Objective:To develop fluorescent nanoprobes with aggregation-induced emission characteristics and to systematically evaluate their optical properties, biosafety, anti-tumor activity, and imaging capability, thereby assessing their potential for early precision diagnosis and treatment of oral cancer in mice.Methods:Control probes (PEG@TPD) were prepared by encapsulating ( E)-4-(2-(4′-(1-phenyl-2,2-bis(4-methoxyphenyl)vinyl)biphenyl-4-yl)vinyl)-4-(dicyanomethylene)-4 H-chromene (TPD) using 1,2-distearoyl- SN-glycerol-3-phosphoethanolamine- N-polyethylene glycol 2000-maleimide as the carrier. Fluorescent nanoprobes (GE11-PEG@TPD) were subsequently fabricated by surface modification with the targeting GE11 peptide. The morphology and particle size of the nanoprobes were characterized by transmission electron microscopy and dynamic light scattering. The optical properties of the nanoprobes were analyzed using ultraviolet-visible spectrophotometry and fluorescence spectrophotometry. Mouse squamous carcinoma SCC-7 cells were randomly divided into six groups by the random number table method. The PBS, PEG@TPD, and GE11-PEG@TPD groups were not treated with light, while the PBS+L, PEG@TPD+L, and GE11-PEG@TPD+L groups were exposed to white light (25 W/cm 2, 10 min) at a nanoprobe concentration of 20 μg/ml (based on TPD concentration). Cell survival rate was assessed by the cell counting kit-8 assay. Cellular uptake, intracellular reactive oxygen species levels, and cytotoxicity were evaluated using laser scanning confocal microscopy. The apoptosis rate was evaluated by cell apoptosis assay. Twelve 6-week-old female C3H/HeN mice were randomly divided into two groups: PEG@TPD-1 group and GE11-PEG@TPD-1 group, with 6 mice in each group. Subcutaneous oral cancer models were established by injecting SCC-7 cell suspensions into the dorsal region of mice in two groups. Each mouse was intravenously administered 200 μl of PEG@TPD or GE11-PEG@TPD solution (1 mg/ml, based on TPD concentration). Tumor boundaries and scope were visualized using a small animal in vivo imaging system. At the optimal imaging time point, three mice from each group were euthanized, and major organs and tumor tissues were collected to measure probe accumulation. Statistical comparisons between two groups were performed using independent samples t-tests, while one-way or two-way analysis of variance was applied for multiple group comparisons. Results:Both PEG@TPD and GE11-PEG@TPD exhibited a relatively regular sphere, with average particle sizes of (92.76±8.80 and 117.50±6.40) nm, respectively. PEG@TPD showed two obvious absorption peaks at 352 and 444 nm. GE11 peptide showed a polypeptide characteristic absorption peak at 280 nm, GE11-PEG@TPD showed three characteristic absorption peaks at 280, 352 and 444 nm. Under dark conditions, cell survival rate remained above 80% even at a concentration of 160 μg/ml. After light irradiation, cell survival rate in the PEG@TPD+L group at 20 and 40 μg/ml [(68.2±5.2)% and (48.6±7.1)%] were higher than those in the GE11-PEG@TPD+L group [(55.0±2.8)% and (30.0±9.2)%], with statistically significant differences ( P<0.05, 0.01). At incubation time points of 2, 4, and 6 h, the relative fluorescence intensity of the GE11-PEG@TPD group (119.4±10.2, 192.9±14.2, and 234.1±4.8) were higher than those of the PEG@TPD group (98.6±7.5, 163.8±3.1, 204.6±11.2), with statistically significant differences (all P<0.05). The relative fluorescence intensity of the PEG@TPD+L and GE11-PEG@TPD+L group (68.5±4.7 and 86.8±10.0) were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups (6.1±8.0, 7.6±1.8, 4.7±4.2 and 21.1±7.6), with statistically significant differences (all P<0.01). And the difference between the GE11-PEG@TPD+L and PEG@TPD+L groups was also statistically significant ( P<0.05). Viable cell proportions in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups all exceeded 95.0%, while those in the PEG@TPD+L and GE11-PEG@TPD+L groups decreased to (11.1±3.7)% and (4.3±1.1)%, respectively, with a statistically significant difference between them ( P<0.05). The apoptotic cell proportions in the PEG@TPD+L and GE11-PEG@TPD+L groups [(40.5±4.3)% and (55.3±7.4)%] were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups [(27.3±2.0)%, (28.2±1.9)%, (28.6±1.2)%, and (29.7±3.0)%], with statistically significant differences ( P<0.05, 0.01). Moreover, the difference between the GE11-PEG@TPD+L and the PEG@TPD+L groups was also statistically significant ( P<0.01). The mean fluorescence intensities of the GE11-PEG@TPD-1 group at 1, 3, 5, 8, and 24 h, as well as in ex vivo tumor tissues[(5.2±0.8, 5.9±0.7, 6.6±1.0, 7.9±0.6, 7.8±0.7 and 20.6±3.5)×10 6 p/s/cm 2/sr] were all higher than those in the PEG@TPD-1 group [(3.2±0.7, 4.2±0.7, 4.6±0.9, 5.1±0.9, 4.7±0.9 and 14.2±1.8)×10 6 p/s/cm 2/sr], with statistically significant differences ( P<0.05, 0.01). Conclusions:The fluorescent nanoprobes exhibit uniform particle size, high photostability, and good biocompatibility. They demonstrate significant tumor-killing effects at the cellular level and possess tumor-targeting capability in vivo, showing promising application potential for the early precision diagnosis and treatment of oral cancer.

Oxygen generation technologies with lower requirement and higher performance urgently need to be developed to meet the challenges of manned lunar landing and Mars exploration.In this paper,the mission requirements,technical characteristics,key technologies and operation status of oxygen generation assembly by water electrolysis(OGAWE)in China Space Station(CSS)are introduced.Furthermore,the latest developments about oxygen generation by electrolyzing carbon dioxide based on solid oxide electroyte is reported.The application effects and research achievements demonstrate the oxygen generation by electrolysis is one of the most suitable techniques for oxygen regeneration in manned space mission.In addition,the oxygen generation by novel electrolysis technology provides feasible approach for improving the performance of oxygen regeneration and producing oxygen by in-situ utilization of extraterrestrial resource.These development experiments of OGAWE in CSS and research results of novel electrolysis provide valuable references for the technical progress of oxygen generation by electrolysis for manned spaceflight.

Objective:To evaluate the effect of digital design combined with 3D printing technology in the repair of mandibular defects with fibular myocutaneous flap.Methods:From July 2017 to August 2022, 25 patients with mandibular defects repaired by fibular musculocutaneous flap after oral tumor surgery were retrospectively analyzed. The cohort consisted of 25 patients (16 male, 9 female) aged 19-68 (42.5±5.3) years. The patients were divided into two groups according to different fibula shaping methods: Study group (11 cases): digital design combined with 3D printing technology was used for fibula shaping; Control group (14 cases): conventional fibula shaping was performed based on the surgeon's experience.Results:The fibula shaping time in the study group was (51.2±4.2) min, which was shorter than that in the control group (79.1±8.0) min ( P<0.001). The study group showed higher satisfaction scores for facial appearance compared to the control group [(8.3±0.8) vs (6.9±0.6) points, P<0.001]. The survival rates were 11/11 in the study group and 13/14 in the control group, with a significantly higher survival rate observed in the study group ( P<0.001). At 3 months postoperatively, the mouth opening measurements were (3.5±0.2) cm in the study group and (3.5±0.1) cm in the control group, showed no statistically significant difference ( P=0.334). Conclusion:The application of digital design combined with 3D printing technology in fibula musculocutaneous flap reconstruction of mandibular defects reduces fibula shaping time, improves flap survival rates, and yields higher patient satisfaction with facial aesthetics.

BACKGROUND:H uman pluripotent stem cell-derived cardiomyocytes offer an ideal cellular resource for studying heart diseases,conducting drug screening,developing in vitro heart models,and exploring potential cell therapies.However,human pluripotent stem cell-derived cardiomyocytes are characterized by immaturity with limited specific gene expression,low Ca2+processing levels,and underdeveloped structural,metabolic,and electrophysiological features.These limitations significantly impede the application of human pluripotent stem cell-derived cardiomyocytes.OBJECTIVE:To review the academic progress and clinical application of promoting the maturation of human pluripotent stem cell-derived cardiomyocytes by in vitro synthetic microenvironment.METHODS:CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases were searched,with"human pluripotent stem cells,human myocardial cells,hPSC-CMs,mature,OA,human pluripotent stem cell-derived cardiomyocytes,hPSC-CMs"as English search terms and"human pluripotent stem cells,cardiomyocytes,mature,OA,hPSC-CMs"as Chinese search terms.All relevant literature published from January 2002 to July 2024 was retrieved and 82 articles were included in the review.RESULTS AND CONCLUSION:(1)In recent years,in vitro synthetic microenvironments have attracted extensive attention due to their excellent intrinsic properties such as stiffness,plasticity,nanoscale morphology,and chemical functionality.(2)Human pluripotent stem cell-derived cardiomyocytes can be used as an effective platform for the treatment of cardiovascular diseases.(3)Mechanical stimulation,electrical stimulation,addition of biochemical molecules,and three-dimensional culture methods are effective methods to promote the maturation of human pluripotent stem cell-derived cardiomyocytes,which can further promote the clinical application of human pluripotent stem cell-derived cardiomyocytes.

Objective·To explore the mechanism at the atomic level by which the KRASG12D/R68G mutation induces tumor cell resistance to MRTX1133.Methods·The crystal structure data of the KRASG12D-MRTX1133 complex were obtained from the RCSB Protein Data Bank(PDB).PyMOL software was used to mutate arginine at position 68 of KRAS to glycine(R68G),constructing the initial conformations of the KRASG12D-MRTX1133 and KRASG12D/R68G-MRTX1133 complexes.The LEaP module was used to build simulation systems under periodic boundary conditions.The ff19SB force field was applied to standard amino acids in KRAS,GAFF(general AMBER force field)to MRTX1133,and TIP3P(intermolecular potential three point)to water molecules.Energy minimization was performed using the Amber software suite.The systems were then heated to 300 K,followed by NVT(constant volume and temperature)equilibration and NPT(constant pressure and temperature)production.Root mean square deviation(RMSD),root mean square fluctuation(RMSF),principal component analysis(PCA)and solvent-accessible surface area(SASA)of MRTX1133 and GDP were analyzed using cpptraj.The number of hydrogen bonds between regions and the dynamic cross-correlation matrix(DCCM)of amino acid movements were also calculated.Results·RMSD analysis showed greater structural variation in KRAS in the KRASG12D/R68G system compared to the KRASG12D system.RMSF analysis revealed significantly higher fluctuations in the Switch Ⅰ and Switch Ⅱ regions of the KRASG12D/R68G system.PCA indicated that Switch Ⅰ and Switch Ⅱ in the KRASG12D/R68G system were more frequently in an open conformation.The distances between Switch Ⅰ and the P-loop,and between Switch Ⅱ and the P-loop,were larger in the KRASG12D/R68G system,indicating an expanded binding pocket for GDP and MRTX1133 compared to the KRASG12D system.SASA analysis indicated that both GDP and MRTX1133 had increased solvent exposure in the KRASG12D/R68G system.DCCM analysis revealed more decoupled movements among the Switch Ⅰ,Switch Ⅱ and P-loop regions in the KRASG12D/R68G system.Conclusion·The KRASG12D/R68G mutation disrupts the interactions between the Switch Ⅰ and Switch Ⅱregions,leading to their separation and the opening of the MRTX1133 binding pocket.This increases the solvent exposure of MRTX1133,accelerates its dissociation,and ultimately results in KRASG12D/R68G resistance to MRTX1133.

Objective To explore the mechanism by which gentiopicroside (GPS) prevents macrophage-mediated hepatic fibrosis by regulating the macrophage migration inhibitory factor (MIF)-secreted phosphoprotein 1 (SPP1) signaling pathway in hepatic stellate cells. Methods LX-2 cells were divided into control group, transforming growth factor β(TGF-β) group, and TGF-β combined with GPS (25, 50, 100, 150 μmol/mL) groups. Cell proliferation was detected by EDU assay, cell invasion was assessed by Transwell^TM assay, and the protein expressions of α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) were measured by Western blot. M1-type macrophage-conditioned medium (M1-CM) was used to treat LX-2 cells in the TGF-β group and TGF-β combined with GPS group. The concentrations of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) in the cell supernatant, as well as cell proliferation, invasion ability, and the expressions of α-SMA and COL1A1 were detected. Bioinformatics analysis was performed to identify the target intersections of GPS, hepatic fibrosis, and macrophage-related genes. Drug affinity responsive target stability (DARTS) experiments and Western blot were used to verify the regulatory effect of GPS on MIF. Furthermore, LX-2 cells were divided into control group, TGF-β group, TGF-β combined with M2-CM group, TGF-β and oe-NC combined with M2-CM group, and TGF-β and oe-MIF combined with M2-CM group to analyze the concentrations of iNOS and Arg1 in the cell supernatant, as well as changes in cell proliferation, invasion, and the expressions of α-SMA and COL1A1. LX-2 cells were also divided into control group, TGF-β group, TGF-β combined with oe-NC group, TGF-β combined with oe-MIF group, and TGF-β and oe-MIF combined with GPS group to determine the protein expressions of MIF and SPP1 by Western blot. A rat model of hepatic fibrosis was constructed to explore the potential therapeutic effects of GPS on hepatic fibrosis in vivo. Results Compared with the control group, the proliferation and invasion abilities of LX-2 cells in the TGF-β group were increased, and the protein expressions of α-SMA and COL1A1 were enhanced. GPS intervention inhibited the proliferation and invasion of LX-2 cells under TGF-β conditions and reduced the expressions of α-SMA and COL1A1. Compared with the control group, the concentration of iNOS in the cell supernatant of the TGF-β group was upregulated, while the concentration of Arg1 was decreased. M1-CM treatment further increased the concentration of iNOS, decreased the concentration of Arg1, and promoted cell proliferation and invasion, as well as upregulated the expressions of α-SMA and COL1A1 on the basis of TGF-β intervention. However, GPS could reverse the effects of M1-CM intervention. Bioinformatics analysis revealed that MIF was one of the target intersections of GPS, hepatic fibrosis, and macrophage-related genes, and GPS could target and inhibit its expression. Compared with the TGF-β group, after M2-CM intervention, the concentration of iNOS in the cell supernatant decreased, the concentration of Arg1 increased, the proliferation and invasion abilities of LX-2 cells were reduced, and the expressions of α-SMA and COL1A1 were weakened. However, overexpression of MIF reversed the effects of M2-CM intervention. Western blot results showed that compared with the control group, the protein expressions of MIF and SPP1 were enhanced in the TGF-β group. Overexpression of MIF further enhanced the expressions of MIF and SPP1, while GPS intervention inhibited the expressions of MIF and SPP1. In the animal experiment, GPS intervention treatment alleviated liver injury in rats with hepatic fibrosis and inhibited the expressions of MIF and SPP1, as well as α-SMA and COL1A1 in liver tissue. Conclusion GPS may prevent macrophage-mediated hepatic fibrosis by inhibiting the MIF-SPP1 signaling pathway in hepatic stellate cells.
Hepatic Stellate Cells/metabolism* ; Signal Transduction/drug effects* ; Macrophage Migration-Inhibitory Factors/genetics* ; Liver Cirrhosis/prevention & control* ; Macrophages/drug effects* ; Iridoid Glucosides/pharmacology* ; Humans ; Cell Proliferation/drug effects* ; Animals ; Cell Line ; Collagen Type I/metabolism* ; Collagen Type I, alpha 1 Chain ; Intramolecular Oxidoreductases/genetics* ; Rats ; Transforming Growth Factor beta/pharmacology* ; Actins/metabolism*

Objective:To analyze the effects of the disease and injury spectrum on health-adjusted life expectancy (HALE) among permanent residents aged 55 and above in Shenzhen from 2016 to 2030.Methods:Based on the mortality surveillance data and the permanent resident population data in Shenzhen from 2016 to 2022, the Sullivan method was used to calculate the HALE during 2016—2022. The Bayesian age-period-cohort model and the grey system model were used to predict the HALE during 2023—2030. The HALE changes in the two periods were decomposed into the contributions of 20 categories of diseases and injuries, respectively.Results:From 2016 to 2022, the HALE increased from 31.41 years (95% CI: 30.50-32.32) to 33.57 years (95% CI: 32.47-34.67). During this period, the mortality effect of neurological disorders slowed the increase of HALE, with a reduction of 0.27 years. By 2030, it is anticipated that the HALE will reach 36.40 years (95% CI: 34.78-38.01). This is expected to be influenced by the mortality effects of nutritional deficiencies (-0.40 years) and mental disorders (-0.29 years), as well as the disability effects of musculoskeletal disorders (-0.66 years), skin and subcutaneous diseases (-0.21 years) and nutritional deficiencies (-0.13 years). Conclusion:The HALE of permanent residents aged 55 years and above in Shenzhen demonstrated an increasing trend over time. Greater attention should be paid to the adverse effects of neurological disorders, nutritional deficiencies, mental disorders, musculoskeletal disorders, and skin and subcutaneous diseases on the continuous increase of HALE in this population.

Thoracic anesthesia with spontaneous respiration represents a form of precision anesthesia meticulously customized to individual patients.Considering the more stringent requirements this anesthesia approach imposes on the regulation of respiratory function,the writing group of the"Consensus of Experts on the Management of Thoracic Anesthesia with Spontaneous Respiration"has formulated elaborate guidelines regarding indications and contraindications,preoperative evaluation,anesthesia implementation,common complications,and treatment strategies.This was accomplished by referencing relevant domestic and international literature and integrating it with actual clinical requirements.The objective is to standardize the rational application of this anesthesia method.

Objective·To develop a graph neural network(GNN)-based auxiliary diagnostic model for gallbladder cancer on CT images,and validate its accuracy and feasibility.Methods·From January 2010 to November 2023,1 774 contrast-enhanced CT arterial-phase images were acquired from 887 patients with normal gallbladder,benign gallbladder disease,or gallbladder cancer at Xinhua Hospital and Renji Hospital,Shanghai Jiao Tong University School of Medicine.These images were randomly divided into training and testing sets at a 4∶1 ratio to develop a hybrid GNN-convolutional neural network(CNN)model,named VJK-GIN.The model constructed a pixel-level graph in which each pixel served as a node,and spatial adjacency defined the edges,enabling extraction of local texture features.In the model architecture design,VJK-GIN integrated a three-layer graph isomorphism network,augmented with virtual nodes and jump-knowledge connections;global pooling compressed node features into a graph-level representation,which was classified by a multi-layer perceptron head.Five-fold cross-validation was used to compare VJK-GIN with GNN baselines(GCN,GraphSAGE,GAT,and GIN)and CNN baselines(ViT,EfficientNetV2,and ConvNeXt)in terms of accuracy,precision,recall,F1-score,and area under the receiver operating characteristic curve(AUC).Results·The results of five-fold cross-validation showed that VJK-GIN achieved an F1-score of 0.799(95%CI 0.775?0.823),recall of 0.795(95%CI 0.773?0.817),precision of 0.799(95%CI 0.775?0.823),AUC of 0.812(95%CI 0.792?0.832),and accuracy of 0.773(95%CI 0.748?0.798),surpassing all competing models across every metric.Conclusion·The VJK-GIN model exhibits high stability and accuracy in identifying contrast-enhanced CT images of normal,benign,and malignant gallbladder conditions.

Objective To investigate the value of amide proton transfer(APT)imaging in evaluating lymph-vascular space inva-sion(LVSI)of cervical cancer.Methods A retrospective analysis was conducted on the data of cervical cancer patients with patho-logically confirmed LVSI status.Based on the presence of LVSI,the patients were divided into LVSI positive group and LVSI nega-tive group.All patients underwent diffusion weighted imaging(DWI)and APT imaging before treatment,and the apparent diffusion coefficient(ADC)and APT values of the lesions were measured.An independent sample t-test was used to compare the differences in ADC and APT values between the two groups.The sensitivity,specificity and area under the curve(AUC)of ADC,APT and ADC+APT in predicting LVSI were observed by receiver operating characteristic(ROC)curve,and the diagnostic performance of the three was compared by DeLong test.Results A total of 78 patients were included,of which 54 were LVSI negative and 24 were LVSI positive.The ADC values in the LVSI positive group were significantly lower than those in the LVSI negative group(P＜0.001),while the APT values in the LVSI positive group were significantly higher than those in the LVSI negative group(P＜0.001).The sensitivities of ADC,APT and ADC+APT in predicting LVSI were 79.17％,83.33％ and 87.50％,respectively,the specificities were 75.93％,55.56％ and 77.78％,respectively,and the AUC were 0.828,0.759 and 0.868,respectively,indicating that the diag-nostic performance of ADC+APT was better than that of ADC and APT alone(P＜0.001).Conclusion APT imaging can preop-eratively predict the presence of LVSI status in cervical cancer.When combined with ADC,its diagnostic accuracy is higher than that of APT alone,providing a new approach for evaluating LVSI in cervical cancer.