A cuproptosis-related gene expression signature predicting clinical prognosis and immune responses in intrahepatic cholangiocarcinoma detected by single-cell RNA sequence analysis.

BACKGROUND: Cholangiocarcinoma represents a malignant neoplasm originating from the hepatobiliary tree, with a subset of tumors developing inside the liver. Intrahepatic cholangiocarcinomas (ICC) commonly exhibit an asymptomatic presentation, rendering both diagnosis and treatment challenging. Cuproptosis, an emerging regulated cell death pathway induced by copper ions, has garnered attention recently. As cancer cells show altered copper metabolism and comparatively higher copper needs, cuproptosis may play a role in the development of ICC. However, studies investigating this possibility are currently lacking. METHODS: Single-cell and bulk RNA sequence data were analyzed, and correlations were established between the expression of cuproptosis-related molecules and ICC patient survival. Genes with predicting survival were used to create a CUPT score using Cox and LASSO regression and tumor mutation burden (TMB) analysis. The CIBERSORT software was employed to characterize immune cell infiltration within the tumors. Furthermore, immune infiltration prediction, biological function enrichment, and drug sensitivity analyses were conducted to explore the potential implications of the cuproptosis-related signature. The effects of silencing solute carrier family 39 member 4 gene (SLC39A4) expression using siRNA were investigated using assays measuring cell proliferation, colony formation, and cell migration. Key genes of cuproptosis were detected by western blotting. RESULTS: The developed CUPT score divided patients into high and low CUPT score groups. Those with a low score had significantly better prognosis and longer survival. In contrast, high CUPT scores were associated with worse clinical outcomes and significantly higher TMB. Comparisons of the two groups also indicated differences in the immune infiltrate present in the tumors. Finally, we were able to identify 95 drugs potentially affecting the cuproptosis pathway. Some of these might be effective in the treatment of ICC. The in vitro experiments revealed that suppressing the expression of SLC39A4 in ICC cell lines resulted in reduced cell proliferation, colony formation, and cell migration. It also led to an increase in cell death and the upregulation of key genes associated with cuproptosis, namely ferredoxin 1 (FDX1) and dihydrolipoyl transacetylase (DLAT). These findings strongly suggest that this cuproptosis-associated molecule may play a pivotal role in the development and metastasis of ICC. CONCLUSIONS: Changes in the expression of a cuproptosis-related gene signature can predict the clinical prognosis of ICC with considerable accuracy. This supports the notion that cuproptosis influences the diversity and complexity of the immune microenvironment, mutational landscape, and biological behavior of ICC. Understanding this pathway better may hold promise for the development of innovative strategies in the management of this disease.

Effects of paternal ionizing radiation exposure on fertility and offspring's health.

Purpose: The intergenerational effects of ionizing radiation remain controversial. Extensive insights have been revealed for DNA mutations and cancer incidence in progeny, yet many of these results were obtained by immediate post-radiation mating. However, conception at short times after radiation exposure is likely to be avoided. After a long period of fertility recovery, whether unexposed sperm derived from exposed spermatogonia would challenge the health of the offspring is not yet clearly demonstrated. Methods: Ten-week-old C57BL/6J males underwent whole-body acute γ irradiation at 0 and 6.4 Gy. Testes and sperm were collected at different times after radiation to examine reproductive changes. The reproductive, metabolic, and neurodevelopmental parameters were measured in the offspring of controls and the offspring derived from irradiated undifferentiated spermatogonia. Results: Paternal fertility was lost after acute 6.4 Gy γ radiation and recovered at 10-11 weeks post irradiation in mice. The reproductive, metabolic, and neurodevelopmental health of offspring born to irradiated undifferentiated spermatogonia were comparable to those of controls. Conclusion: The male mice could have healthy offspring after recovery from the damage caused by ionizing radiation.

[Indoor simulation training system for brain-controlled wheelchair based on steady-state visual evoked potentials].

Brain-controlled wheelchair (BCW) is one of the important applications of brain-computer interface (BCI) technology. The present research shows that simulation control training is of great significance for the application of BCW. In order to improve the BCW control ability of users and promote the application of BCW under the condition of safety, this paper builds an indoor simulation training system based on the steady-state visual evoked potentials for BCW. The system includes visual stimulus paradigm design and implementation, electroencephalogram acquisition and processing, indoor simulation environment modeling, path planning, and simulation wheelchair control, etc. To test the performance of the system, a training experiment involving three kinds of indoor path-control tasks is designed and 10 subjects were recruited for the 5-day training experiment. By comparing the results before and after the training experiment, it was found that the average number of commands in Task 1, Task 2, and Task 3 decreased by 29.5%, 21.4%, and 25.4%, respectively ( P < 0.001). And the average number of commands used by the subjects to complete all tasks decreased by 25.4% ( P < 0.001). The experimental results show that the training of subjects through the indoor simulation training system built in this paper can improve their proficiency and efficiency of BCW control to a certain extent, which verifies the practicability of the system and provides an effective assistant method to promote the indoor application of BCW.

[Mechanisms and applications of transcutaneous electrical nerve stimulation in analgesia].

Transcutaneous electrical nerve stimulation (TENS), as a non-pharmacological and non-invasive analgesic therapy with low-cost, has been widely used to relieve pain in various clinical applications, by delivering current pulses to the skin area to activate the peripheral nerve fibers. Nevertheless, analgesia induced by TENS varied in the clinical practice, which could be caused by the fact that TENS with different stimulus parameters has different biological mechanisms in relieving pain. Therefore, to advance our understanding of TENS in various basic and clinical studies, we discussed (1) neurophysiological and biochemical mechanisms of TENS-induced analgesia; (2) relevant factors that may influence analgesic effects of TENS from the perspectives of stimulus parameters, including stimulated position, pulse parameters (current intensity, frequency, and pulse width), stimulus duration and used times in each day; and (3) applications of TENS in relieving clinical pain, including post-operative pain, chronic low back pain and labor pain. Finally, we propose that TENS may involve multiple and complex psychological neurophysiological mechanisms, and suggest that different analgesic effects of TENS with different stimulus parameters should be taken into consideration in clinical applications. In addition, to optimize analgesic effect, we recommend that individual-based TENS stimulation parameters should be designed by considering individual differences among patients, e.g., adaptively adjusting the stimulation parameters based on the dynamic ratings of patients' pain.

[Simulation research of respiratory monitoring with magnetic detection electrical impedance tomography].

In order to explore the feasibility of applying magnetic detection electrical impedance tomography(MDEIT) on respiratory monitoring, aiming at the forward problem of magnetic detection electrical impedance tomography, we calculated the electric potential and current density distribution inside the imaging object by using the finite element method. We then got magnetic induction intensity outside the object at the end of exhaling and inhaling according to Biot-Savart's law. The results showed that the magnetic induction intensity at the end of inhaling was 8.875%,less than that at the end of exhaling. By the simulation results, we could understand the difference of magnetic induction intensity value surrounding the lung at the end of exhaling and inhaling due to the change of lung volume and electrical conductivity distribution better. Our research laid the foundation for the late image reconstruction and clinical disease detection.

A new theoretical model for transmembrane potential and ion currents induced in a spherical cell under low frequency electromagnetic field.

Time-varying electromagnetic fields (EMF) can induce some physiological effects in neuronal tissues, which have been explored in many applications such as transcranial magnetic stimulation. Although transmembrane potentials and induced currents have already been the subjects of many theoretical studies, most previous works about this topic are mainly completed by utilizing Maxwell's equations, often by solving a Laplace equation. In previous studies, cells were often considered to be three-compartment models with different electroconductivities in different regions (three compartments are often intracellular regions, membrane, and extracellular regions). However, models like that did not take dynamic ion channels into consideration. Therefore, one cannot obtain concrete ionic current changes such as potassium current change or sodium current change by these models. The aim of the present work is to present a new and more detailed model for calculating transmembrane potentials and ionic currents induced by time-varying EMF. Equations used in the present paper originate from Nernst-Plank equations, which are ionic current-related equations. The main work is to calculate ionic current changes induced by EMF exposure, and then transmembrane potential changes are calculated with Hodgkin-Huxley model. Bioelectromagnetics. 37:481-492, 2016. © 2016 Wiley Periodicals, Inc.

[Study on Sleep Staging Methods Based on Heart Rate Variability Analysis].

In order to realize sleep staging automatically and conveniently,we used support vector machine(SVM)to analyze the correlation between heart rate variability and sleep stage experimentally.R-R intervals(RRIs)from 33 cases of sleep clinical data of Tianjin Thoracic Hospital were extracted and analyzed by principal component analysis(PCA).The SVM method was used to establish the model and predict the five sleep stages.The prediction accuracy of three-sleep-stage was higher than 80%,in contrast to sleep scoring annotations marked by physiological experts based on electroencephalogram(EEG)golden standard.The result showed that there was a good correlation between heart rate variability and sleep staging.This method is an important supplement to the traditional sleep staging method and has a great value for clinical application.

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis.

BACKGROUND: The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC. METHODS: Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing. RESULTS: Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3-18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up. CONCLUSIONS: Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT01790061.

A NIR-remote controlled upconverting nanoparticle: an improved tool for living cell dye-labeling.

In living cells, due to the selective permeability and complicated cellular environment, the uptake efficiency and fluorescence decay of organic dyes during dye-labeling may be influenced, which may eventually result in poor fluorescent imaging. In this work, a protocol of UCNs@mSiO2-(FA and Azo) core-shell nanocarriers was designed and prepared successfully. The core-shell nanocarriers were assembled from two parts, including a mesoporous silica shell surface modified by folate (FA) and azobenzene (Azo), and an upconverting nanocrystal (UCN) core. The mesoporous silica shell is used for loading organic dyes and conjugating folate which helps to enhance the cellular uptake of nanocarriers. The UCN core works as a transducer to convert near infrared (NIR) light to local UV and visible light to activate a back-and-forth wagging motion of azobenzene molecules on the surface, while the azobenzene acts as a molecular impeller for propelling the release of organic dyes. The nanocarriers of loading organic dyes can maintain the stability of the fluorescent imaging effect better than free organic dyes. The experimental results show that with the help of the nanoparticle, cell uptake efficiency of the model dyes of rhodamine and 4', 6-diamidino-2-phenylindole (DAPI) was significantly improved. The release of dyes can only be triggered by NIR light exposure and their quantity is highly dependent on the duration of NIR light exposure, thus realizing NIR-regulated dye release spatiotemporally. Our work may open a novel avenue for precisely controlling UCN-based living cell imaging in biotechnology and diagnostics, as well as studying cell dynamics, cell-cell interactions, and tissue morphogenesis.

Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing.

OBJECTIVE: Sufficient fetal DNA in a maternal plasma sample is required for accurate aneuploidy detection via noninvasive prenatal testing, thus highlighting a need to understand the factors affecting fetal fraction. METHOD: The MaterniT21™ PLUS test uses massively parallel sequencing to analyze cell-free fetal DNA in maternal plasma and detect chromosomal abnormalities. We assess the impact of a variety of factors, both maternal and fetal, on the fetal fraction across a large number of samples processed by Sequenom Laboratories. RESULTS: The rate of increase in fetal fraction with increasing gestational age varies across the duration of the testing period and is also influenced by fetal aneuploidy status. Maternal weight trends inversely with fetal fraction, and we find no added benefit from analyzing body mass index or blood volume instead of weight. Strong correlations exist between fetal fractions from aliquots taken from the same patient at the same blood draw and also at different blood draws. CONCLUSION: While a number of factors trend with fetal fraction across the cohort as a whole, they are not the sole determinants of fetal fraction. In this study, the variability for any one patient does not appear large enough to justify postponing testing to a later gestational age.

Identification of MYB Transcription Factor, a Regulator Related to Hydrolysable Tannin Synthesis in Canarium album L., and Functional Analysis of CaMYBR04.

Hydrolysed tannins (HTs) are polyphenols, which are related to the astringency, flavour, colour, stability, medicinal value and other characteristics of many fruits and vegetables. The biosynthetic mechanism of the majority of HTs remains unknown, and many biosynthetic pathways of HTs are speculative conclusions that have not been confirmed. The fruit of Canarium album L. (Chinese olive), which is notable for its pharmacological and edible properties, is rich in HTs. The fruit has a distinctive bitter and astringent taste when initially consumed, which mellows to a sweet sensation upon chewing. HTs serve as the primary material basis for the formation of the Chinese olive fruit's astringent quality and pharmacological effects. In this study, the fruit of C. album Changying was utilised as the research material. The objective of this study was to provide a theoretical basis for the quality control of Chinese olive fruit and the application and development of its medicinal value. In addition, the study aimed to identify and screen related MYB transcription factors involved in the synthesis of HTs in the fruit and to clarify the mechanism of MYBs in the process of synthesis and regulation of HTs in Chinese olive fruit. The principal findings were as follows. A total of 83 differentially expressed Chinese olive MYB transcription factors (CaMYBs) were identified, including 54 1R-MYBs (MYB-related), 25 2R-MYBs (R2R3-MYBs), 3 3R-MYBs, and 1 4R-MYB. Through trend analysis and correlation analysis, it was found that CaMYBR04 (Isoform0032534) exhibited a significantly higher expression (FPKM) than the other CaMYBs. The full-length cDNA sequence of CaMYBR04 was cloned and transformed into strawberry. The results demonstrated that CaMYBR04 significantly enhanced the fruit's hydrolysable tannin content. Consequently, this study elucidated the function of CaMYBR04, a regulator of the Chinese olive fruit hydrolysable tannin synthesis pathway, and established a theoretical foundation for the synthesis and regulation of fruit HTs.

The effect of transcranial electrical stimulation on the relief of mental fatigue.

Objective: The presence of mental fatigue seriously affects daily life and working conditions. Non-invasive transcranial electrical stimulation has become an increasingly popular tool for relieving mental fatigue. We investigated whether transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) could be used to alleviate the state of mental fatigue in a population of healthy young adults and compared their effects. Methods: We recruited 10 participants for a blank control, repeated measures study. Each participant received 15 min of anodal tDCS, α-tACS, and blank stimulation. Participants were required to fill in the scale, perform the test task and collect ECG signals in the baseline, fatigue and post-stimulus states. We then assessed participants' subjective fatigue scale scores, test task accuracy and HRV characteristics of ECG signals separately. Results: We found that both anodal tDCS and α-tACS significantly (P < 0.05) reduced subjective fatigue and improved accuracy on the test task compared to the blank group, and the extent of change was greater with tACS. For the HRV features extracted from ECG signals. After tACS intervention, SDNN (t = -3.241, P = 0.002), LF (t = -3.511, P = 0.001), LFn (t = -3.122, P = 0.002), LFn/HFn (-2.928, P = 0.005), TP (t = -2.706, P = 0.008), VLF (t = -3.002, P = 0.004), SD2 (t = -3.594, P = 0.001) and VLI (t = -3.564, P = 0.001) showed a significant increasing trend, and HFn (t = 3.122, P = 0.002), SD1/SD2 (t = 3.158, P = 0.002) and CCM_1 (t = 3.106, P = 0.003) showed a significant decreasing trend. After tDCS intervention, only one feature, TINN, showed a significant upward trend (P < 0.05). The other features showed non-significant changes but roughly the same trend as the tACS group. Conclusion: Both tDCS and α-tACS can be effective in relieving mental fatigue, and α-tACS is more effective than tDCS. This study provides theoretical support for tDCS with α-tACS having a alleviating effect on mental fatigue and the use of ECG as a valid objective assessment tool.

Ambulatory ECG noise reduction algorithm for conditional diffusion model based on multi-kernel convolutional transformer.

Ambulatory electrocardiogram (ECG) testing plays a crucial role in the early detection, diagnosis, treatment evaluation, and prevention of cardiovascular diseases. Clear ECG signals are essential for the subsequent analysis of these conditions. However, ECG signals obtained during exercise are susceptible to various noise interferences, including electrode motion artifact, baseline wander, and muscle artifact. These interferences can blur the characteristic ECG waveforms, potentially leading to misjudgment by physicians. To suppress noise in ECG signals more effectively, this paper proposes a novel deep learning-based noise reduction method. This method enhances the diffusion model network by introducing conditional noise, designing a multi-kernel convolutional transformer network structure based on noise prediction, and integrating the diffusion model inverse process to achieve noise reduction. Experiments were conducted on the QT database and MIT-BIH Noise Stress Test Database and compared with the algorithms in other papers to verify the effectiveness of the present method. The results indicate that the proposed method achieves optimal noise reduction performance across both statistical and distance-based evaluation metrics as well as waveform visualization, surpassing eight other state-of-the-art methods. The network proposed in this paper demonstrates stable performance in addressing electrode motion artifact, baseline wander, muscle artifact, and the mixed complex noise of these three types, and it is anticipated to be applied in future noise reduction analysis of clinical dynamic ECG signals.

Optical Analysis Method for Turbid Media Based on Wedge-Shaped Cells at Different Angles.

The wedge-shaped sample cell, by offering a comprehensive representation of scattering information in turbid media, significantly enhances the informational content conveyed by spectral images compared to flat sample cells. To further refine the accuracy of turbid medium component detection utilizing wedge-shaped sample cells, this work undertakes modeling and analysis of the influence of different wedge angles on detection precision. In this study, employing a 5° gradient in the incident angle of light, we investigate the impact of incident angles ranging from 10 to 45° on the turbid medium component analysis. Validation experiments are performed by utilizing solutions of Indian ink and fat emulsion at varying ratios. Experimental findings demonstrate that under identical experimental conditions, the wedge-shaped sample cell model at an incident angle of 35° yields optimal analysis results. Utilizing partial least-squares regression (PLSR) for the corresponding optical parameters, the highest value of Rp reached 0.980, with an RMSEP of 0.002. When compared to the model with a 30° incident angle, Rp increased by 0.033, and RMSEP decreased by 0.008. In comparison to the flat sample cell model, Rp increased by 0.041, and RMSEP decreased by 0.004. This study, through continuous variation of wedge angles and PLSR modeling and prediction, further enhances the accuracy of turbid medium component detection, laying an experimental foundation for subsequent analysis of turbid medium components based on wedge-shaped sample cells.

Advances in Non-Invasive Neuromodulation Techniques for Improving Cognitive Function: A Review.

Non-invasive neuromodulation techniques are widely utilized to study and improve cognitive function, with the aim of modulating different cognitive processes. For workers performing high-intensity mental and physical tasks, extreme fatigue may not only affect their working efficiency but may also lead to cognitive decline or cognitive impairment, which, in turn, poses a serious threat to their physical health. The use of non-invasive neuromodulation techniques has important research value for improving and enhancing cognitive function. In this paper, we review the research status, existing problems, and future prospects of transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial magnetic stimulation (TMS), and transcutaneous acupoint stimulation (TAS), which are the most studied physical methods in non-invasive neuromodulation techniques to improve and enhance cognition. The findings presented in this paper will be of great reference value for the in-depth study of non-invasive neuromodulation techniques in the field of cognition.

Simulation study of abdominal hemorrhage based on magnetic induction tomography.

Abdominal hemorrhage is an important clinical disease that can be life-threatening in severe cases. Therefore, timely detection and treatment of abdominal hemorrhage is crucial for the health and safety of patients. Magnetic induction tomography is a non-invasive, nonradioactive, and non-contact electromagnetic imaging technology with potential application value for disease screening and continuous monitoring. In this paper, a simulation model of electrical impedance distribution close to the real human abdominal tissue was constructed, and based on this model, the magnetic induction tomography simulation method of internal bleeding was studied by the finite element numerical method, and the comparison was verified by phantom experiments. The eddy current density distribution inside the abdominal tissue and the magnetic induction phase data at the tissue boundary are solved, and sensitivity analysis of phase differences caused by changes in the radius and position of bleeding volume was conducted, and three sensitivity indicators were proposed. Both the simulation and phantom experiment show that when there are six types of tissues with different conductivity in the abdomen, the radius of bleeding increases from 10 to 30 mm, and the radius phase difference sensitivity index Ar increases approximately linearly monotonically. Its radius transformation sensitivity Kr is 3.0961 × 10-5°/cm. When the position of the bleeding volume changes, the sensitivity index Ax of the x-axis displacement phase difference shows a quasilinear monotonic decrease, and the x-axis displacement sensitivity Kx is -6.3744 × 10-6°/cm. The y-axis displacement phase difference sensitivity Ay index shows a quasilinear relationship and monotonically increases, with a y-axis displacement sensitivity Ky of 5.2870 × 10-4°/cm. The results indicate that the phase difference sensitivity before and after the occurrence of bleeding can be used as a quantitative monitoring indicator to monitor the occurrence and trend of intra-abdominal hemorrhage, laying the foundation for the preliminary screening and continuous monitoring of abdominal hemorrhage diseases using magnetic induction imaging.

Cascaded utilization of magnetite nanoparticles@onion-like carbons from wastewater purification to supercapacitive energy storage.

Developing high-performance carbon-based materials for environmental and energy-related applications produces solid waste with secondary pollution to the environment at the end of their service lives. It is still challenging to utilize these functional materials in a sustainable manner in different fields. In this study, we demonstrate a cascaded utilization of an Fe3O4@onion-like carbon (Fe3O4@OLC) structure from wastewater adsorbents to a supercapacitor electrode. The structure was formed by carbonizing Fe3O4@oleic acid monodisperse nanoparticles into interconnected Fe3O4@OLCs and subsequent insufficient acid etching. The hollow OLCs in the outside region of the hybrid structure provide high surface area and the encapsulated Fe3O4 nanoparticles in the inside region offer high ferromagnetism. The three-dimensionally interconnected graphitic layers are advantageous for efficient separation and high conductivity. As a result, the maximum saturation adsorption capacity of insufficiently etched interconnected Fe3O4@OLCs can reach up to 90.2 mg g-1 and they can be efficiently separated under a magnetic field. Furthermore, the hybrid structure is thermally transformed into N-doped HOLCs, which are demonstrated to be a high-performance supercapacitor electrode with high specific capacitance and high electrochemical stability. The cascaded utilization of the hybrid structure in this study is meaningful for eco-friendly development of functional materials for environmental and energy storage applications.

Sigma-1 receptor regulates the endoplasmic reticulum stress pathway in the protective mechanism of dexmedetomidine against hyperoxia-induced lung injury.

Perioperative hyperoxia therapy is of great significance to save the lives of patients, but little is known about the possible mechanisms that induce hyperoxia-induced acute lung injury (HALI) and the measures for clinical prevention and treatment. In this experiment, the models were established with a feeding chamber with automatic regulation of oxygen concentration. The results showed that with the increase in inhaled oxygen concentration and the prolongation of exposure time, the severity of lung injury also increases significantly, reaching the diagnostic indication of HALI after 48 h of inhaling 95 % oxygen concentration. Subsequently, according to the dynamic changes of apoptosis in lung specimens, and the expression changes in Sig-1R-regulated ER stress pathway proteins (Sig-1R, GRP78, p-PERK, ATF6, IRE1, Caspase-12, ATF4, CHOP, Caspase-3 and p-JNK), it was confirmed that the Sig-1R-regulated ER stress signaling pathway was involved in the occurrence of HALI. To explore the preventive and therapeutic effects of routine clinical medication on HALI during the perioperative period, our research group selected dexmedetomidine (Dex) with lung protection. The experimental results revealed that Dex partially reversed the changes in the expression levels of Sig-1R-regulated ER stress pathway proteins. These results preliminarily confirmed that Dex may inhibit apoptosis induced by high oxygen concentration through the Sig-1R-regulated ER stress signaling pathway, thus playing a protective role in HALI.

Construction and drug screening of Co-culture system using extrahepatic cholangiocarcinoma organoids and tumor-associated macrophages.

Patient-derived organoids (PDOs) have been proposed as a novel in vitro tumor model that can be applied to tumor research and drug screening. However, current tumor organoid models lack components of the tumor microenvironment, particularly tumor-associated macrophages(TAMs).We collected peripheral blood and tumor samples from 6 patients with extrahepatic cholangiocarcinoma(eCCA). Monocytes were induced into TAMs by cytokine and conditioned medium, and then co-cultured with tumor organoids. Our comprehensive analysis and comparison of histopathology and genomics results confirmed that this co-culture model can better capture intra- and inter-tumor heterogeneity retain the specific mutations of the original tumor. Drug sensitivity data in vitro revealed that gemcitabine and cisplatin are effective drugs for cholangiocarcinoma, but TAMs in the tumor microenvironment promote organoids growth and chemotherapy resistance. In conclusion, our organoid model of cholangiocarcinoma co-cultured with TAMs can not only shorten the model construction cycle, but also preserve the heterogeneity of original tumors to improve the accuracy of drug screening, and can also be applied to the researches of TAMs and tumors.