaling pathways during mice gastric mucous injury.RESULTS H&E results showed multifocal necrosis of the mucosal layer appeared in the ethanol group,accompanied by pyknosis,lysis and detachment of mucosal epithelial cells and gastric gland cells.IHC results showed decreased expressions of mucin 5AC and increased expressions of H+/K+ATPase β and pepsin C.IF results revealed increased expressions of H+/K+ATPase β,pepsin C,and gastrin after ethanol treatment.ELISA results demonstrated significant increases in gastrin,somatostatin and IL-1β levels in gastric tissues of the ethanol group.Flow assay results suggested that the number of LGR5+stem cells significantly decreased in ethanol treated gastric tissues.Stem cells from stomach tissues treated with ethanol did not grow into organoids.RNA sequencing and bioinformatics analyses revealed enrichment of TNF,NF-κB and Notch pathways in the ethanol group.CONCLUSION Administration of 50%ethanol solution on day 1,followed by continuous admin-istration of 10%ethanol solution on day 2-9 can induce histopathological injury to the gastric gland and stem cells,and an increase in epithelial cells.These changes may be related to the up-regulation of inflammatory pathways and Notch signaling pathways triggered by ethanol.

Macrophages are the key cells in the process of hepatic fibrosis. Therefore, they promote the progression and regression of liver fibrosis by participating in all stages. The treatment of liver fibrosis is significantly identified by the main subtypes of intrahepatic macrophages. This article summarizes the types and functions of macrophages according to the inflammatory phenotype, origin, and surface markers and their effect on fibrosis; introduces the new subtypes and mode of action in the occurrence and development of hepatic fibrosis, as revealed by the single-cell sequencing technique; and analyzes the limitations of traditional antifibrotic therapy and the advantages of macrophage-targeting therapeutics, which could indicate the new direction for the study of new macrophage subtypes in hepatic fibrosis.

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM_2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM_2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM_2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM_2.5 group, and an SAL+PM_2.5 group, each containing 10 mice. In the SAL group and the SAL+PM_2.5 group, the mice were administered SAL (60 mg·kg⁻¹) by gavage, while in the control group and the PM_2.5 group, sterile saline (10 mL·kg⁻¹) was administered by gavage. In the PM_2.5 group and the SAL+PM_2.5 group, PM_2.5 suspension (8 mg·kg⁻¹) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg⁻¹) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM_2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM_2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM_2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM_2.5 group showed increased Shannon index compared to the PM_2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM_2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM_2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM_2.5 group, and finally, the three groups clustered with the PM_2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM_2.5 group were significantly decreased. Compared to the control group, the PM_2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM_2.5 group, the SAL+PM_2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM_2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM_2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM_2.5 group (P<0.05). Conclusion Exposure to PM_2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Objective To observe the effectiveness of plasma exchange(PE)combined with the double plasma molecular adsorption system(DPMAS)in managing liver failure complicated by severe hyperbilirubinemia.Methods A total of 120 patients with liver failure who received artificial liver therapy were selected in Mianyang Central Hospital from June 2023 to June 2024 were as study objects.These patients were divided into an observation group and a control group,with 60 cases in each group.The control group received standard medical treatment,while the observation group underwent PE+DPMAS therapy in addition to the standard regimen,concrete method:firstly,low molecular weight heparin sodium at 25000 U was added to the 0.9%physiological saline(NS)1 750 mL pre flushing tube;Secondly,low molecular weight heparin sodium at 12 500 U and 0.9%NS at 500 mL were administered,and finally 0.9%NS 500 mL was used for flushing pipes,based on the patient's coagulation function,low molecular weight heparin sodium at 12500 U and 0.9%NS at 500 mL can be sequentially moved forward,after the pre flushing was completed,it can be connected to the catheter and wait for it to be loaded onto the machine.The circulating flow rate for the first 30 minutes after starting the machine was 1 800-2000 mL/h,with a flow rate of 125-140 mL per minute,blood is drawn out from the arterial terminals and separated by a plasma separator,the separated plasma was adsorbed by a series of AR-350 bilirubin columns and YTS-200 hemoperfusion apparatus before flowing into the venous circuit tube and returning to the body.The differences of clinical symptoms and laboratory indicators,including liver function indicators[aspartate transaminase(AST),alanine transaminase(ALT),alkaline phosphatase(ALP),γ-glutamyl transferase(GGT),total bile acid(TBA),total bilirubin(TBil),direct bilirubin(DBil),albumin(ALB)],kidney function indicators[creatinine(Cr)],coagulation function indicators[prothrombin time(PT)and prothrombin activity(PTA)]before and after treatment between the two groups were compared,and clinical efficacy and adverse reactions of the two groups were observed.Results Following treatment,both groups exhibited significant reductions in AST,ALT,ALP,TBA,TBil,and DBil levels compared to before treatment,the levels of total AST,ALT,TBA and TBil after treatment in the observation group were significantly lower than those in the control group[AST(U/L):84.2±69.3 vs.158.3±130.2,ALT(U/L):119.3±112.1 vs.145.9±124.7,TBA(μmol/L):59.1±48.3 vs.158.3±130.2,TBil(μmol/L):101.3±56.4 vs 145.9±124.7,all P<0.05];ALB increased significantly in the both groups after treatment compared to before treatment(g/L:the observation group was 35.1±3.7 vs.32.1±4.6,the control group was 33.1±3.1 vs.31.8±3.5,both P<0.05),however,there was no significantly difference between the two groups(P>0.05).In the observation group,PT shortened significantly after treatment(s:13.6±1.4 vs.14.5±2.1,P<0.05),while PTA increased significantly after treatment[(95.1±19.5)%vs.(83.2±21.1)%,P<0.05];moreover,the time required to achieve 30%,50%,and 70%reductions in TBil was markedly shorter in the observation group than in the control group[time required to achieve 30%reductions in TBil(days):6.1±4.3 vs.9.7±4.8,time required to achieve 50%reductions in TBil(days):9.3±5.1 vs.11.9±6.2,time required to achieve 70%reductions in TBil(days):13.2±5.9 vs.18.1±6.9,all P<0.05].The total effective rate of observation group was significantly higher than that of control group[93.3%(56/60)vs.68.3%(41/60),P<0.05].Both groups completed the treatment without deaths.During the treatment,5 cases experienced allergic reactions and 3 cases experienced a decrease in blood pressure,after symptomatic treatment,all patients continued to complete the treatment.Conclusion PE combined with DPMAS shows considerable clinical benefits for patients with liver failure and severe hyperbilirubinemia by effectively lowering bilirubin levels and accelerating recovery,thus shortening the disease course.