Background Previous studies have found that exposure to benzo[a]pyrene (BaP) can lead to functional impairment of the human pancreas. Pancreatic and duodenal homeobox factor 1 (PDX-1) may play a role in regulating mitochondrial function. It is hypothesized that BaP exposure may interfere with PDX-1 expression in human pancreatic ductal epithelial cells (H6C7), thereby affecting mitochondrial transcription factor A (TFAM). This process could induce mitochondrial DNA (mtDNA) damage, disrupt pancreatic development and function, and elevate the risk of diabetes onset. Objective To investigate the mechanism of BaP-induced mtDNA damage through disruption of the PDX-1/TFAM pathway in a H6C7 cell model. Methods A H6C7 cell injury model was established using different concentrations of BaP. Cell viability was determined using cell counting kit-8 (CCK-8). After 24 h of BaP exposure (5,10, and 20 μmol·L⁻¹), cell morphological and mitochondrial membrane potential (MMP) changes were observed via confocalmicroscopy, and PDX-1/TFAM protein expression levels were assessed. Bioinformatics analysis combined with dual-luciferase reporter assays was used to confirm PDX-1 directly targeting the TFAM promoter. Following PDX-1 overexpression or silencing in BaP treated cells, flow cytometry was used to evaluate viability and apoptosis, while Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) measured PDX-1/TFAM expression and mitochondrial DNA copy number (mtDNA-cn). Results The cell injury model demonstrated that, compared with the control group, BaP exposure reduced cell viability, disrupted membrane integrity, induced nuclear fragmentation, and decreased MMP. Protein expression levels of PDX-1 and TFAM were significantly downregulated in the 10 and 20 μmol·L⁻¹ groups (P<0.05). Dual-luciferase reporter assays confirmed that PDX-1 overexpression upregulated TFAM levels. Flow cytometry revealed that PDX-1 overexpression significantly reduced apoptosis rate (P<0.001), whereas PDX-1 silencing increased apoptosis rate (P<0.001). Compared with the BaP-only group, BaP+PDX-1 overexpression elevated TFAM protein and mRNA expression as well as mtDNA-cn (P<0.01), while BaP+siRNA-PDX-1 suppressed these parameters (P<0.001). Conclusion BaP exposure promotes apoptosis in human pancreatic cells. PDX-1, a key gene in pancreatic development, regulates the expression of TFAM, a core regulator of mitochondrial function. This interaction triggers changes in MMP and mtDNA-cn, activates the PDX-1/TFAM/mtDNA axis, and ultimately leads to pancreatic cell injury.

Background Previous studies have found that exposure to benzo[a]pyrene (BaP) can lead to functional impairment of the human pancreas. Pancreatic and duodenal homeobox factor 1 (PDX-1) may play a role in regulating mitochondrial function. It is hypothesized that BaP exposure may interfere with PDX-1 expression in human pancreatic ductal epithelial cells (H6C7), thereby affecting mitochondrial transcription factor A (TFAM). This process could induce mitochondrial DNA (mtDNA) damage, disrupt pancreatic development and function, and elevate the risk of diabetes onset. Objective To investigate the mechanism of BaP-induced mtDNA damage through disruption of the PDX-1/TFAM pathway in a H6C7 cell model. Methods A H6C7 cell injury model was established using different concentrations of BaP. Cell viability was determined using cell counting kit-8 (CCK-8). After 24 h of BaP exposure (5,10, and 20 μmol·L⁻¹), cell morphological and mitochondrial membrane potential (MMP) changes were observed via confocalmicroscopy, and PDX-1/TFAM protein expression levels were assessed. Bioinformatics analysis combined with dual-luciferase reporter assays was used to confirm PDX-1 directly targeting the TFAM promoter. Following PDX-1 overexpression or silencing in BaP treated cells, flow cytometry was used to evaluate viability and apoptosis, while Western blot and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) measured PDX-1/TFAM expression and mitochondrial DNA copy number (mtDNA-cn). Results The cell injury model demonstrated that, compared with the control group, BaP exposure reduced cell viability, disrupted membrane integrity, induced nuclear fragmentation, and decreased MMP. Protein expression levels of PDX-1 and TFAM were significantly downregulated in the 10 and 20 μmol·L⁻¹ groups (P<0.05). Dual-luciferase reporter assays confirmed that PDX-1 overexpression upregulated TFAM levels. Flow cytometry revealed that PDX-1 overexpression significantly reduced apoptosis rate (P<0.001), whereas PDX-1 silencing increased apoptosis rate (P<0.001). Compared with the BaP-only group, BaP+PDX-1 overexpression elevated TFAM protein and mRNA expression as well as mtDNA-cn (P<0.01), while BaP+siRNA-PDX-1 suppressed these parameters (P<0.001). Conclusion BaP exposure promotes apoptosis in human pancreatic cells. PDX-1, a key gene in pancreatic development, regulates the expression of TFAM, a core regulator of mitochondrial function. This interaction triggers changes in MMP and mtDNA-cn, activates the PDX-1/TFAM/mtDNA axis, and ultimately leads to pancreatic cell injury.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Background: and Purpose This study aimed to investigate the association between residual inflammatory risk (RIR) and vulnerable plaques using high-resolution magnetic resonance imaging (HRMRI) in symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: This retrospective study included 70%–99% symptomatic ICAS patients hospitalized from January 2016 to December 2022. Patients were classified into four groups based on high-sensitivity C-reactive protein (hs-CRP) and low-density lipoprotein cholesterol (LDL-C): residual cholesterol inflammatory risk (RCIR, hs-CRP ≥3 mg/L and LDL-C ≥2.6 mmol/L), RIR (hs-CRP ≥3 mg/L and LDL-C <2.6 mmol/L), residual cholesterol risk (RCR, hs-CRP <3 mg/L and LDL-C ≥2.6 mmol/L), and no residual risk (NRR, hs-CRP <3 mg/L and LDL-C <2.6 mmol/L). Vulnerable plaque features on HRMRI included positive remodeling, diffuse distribution, intraplaque hemorrhage, and strong enhancement. Results: Among 336 included patients, 21, 60, 58, and 197 were assigned to the RCIR, RIR, RCR, and NRR groups, respectively. Patients with RCIR (adjusted odds ratio [aOR], 3.606; 95% confidence interval [CI], 1.346–9.662; P=0.011) and RIR (aOR, 3.361; 95% CI, 1.774–6.368, P<0.001) had higher risks of strong enhancement than those with NRR. Additionally, patients with RCIR (aOR, 2.965; 95% CI, 1.060–8.297; P=0.038) were more likely to have intraplaque hemorrhage compared with those with NRR. In the sensitivity analysis, RCR (aOR, 2.595; 95% CI, 1.201–5.608; P=0.015) exhibited an additional correlation with an increased risk of intraplaque hemorrhage. Conclusion In patients with symptomatic ICAS, RIR is associated with a higher risk of intraplaque hemorrhage and strong enhancement, indicating an increased vulnerability to atherosclerotic plaques.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Objective To propose a precise suctioning scheme for intravenous drug dispensing based on the vial dispensing robot to enhance the quality of finished infusion.Methods Six kinds of typical representative vial drugs were selected as the research objects,including pantoprazole sodium for injection,papaverine hydrochloride for injection,cefuroxime sodium for injection,Bozhi Glycopeptide Injection,Esomeprazole Sodium for Injection and Methylprednisolone Sodium Succinate for injection.The optimal suction speed was determined by studying the relationship between the size parameters of vials and the suction speed of robot dispensing,which was used to carry out drug dispensing with the vial dispensing robot to verify whether the minimum drug residue could be obtained with the speed.The drug residue was compared with that by manual dispensing.SPSS 24.0 and Excel 2021 were applied to statistical analysis.Results The optimal suction efficiency and minimized drug residue could be got with the depth of the syringe needle hole into the rubber plug(X)less than the height of the rubber plug(H)and the optimal suction speed(Vs)of 7.48 mm/s;the suction efficiency could be ensured without air drawn in when X not less than H and Vs ranging from 10.64 to 39.31 mm/s.The mean values of the drug residue by the robot were all lower than those by manual dispensing,with the differences being statistically significant(P<0.05).Conclusion The proposed scheme can be used for optimizing the parameters of the vial vial dispensing robot to obtain infusion solution with high stability and reliability,which promotes standardization and normalization of intravenous infusion dispensing process.[Chinese Medical Equipment Journal,2025,46(9):45-51]

Objective To explore the application value of CT-based radiomics in differentiating pneumonia-type mucinous adenocarcinoma(PTMA)from organizing pneumonia(OP).Methods A total of 52 PTMA patients and 102 OP patients were retrospectively included and randomly divided into training set(n=124)and test set(n=30)in an 8∶2 ratio.Eight PTMA patients and 22 OP patients from another hospital during the same period were included as external validation set(n=30).Clinical characteristics and CT signs of the patients were selected to construct the clinical model.Radiomics features were extracted and dimensionality reduction was performed through the least absolute shrinkage and selection operator(LASSO)algorithm.A radiomics model was constructed and the Radiomics score(Radscore)was calculated.The Radscore was combined with clinical factors to establish the combined model and a nomogram was illustrated.The models' fitting degree was analyzed by the calibration curve,while their efficacy was evaluated by the receiver operating characteristic(ROC)curve and decision curve analysis(DCA).Results The clinical model,established based on the border,cystic space and bronchial leafless tree sign,achieved area under the curve(AUC)of 0.850,0.782,and 0.759 in the training set,test set,and external validation set,respectively.Thirteen features were obtained to construct the radiomics model,with AUC of 0.925,0.865,and 0.830,respectively.The AUC of the combined model were 0.970,0.905,and 0.864,respectively,in which the calibration curve demonstrated good model fitting.DCA indicated that the combined model had the greatest clinical net benefit.Conclusion The combined model based on CT radiomics can effectively distinguish PTMA from OP.

To explore the application effect of host restriction factors(HRFs)in the development of antiviral gene drugs,this study based on the"common pathway of viral infection"and"host innate immunity HRFs",the genes of three antiviral HRFs,namely cholesterol-25-hydroxylase(CH25H),interferon-induced transmembrane protein(IFITM3)and interferon-stimulated gene 15(ISG15)were fused and expressed using pCK vectors to construct antiviral gene drugs.The fusion expression gene sequence CH25H-IFITM3-ISG15(C Ⅱ)was constructed by linking the gene cod-ing sequences of these three HRFs through the cleavage peptide coding sequence.Subsequently,the C Ⅱ sequence was amplified by PCR,ligated to the pCK expression vector,and the recombinant plasmid was transformed,identified,and extracted to obtain a candidate biodrug based on the DNA expression system,which was named pCK-CⅡ.Then,the recombinant plasmid was transfected in-to HEK 293T cells,and the expression of three antiviral proteins was successfully detected by Western blot.To clarify the antiviral effect of pCK-C Ⅱ at the cellular level,pCK-C Ⅱ was trans-fected into HEK 293 cells and BHK-21 cells,respectively.Twenty-four hours later,the BHK-21 cells were infected with vesicular stomatitis virus expressing green fluorescent protein(VSV-GFP),12 h later,the cells were observed under a fluorescence microscope and detected by flow cy-tometry;HEK 293 cells were inoculated with H3N2 subtype influenza virus,and the expression of H3N2 subtype influenza virus nuclear proteins was detected after 12 h using Western blot.The re-sults showed that transient transfection of pCK-C Ⅱ plasmid could significantly reduce the fluores-cence level of cells and the expression of nuclear protein of H3N2 subtype influenza virus in infec-ted cells.These results indicated that pCK-C Ⅱ had an inhibitory effect on the infection of VSV-GFP and H3N2 subtypes of influenza viruses after transient transfection of cells.

Transmembrane proteins (TMEM) are a type of membrane protein. Most proteins in this family are located in the phospholipid bilayer of the cell membrane, while a smaller portion is found in the membranes of cellular organelles. Transmembrane protein 43 (TMEM43) is a member of the TMEM protein family and is encoded by the TMEM43 gene. This protein consists of 400 amino acids and has 4 transmembrane domains and 1 membrane-associated domain. TMEM43 is localized to various biological membranes within the cell, such as the cell membrane and nuclear membrane, where it forms transmembrane channels for various ions. Additionally, TMEM43 is expressed in many species, showing high genetic similarity, especially with the four transmembrane domains being highly conserved. Current studies on the TMEM43 gene are still in its early stages, mainly focusing on its association with arrhythmogenic right ventricular cardiomyopathy (ARVC) and cancer. However, recent studies suggest that pathogenic mutations in TMEM43 may cause auditory neuropathy spectrum disorder (ANSD). Patients with TMEM43 p.Ser372Ter exhibited late-onset progressive ANSD. Impact of TMEM43 pathogenic mutations on individual hearing was likely mediated through effects on gap junction (GJ) structures on glia-like supporting cells (GLS), cell membranes. The TMEM43 p.Arg372Ter pathogenic mutation primarily affected the structure and function of TMEM43 protein, leading to premature termination of protein translation and the production of a truncated protein. Abnormal TMEM43 protein significantly reduced K⁺ influx in GLS cells, disrupting the endolymphatic K⁺ circulation and cochlear microenvironment homeostasis. When K⁺ circulation was obstructed, the endocochlear potential (EP) became abnormal, impairing the physiological function of hair cells and potentially leading to hearing impairment. However, it is important to note that studies on the mechanism is limited, and more experimental evidence is needed to confirm this hypothesis. Currently, there is a significant gap in research on TMEM43 and hearing loss, with many issues remaining unresolved. While TMEM43 has been studied in relation to hearing loss in humans, zebrafish, mice, and rats, the research is still preliminary. Detailed investigations into the molecular pathogenic mechanisms, the impact of mutations on hearing damage, and related therapeutic strategies are needed. Additionally, as a newly identified hearing loss-related gene, the mutation frequency and incidence of hearing disorders associated with TMEM43 have not been effectively quantified. For example, the ClinVar database listed 829 mutation sites for the TMEM43 gene, with only three mutations related to auditory neuropathy: c.605A>T (p.Asn202Ile), c.889T>A (p.Phe297Ile), and c.1114C>T (p.Arg372Ter). Aside from the aforementioned TMEM43 c.1114C>T (p.Arg372Ter) mutation observed in patients, the other two mutations were experimentally induced and have not been found in patients. Consequently, these mutations have been classified as unknown significance. We reviewed the current understanding of TMEM43 and hearing loss, analyzed its role in ear development and sound conduction, and explored the impact of TMEM43 gene variations on hearing loss, aiming to provide new insights for future research and precision medicine related to TMEM43.