Analyzing molecular typing and clinical application of immunogenic cell death-related genes in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is considered one of the most common cancers, characterized by low early detection and high mortality rates, and is a global health challenge. Immunogenic cell death (ICD) is defined as a specific type of regulated cell death (RCD) capable of reshaping the tumor immune microenvironment by releasing danger signals that trigger immune responses, which would contribute to immunotherapy. METHODS: The ICD gene sets were collected from the literature. We collected expression data and clinical information from public databases for the HCC samples in our study. Data processing and mapping were performed using R software to analyze the differences in biological characteristics between different subgroups. The expression of the ICD representative gene in clinical specimens was assessed by immunohistochemistry, and the role of the representative gene in HCC was evaluated by various in vitro assays, including qRT-PCR, colony formation, and CCK8 assay. Lasso-Cox regression was used to screen prognosis-related genes, and an ICD-related risk model (ICDRM) was constructed. To improve the clinical value of ICDRM, Nomograms and calibration curves were created to predict survival probabilities. Finally, the critical gene of ICDRM was further investigated through pan-cancer analysis and single-cell analysis. RESULTS: We identified two ICD clusters that differed significantly in terms of survival, biological function, and immune infiltration. As well as assessing the immune microenvironment of tumors in HCC patients, we demonstrate that ICDRM can differentiate ICD clusters and predict the prognosis and effectiveness of therapy. High-risk subpopulations are characterized by high TMB, suppressed immunity, and poor survival and response to immunotherapy, whereas the opposite is true for low-risk subpopulations. CONCLUSIONS: This study reveals the potential impact of ICDRM on the tumor microenvironment (TME), immune infiltration, and prognosis of HCC patients, but also a potential tool for predicting prognosis.

A study of temperature variability on admissions and deaths for cardiovascular diseases in Northwestern China.

OBJECTIVE: To explore the effect of temperature variability (TV) on admissions and deaths for cardiovascular diseases (CVDs). METHOD: The admissions data of CVDs were collected in 4 general hospitals in Jinchang City, Gansu Province from 2013 to 2016. The monitoring data of death for CVDs from 2013 to 2017 were collected through the Jinchang City Center for Disease Control and Prevention. Distributed lag nonlinear model (DLNM) was combined to analyze the effects of TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) on the admissions and deaths for CVDs after adjusting confounding effects. Stratified analysis was conducted by age and gender. Then the attribution risk of TV was evaluated. RESULTS: There was a broadly linear correlation between TV and the admissions and deaths for CVDs, but only the association between TV and outpatient and emergency room (O&ER) visits for CVDs have statistically significant. DTV and HTV have similar lag effect. Every 1 ℃ increase in DTV and HTV was associated with a 3.61% (95% CI: 1.19% ~ 6.08%), 3.03% (95% CI: 0.27% ~ 5.86%) increase in O&ER visits for CVDs, respectively. There were 22.75% and 14.15% O&ER visits for CVDs can attribute to DTV and HTV exposure during 2013-2016. Males and the elderly may be more sensitive to the changes of TV. Greater effect of TV was observed in non-heating season than in heating season. CONCLUSION: TV was an independent risk factor for the increase of O&ER visits for CVDs, suggesting effective guidance such as strengthening the timely prevention for vulnerable groups before or after exposure, which has important implications for risk management of CVDs.

Microbial diversity composition of apple tree roots and resistance of apple Valsa canker with different grafting rootstock types.

BACKGROUND: The composition and diversity of root microbial community are affected by plant genotypes and soil environment, which in turn affect plant growth and development. Grafting rootstock types of the apple tree can affect phenotypes in cultivation practice, but it is not clear whether grafting rootstock types can affect the composition and diversity of root microbial community and the resistance of apple tree to apple Valsa canker. METHODS: To explore root microbial differences and the correlation, 16S rRNA and ITS genes were sequenced using Novaseq technology. RESULTS: The results showed that the influence of grafting rootstock types on the composition of the root fungal community was greater than that of bacteria. And the bacterial community richness was higher in the healthy (OTUs: 1693) and dwarfing rootstock (OTUs: 1526) than in the disease (OTUs: 1181) and standard rootstock (OTUs: 1412), while the fungal community richness was the opposite. Moreover, the bacterial abundance of root zone, rhizosphere, and root endophytic microorganisms with the same grafting rootstock type exhibited a decreasing trend. Results of Nested PCR assay on soil and root tissue of Valsa mali showed that the content of V. mali in dwarfing rootstocks are lower than standard rootstocks. These results suggest that apple trees grafting with dwarfing rootstocks are more resistant to V. mali than standard rootstocks. CONCLUSIONS: Under different grafting types, the effect on the composition of fungal community in apple tree root was greater than that of bacteria. The bacterial community in dwarfing rootstocks is more abundant and diverse, including more beneficial microorganisms. Therefore, dwarfing rootstock is more conducive to the resistance to apple Valsa canker from biological control.

Cohort Profile Update: the China Metal-Exposed workers Cohort Study (Jinchang Cohort).

The Jinchang Cohort was an ongoing 20-year ambispective cohort with unique metal exposures to an occupational population. From January 2014 to December 2019, the Jinchang Cohort has completed three phases of follow-up. The baseline cohort was completed from June 2011 to December 2013, and a total of 48 001 people were included. Three phases of follow-ups included 46 713, 41 888, and 40 530 participants, respectively. The death data were collected from 2001 to 2020. The epidemiological, physical examination, physiological, and biochemical data of the cohort were collected at baseline and during follow-up. Biological specimens were collected on the baseline to establish a biological specimen bank. The concentrations of metals in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The new areas of research aim to study the all-cases mortality, the burden of diseases, heavy metals and diseases, and the course of the chain from disease to high-risk outcomes using a combination of macro and micro means, which provided a scientific basis to explore the pathogenesis of multi-etiology and multi-disease and to evaluate the effects of the intervention measures in the population.

Analysis of droplet size uniformity and selection of spray parameters based on the biological optimum particle size theory.

Based on the theory of biological optimal particle size, the most easily attached droplets for different organisms have different particle sizes. To achieve the best average particle size, the droplet size in the atomization field must be more uniform and attain a high the adhesion rate. Therefore, during the application process, not only the average particle size of the droplets but also the influence of the uniformity of the droplets in the spray field must be considered. In this study, 20 small-angle fan nozzles ranging from 20° to 40° are used as the research objects. The droplet size information in the atomization field is obtained using a laser particle size analyzer, and the droplet uniformity under different parameters is calculated. The results showed that within the range of the parameters selected in the experiment, the droplet size increased with an increase in the flow rate, and decreased with an increase in the pressure. In addition, the angle had little effect on the droplet size. Increasing the spray height, spray angle, and pressure, while reducing the equivalent outlet diameter of the nozzle was beneficial to improve the uniformity of droplets. The order of the degree of influence of the four parameters on the uniformity of the droplets was height > equivalent outlet diameter (r) > pressure > spray angle, and the influence weights were 51.1%, 37.1%, 7.8%, 4.1%; 48.4%, 37.6%, 10%, and 4%. Under the condition of the parameter settings used in this experiment, the optimal atomization effect for the four intervals of 150-200 µm, 200-250 µm, 250-300 µm, and 300-400 µm was analyzed from the perspective of uniformity. The nozzle models with the best atomization effects in each interval were SS4003-0.3 MPa, SS4006-0.3 MPa, SS4008-0.3 MPa, and 633.512.30.CC-0.1 MPa.

Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway.

Breast cancer is one of the major malignant tumors in females, and currently, recurrence and metastasis are the main obstacles preventing effective breast cancer treatment. Biflavonoids of secondary metabolites from plants are excellent anticancer agents to fight sensitive and resistant breast cancer cell lines. In this study, six C-3'-C-6″ biflavonoids, including one new robustaflavone A (1, RF-A) and five known robustaflavone derivatives (2-6), were isolated from Selaginella trichoclada for the first time. We aimed to evaluate the inhibitory effects of compounds 1-6 against human breast cancer MCF-7 cells. Among the six compounds, RF-A showed the strongest activity, decreasing cell viability with an IC50 value of 11.89 µΜ. Furthermore, RF-A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways.

The effect and prediction of diurnal temperature range in high altitude area on outpatient and emergency room admissions for cardiovascular diseases.

PURPOSE: Diurnal temperature range (DTR) is a meteorological indicator closely associated with global climate change. Thus, we aim to explore the effects of DTR on the outpatient and emergency room (O&ER) admissions for cardiovascular diseases (CVDs), and related predictive research. METHODS: The O&ER admissions data for CVDs from three general hospitals in Jinchang of Gansu Province were collected from 2013 to 2016. A generalized additive model (GAM) with Poisson regression was employed to analyze the effect of DTR on the O&ER admissions for all cardiovascular diseases, hypertension, ischemic heart disease (IHD) and stoke. GAM was also used to preform predictive research of the effect of DTR on the O&ER admissions for CVDs. RESULTS: There were similar positive linear relationships between DTR and the O&ER visits with the four cardiovascular diseases. And the cumulative lag effects were higher than the single lag effects. A 1 °C increase in DTR corresponded to a 1.30% (0.99-1.62%) increase in O&ER admissions for all cardiovascular diseases. Males and elderly were more sensitivity to DTR. The estimates in non-heating season were higher than in heating season. The trial prediction accuracy rate of CVDs based on DTR was between 59.32 and 74.40%. CONCLUSIONS: DTR has significantly positive association with O&ER admissions for CVDs, which can be used as a prediction index of the admissions of O&ER with CVDs.

Triterpenoids with antiproliferative activities from the twigs and leaves of Melaleuca linariifolia.

One new pentacyclic triterpenoid, urs-12,16-dien-3-one (1), together with twelve known pentacyclic triterpenoids (2‒13), were isolated from the twigs and leaves of Melaleuca linariifolia. Their structures were characterized by their 1D- and 2 D-NMR spectra analysis and mass spectra studies. Furthermore, all isolated compounds were tested the inhibitory effect on proliferation of six human cancer cell lines in vitro, including NCI-H441, NCI-H460, A549, SKOV3, hela, and caki-1 cells. Among them, compounds 3, 5, 7, 9, 12, and 13 exhibited moderate antiproliferative activities with IC50 values ranging from 3.85 to 33.31 µM.

Two New Abietane Diterpenoids from Selaginella moellendorffii Hieron.

Two new abietane diterpenoids, (3S,5R,10S)-3-hydroxy-12-O-demethyl-11-deoxy-19(4→3)-abeo-cryptojaponol, 12,19-dihydroxyabieta-8,11,13-trien-7-one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D- and 2D-NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non-small-cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC50 values ranging from 16.28 to 40.67 µM.

Extracting Diameter at Breast Height with a Handheld Mobile LiDAR System in an Outdoor Environment.

Mobile laser scanning (MLS) is widely used in the mapping of forest environments. It has become important for extracting the parameters of forest trees using the generated environmental map. In this study, a three-dimensional point cloud map of a forest area was generated by using the Velodyne VLP-16 LiDAR system, so as to extract the diameter at breast height (DBH) of individual trees. The Velodyne VLP-16 LiDAR system and inertial measurement units (IMU) were used to construct a mobile measurement platform for generating 3D point cloud maps for forest areas. The 3D point cloud map in the forest area was processed offline, and the ground point cloud was removed by the random sample consensus (RANSAC) algorithm. The trees in the experimental area were segmented by the European clustering algorithm, and the DBH component of the tree point cloud was extracted and projected onto a 2D plane, fitting the DBH of the trees using the RANSAC algorithm in the plane. A three-dimensional point cloud map of 71 trees was generated in the experimental area, and estimated the DBH. The mean and variance of the absolute error were 0.43 cm and 0.50, respectively. The relative error of the whole was 2.27%, the corresponding variance was 15.09, and the root mean square error (RMSE) was 0.70 cm. The experimental results were good and met the requirements of forestry mapping, and the application value and significance were presented.

Effect of pocket irrigation with antimicrobial on prevention of pacemaker pocket infection: a meta-analysis.

BACKGROUND: The presence of cardiac implantable electronic devices (CIEDs) pocket infection is difficult to treat, causing serious clinical outcomes, but little is known for prevention. Results from some studies suggested that pocket irrigation could reduce infection while others showed conflicting results. We pooled the effects of pocket irrigations on the prevention of pocket infection by meta-analysis methods. METHOD: Relevant studies published before June, 2017 were retrieved mainly by the computer-based search of PubMed, Cochrane, EMBASE, Web of Science, Chinese BioMedical, Global Health and BIOSIS Previews databases. Estimations of relative ratios (RRs) and 95% confidence intervals (95% CIs) were pooled. Subgroup analyses according to potential key factors affecting the effects were conducted, which was confirmed by meta-regression. Sensitivity analysis and test for publication bias were also performed. RESULTS: We identified 10 studies providing data of 5467 patients receiving CIEDs implantations. Pooled infection rates were 1.48 and 3.49% respectively for medication and saline irrigation groups. Meta-analysis showed that medication irrigation conferred protection to pocket infection (RR = 0.44, 95% CI: 0.31-0.63). Subgroup analysis showed that antibiotics, rather than non-antibiotics (antiseptics) exerting the protection. The first and second lines antibiotics against staphylococcus aureus, which is the main pathogen for pocket infection, were both effective (RR = 0.42, 95% CI: 0.24-0.75 and RR = 0.34, 95% CI: 0.20-0.58 respectively for first line and second line therapies). Meta-regression revealed that region and class of irrigation medication completely explained the variance among studies and implied that effects of region were masked by medication types. Sensitivity analysis did not showed any significant change of the result and publication bias were not statistical significance. CONCLUSION: Pocket irrigation with antibiotics were effective for reducing pocket infection and should be encouraged in CIEDs implantation.

Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB pathway.

Recent studies show that Polydatin (PD) extracted from the roots of Polygonum cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti-inflammatory activity in several experimental models. In this study, we investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced mastitis in mice and elucidated the potential mechanisms. In mice with S aureus-induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory cells, ameliorated the mammary structural damage, and inhibited the activity of myeloperoxidase, a biomarker of neutrophils accumulation. Furthermore, PD treatment dose-dependently decreased the levels of TNF-α, IL-1ß, IL-6 and IL-8 in the mammary gland tissues. PD treatment also dose-dependently decreased the expression of TLR2, MyD88, IRAK1, IRAK4 and TRAF6 as well as the phosphorylation of TAK1, MKK3/6, p38 MAPK, IκB-α and NF-κB in the mammary gland tissues. In mouse mammary epithelial cells (mMECs) infected by S aureus in vitro, pretreatment with PD dose-dependently suppressed the upregulated pro-inflammatory cytokines and signaling proteins, and the nuclear translocation of NF-κB p65 and AP-1. A TLR2-neutralizing antibody mimicked PD in its suppression on S aureus-induced upregulation of MyD88, p-p38 and p-p65 levels in mMECs. PD (50, 100 µg/mL) affected neither the growth of S aureus in vitro, nor the viability of mMECs. In conclusion, PD does not exhibit antibacterial activity against S aureus, its therapeutic effects in mouse S aureus-induced mastitis depend on its ability to down-regulate pro-inflammatory cytokine levels via inhibiting TLR2-mediated activation of the p38 MAPK/NF-κB signaling pathway.

[Study on extraction process of coumarin in a Mongolian drug Chagan-sorlo (Radix Glehniae)].

The present paper discusses ultrasonic extraction method aided extraction of coumarin from a Mongolian drug, Chagan-sorlo (Radix Glehniae), aiming to study out how much coumarin contained in Chagan-sorlo, and to provide the scientific basis and production guidance for extracting coumarin from Chagan-sorlo. Under different conditions the coumarin in Chagan-sorlo was extracted by ultrasonic, measured and analyzed, and then HPLC was used to carry out the measurement. Result showed that with solvent volume fraction of 70%, extraction time of 20 min, ultrasonic power of 175 W, temperature of 25 degrees C, solid-liquid ratio of 1 : 20, and 80-100 mesh extraction, the coumarin extraction reaches the highest yield.

Escherichia coli-Induced cGLIS3-Mediated Stress Granules Activate the NF-κB Pathway to Promote Intrahepatic Cholangiocarcinoma Progression.

Patients with concurrent intrahepatic cholangiocarcinoma (ICC) and hepatolithiasis generally have poor prognoses. Hepatolithiasis is once considered the primary cause of ICC, although recent insights indicate that bacteria in the occurrence of hepatolithiasis can promote the progression of ICC. By constructing in vitro and in vivo ICC models and patient-derived organoids (PDOs), it is shown that Escherichia coli induces the production of a novel RNA, circGLIS3 (cGLIS3), which promotes tumor growth. cGLIS3 binds to hnRNPA1 and G3BP1, resulting in the assembly of stress granules (SGs) and suppression of hnRNPA1 and G3BP1 ubiquitination. Consequently, the IKKα mRNA is blocked in SGs, decreasing the production of IKKα and activating the NF-κB pathway, which finally results in chemoresistance and produces metastatic phenotypes of ICC. This study shows that a combination of Icaritin (ICA) and gemcitabine plus cisplatin (GP) chemotherapy can be a promising treatment strategy for ICC.

Necroptosis enhances 'don't eat me' signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Prevalence of chronic kidney disease in a city of Northwestern China: a cross-sectional study.

AIM: Chronic kidney disease (CKD) is increasingly recognized as a global health issue. There is a paucity of published data on the prevalence and risk factors of CKD in less-developed regions. This study aims to evaluate and update the prevalence and risk factors of CKD in a city of Northwestern China. METHODS: Based on a prospective cohort study, a cross-sectional baseline survey was conducted between 2011 and 2013. The data on the epidemiology interview, physical examination, and clinical laboratory test were all collected. In this study, 41,222 participants were selected from 48,001 workers in the baseline after excluding objects with incomplete information. The crude and standardized prevalence of CKD were calculated. An unconditional logistic regression model was used to analyze the risk factors associated with CKD among male and female. RESULTS: One thousand seven hundred eighty-eight people were diagnosed with CKD, including 1180 males and 608 females. The crude prevalence of CKD was 4.34% (4.78% males and 3.68% females). The standardized prevalence was 4.06% (4.51% males and 3.60% females). The prevalence of CKD increased with age and was higher in males than in females. In multivariable logistic regression, CKD was significantly associated with the increasing age, drinking, never or occasionally exercise, overweight or obesity, being unmarried, diabetes, hyperuricemia, dyslipidemia and hypertension. CONCLUSION: In this study, the prevalence of CKD was lower than that of the national cross-sectional study. Lifestyle, hypertension, diabetes, hyperuricemia and dyslipidemia were the main risk factors of CKD. The prevalence and risk factors differ between male and female.

A novel protein elicitor (PeSy1) from Saccharothrix yanglingensis induces plant resistance and interacts with a receptor-like cytoplasmic kinase in Nicotiana benthamiana.

Previously, we reported a rare actinomycete Saccharothrix yanglingensis Hhs.015 with strong biocontrol ability, which can colonize plant tissues and induce resistance, but the key elicitor and immune mechanisms were unclear. In this study, a novel protein elicitor screened from the genome of Hhs.015, PeSy1 (protein elicitor of S. yanglingensis 1), could induce a strong hypersensitive response (HR) and resistance in plants. The PeSy1 gene encodes an 11 kDa protein with 109 amino acids that is conserved in Saccharothrix species. PeSy1-His recombinant protein induced early defence events such as a cellular reactive oxygen species burst, callose deposition, and the activation of defence hormone signalling pathways, which enhanced Nicotiana benthamiana resistance to Sclerotinia sclerotiorum and Phytophthora capsici, and Solanum lycopersicum resistance to Pseudomonas syringae pv. tomato DC3000. Through pull-down and mass spectrometry, candidate proteins that interacted with PeSy1 were obtained from N. benthamiana. We confirmed the interaction between receptor-like cytoplasmic kinase RSy1 (Response to PeSy1) and PeSy1 using co-immunoprecipitation, bimolecular fluorescence complementation, and microscale thermophoresis. PeSy1 treatment promoted up-regulation of marker genes in pattern-triggered immunity. The cell death it elicited was dependent on the co-receptors NbBAK1 and NbSOBIR1, suggesting that PeSy1 acts as a microbe-associated molecular pattern from Hhs.015. Additionally, RSy1 positively regulated PeSy1-induced plants resistant to S. sclerotiorum. In conclusion, our results demonstrated a novel receptor-like cytoplasmic kinase in the plant perception of microbe-associated molecular patterns, and the potential of PeSy1 in induced resistance provided a new strategy for biological control of actinomycetes in agricultural diseases.

Three new metabolites from the endophyte Fusarium proliferatum T2-10.

One new cyclopeptide, cyclo-(L-Trp-L-Phe-L-Phe) (1), one new 2-pyridone derivative, fusarone A (3), and one new natural indole derivative, ethyl 3-indoleacetate (4), along with six known compounds were isolated from the endophytic fungus Fusarium proliferatum T2-10. The planar structures of three new compounds were identified by spectral methods including 1D and 2D NMR techniques, and the absolute configuration of compound 1 was elucidated by Marfey-MS method. In addition, all compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Compound 2 showed remarkable cytotoxic activities against two human hepatoma cell lines SMMC7721 and HepG2 with IC50 values of 5.89 ± 0.74 and 6.16 ± 0.52 µM, and showed moderate antibacterial activities against Staphylococcus aureus and Enterococcus faecalis with MIC values of 7.81 and 15.62 µg/mL, respectively.

A Novel Trojan Horse Nanotherapy Strategy Targeting the cPKM-STMN1/TGFB1 Axis for Effective Treatment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is characterized by its dense fibrotic microenvironment and highly malignant nature, which are associated with chemotherapy resistance and very poor prognosis. Although circRNAs have emerged as important regulators in cancer biology, their role in ICC remains largely unclear. Herein, a circular RNA, cPKM is identified, which is upregulated in ICC and associated with poor prognosis. Silencing cPKM in ICC cells reduces TGFB1 release and stromal fibrosis, inhibits STMN1 expression, and suppresses ICC growth and metastasis, moreover, it also leads to overcoming paclitaxel resistance. This is regulated by the interactions of cPKM with miR-199a-5p or IGF2BP2 and by the ability of cPKM to stabilize STMN1/TGFB1 mRNA. Based on these findings, a Trojan horse nanotherapy strategy with co-loading of siRNA against cPKM (si-cPKM) and paclitaxel (PTX) is developed. The siRNA/PTX co-loaded nanosystem (Trojan horse) efficiently penetrates tumor tissues, releases si-cPKM and paclitaxel (soldiers), promotes paclitaxel sensitization, and suppresses ICC proliferation and metastasis in vivo. Furthermore, it alleviates the fibrosis of ICC tumor stroma and reopens collapsed tumor vessels (opening the gates), thus enhancing the efficacy of the standard chemotherapy regimen (main force). This novel nanotherapy provides a promising new strategy for ICC treatment.

Construction of a theoretical model for fan nozzles with precise atomization angles for plant protection.

The fan nozzle is widely used in the process of pest control in agriculture and forestry. The spray angle of the nozzle is an important characterization parameter in the atomization of liquids. The spray angle of the nozzle is an important characterizing parameter in the liquid atomization process. It affects the flow field at the exit of the nozzle, thereby affecting the size and velocity of the droplets, and further affecting the deposition effect of the droplets on the crop. Therefore, its research is of great significance for improving the deposition of liquid on plants and controlling pests and related diseases. Based on the classical theory of predecessors and considering the parameters of the flat fan nozzle, we further optimized the theory at the structural level by means of a simulation test and built a spray angle theoretical model taking into account the parameters of the inner chamber of the nozzle. We arrived at the following conclusions: (1) the average error of the spray angle measured by the simulation test and the actual test spray angle was 2.95%, the maximum spray angle deviation value was 2.81°, and the result proves that the simulation test parameter setting is accurate; and (2) the average error between the actual measured value and the theoretical model calculation value was 3.56%, the maximum spray angle deviation was 4°, through the actual test comparison, and the spray angle error of the theoretical model was within the allowable error range of industry production. It was proved that the model could effectively reflect the changing law of spray angle of the flat fan nozzle.