Salicylic Acid Spray Delays Sand Pear Fruit Senescence during Room Temperature Shelf Life by Regulating Antioxidant Capacity and Senescence-Related Genes.

'Whangkeumbae' (Pyrus pyrifolia) is a variety of sand pear fruit well-known for its smooth surface and good taste. However, the fruit quality is adversely affected by postharvest ethylene production. Therefore, improving postharvest shelf life by regulating fruit senescence is critical to promoting the 'Whangkeumbae' fruit industry. Here, we investigated the effect of salicylic acid (SA) spray on fruit senescence in sand pears during room temperature shelf life. Exogenous SA reduced polyphenol oxidase (PPO) activity and malondialdehyde (MDA) content during room temperature shelf life. Additionally, SA effectively maintained the fruit skin coloration and increased the activity of antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX). SA treatment inhibited PpPPO1 expression and upregulated PpSOD1, PpAPX6, and PpGST2 expression. Furthermore, SA application downregulated the expression of PpACO2, PpEIN3a, PpNCED1, and PpAOC2, while upregulating PpNPR-1, PpTAR2, and PpCOMT1 during room temperature shelf life. SA treatment also influenced cell wall metabolism and modification genes by inhibiting PpPG1, PpPME2, and PpCEL3 and inducing PpPGIP1 expression. Additionally, SA treatment affected sugar and acid metabolism genes and increased the expression of PpSPS1, PpSUS1, PpSOT1, PpTMT4, PpSWEET15, and PpcyNAD-MDH, but suppressed the expression of PpcyNADP-ME. The Pearson correlation analysis indicated that PPO activity and MDA content were positively correlated with the expression of PpPPO1, PpACO2, PpEIN3a, PpNCED1, PpAOC2, PpPG1, PpPME2, PpCEL3, and PpcyNDA-MDH. Conversely, these factors were negatively associated with the activities of SOD, POD, CAT, and APX, as well as the expression levels of PpSOD1, PpPOD1, PpCAT1, PpAPX6, PpGST2, PpNPR-1, PpTAR2, PpCOMT1, PpPGIP1, PpSPS1, PpSUS1, PpSOT1, PpTMT4, PpSWEET15, and PpcyNAD-MDH. Our results reveal that exogenous SA could delay fruit senescence in sand pear fruit by regulating various biochemical and molecular mechanisms and can be used to effectively extend fruit shelf life during room temperature storage. However, further research is necessary to determine whether the fruits sprayed with SA are suitable for direct human consumption.

Informing immunotherapy with multi-omics driven machine learning.

Progress in sequencing technologies and clinical experiments has revolutionized immunotherapy on solid and hematologic malignancies. However, the benefits of immunotherapy are limited to specific patient subsets, posing challenges for broader application. To improve its effectiveness, identifying biomarkers that can predict patient response is crucial. Machine learning (ML) play a pivotal role in harnessing multi-omic cancer datasets and unlocking new insights into immunotherapy. This review provides an overview of cutting-edge ML models applied in omics data for immunotherapy analysis, including immunotherapy response prediction and immunotherapy-relevant tumor microenvironment identification. We elucidate how ML leverages diverse data types to identify significant biomarkers, enhance our understanding of immunotherapy mechanisms, and optimize decision-making process. Additionally, we discuss current limitations and challenges of ML in this rapidly evolving field. Finally, we outline future directions aimed at overcoming these barriers and improving the efficiency of ML in immunotherapy research.

Associations of environmental cadmium exposure with kidney damage: Exploring mediating DNA methylation sites in Chinese adults.

Environmental exposure is widely recognized as the primary sources of Cadmium (Cd) in the human body, and exposure to Cd is associated with kidney damage in adults. Nevertheless, the role of DNA methylation in Cd-induced kidney damage remains unclear. This study aimed to investigate the epigenome-wide association of environmental Cd-related DNA methylation changes with kidney damage. We included 300 non-smoking adults from the China in 2019. DNA methylation profiles were measured with Illumina Infinium MethylationEPIC BeadChip array. Linear mixed-effect model was employed to estimate the effects of urinary Cd with DNA methylation. Differentially methylated positions (DMPs) associated with urinary Cd were then tested for the association with kidney damage indicators. The mediation analysis was further applied to explore the potential DNA methylation based mediators. The prediction model was developed using a logistic regression model, and used 1000 bootstrap resampling for the internal validation. We identified 27 Cd-related DMPs mapped to 20 genes after the adjustment of false-discovery-rate for multiple testing among non-smoking adults. 17 DMPs were found to be associated with both urinary Cd and kidney damage, and 14 of these DMPs were newly identified within the Chinese. Mediation analysis revealed that DNA methylation of cg26907612 and cg16848624 mediated the Cd-related reduced kidney damage. In addition, ten variables were selected using the LASSO regression analysis and were utilized to develop the prediction model. It found that the nomogram model predicted the risk of kidney damage caused by environmental Cd with a corrected C-index of 0.779. Our findings revealed novel DMPs associated with both environmental Cd exposure and kidney damage among non-smoking adults, and developed an easy-to-use nomogram-illustrated model using these novel DMPs. These findings could provide a theoretical basis for formulating prevention and control strategies for kidney damage from the perspective of environmental pollution and epigenetic regulation.

Progressive coronal caudal curve after corrective osteotomies for congenital cervicothoracic scoliosis: incidence and predictors.

OBJECTIVE: Postoperative progressive coronal caudal curve (PCC) was characterized by a postoperative de novo caudal S-curve ≥ 20° following congenital cervicothoracic scoliosis (CTS) corrective osteotomies, and at least 20° greater than the preoperative measurement, while the incidence was uncertain and the pathogenesis was equivocal. The objective of this study was to investigate the morbidity and potential factors contributing to PCC following CTS surgery. METHODS: This study reviewed 72 CTS patients between 2005 and 2021. Patients were categorized into two groups according to the absence or presence of PCC at last follow-up, namely the nonprogressive curve group (NPC-group) and the progressive curve group (PC-group). Demographics, radiographic data and the Scoliosis Research Society-22 (SRS-22) questionnaire results were reviewed. Multivariate linear regression analyses were utilized to determine possible predictors for PCC. RESULTS: PCC was observed in 11 (15%) of the total 72 patients. Compared with the NPC-group, the PC-group exhibited greater postoperative residual local curve (24.0 ± 9.7° vs. 9.1 ± 4.4°, P < 0.001), upper instrumented vertebra (UIV) tilt (16.9 ± 7.4° vs. 6.2 ± 3.7°, P < 0.001), T1 tilt (14.3 ± 9.4° vs. 6.6 ± 3.9°, P = 0.022) and neck tilt (10.1 ± 6.7° vs. 3.7 ± 2.5, P = 0.009). The multivariable linear regression demonstrated that the larger postoperative UIV tilt, residual local curve and neck tilt were associated with PCC. In addition, patients with PCC showed lower SRS-22 scores in terms of pain, mental health, self-image and satisfaction (P < 0.05). CONCLUSIONS: The morbidity of PCC was 15% in CTS patients who underwent corrective osteotomies. Greater residual local curve, postoperative UIV tilt and neck tilt were identified as predictors for PCC.

Biomechanical characteristics of Sanders type II and III calcaneal fractures fixed by open reduction and internal fixation and percutaneous minimally invasive fixation.

BACKGROUND: This work investigated the differences in the biomechanical properties of open reduction and internal fixation (ORIF) and percutaneous minimally invasive fixation (PMIF) for the fixation of calcaneal fractures (Sanders type II and III calcaneal fractures as examples) through finite element analysis. METHODS: Based on CT images of the human foot and ankle, according to the principle of three-point fixation, namely the sustentaculum tali, the anterior process and the calcaneal tuberosity were fixed. Three-dimensional finite element models of Sanders type II and III calcaneal fractures fixed by ORIF and PMIF were established. The proximal surfaces of the tibia, fibula and soft tissue were constrained, and ground reaction force and Achilles tendon force loads were added to simulate balanced standing. RESULTS: The maximum stress was 80.54, 211.59 and 113.88 MPa for the calcaneus, screws and plates in the ORIF group and 70.02 and 209.46 MPa for the calcaneus and screws in the PMIF group, respectively; the maximum displacement was 0.26, 0.21 and 0.12 mm for the calcaneus, screws and plates in the ORIF group and 0.20 and 0.14 mm for the calcaneus and screws in the PMIF group, respectively. The values obtained from the simulation were within the permissible stress and elastic deformation range of the materials used in the model, and there was no significant stress concentration. The maximum stress and displacement of the calcaneus and implants were slightly lower in the PMIF group than in the ORIF group when fixing Sanders type II and III calcaneal fractures. CONCLUSIONS: This study may provide a reference for optimising the design of implants, the development of individualised preoperative plans and the choice of clinical surgical approach.

Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature.

BACKGROUND: TMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level. METHODS: Based on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA). RESULTS: A signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion. CONCLUSIONS: Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.

The effectiveness of online breastfeeding education and support program on mothers of preterm infants: A quasi-experimental study.

OBJECTIVE: To develop a WeChat-mini-program-based Online breastfeeding education and support program and explore its impacts on promoting mothers of preterm infants' breastfeeding knowledge, attitudes, self-efficacy, and rates. DESIGN, SETTING, AND PARTICIPANTS: This was a quasi-experimentation with two-group comparisons. The eligible preterm mother-infant pairs were recruited from the NICU within seven days postpartum. The first 25 mothers admitted to the NICU during the study period were included in the control group, and the following 25 mothers were in the intervention group according to the admission order of their preterm infants. A generalized linear mixed model was used to detect the effects of the online intervention program and the interaction effects of group and time. INTERVENTIONS: The participants received a 3-month online breastfeeding intervention from a WeChat mini program for the intervention group. MEASUREMENTS: Mothers of preterm infants' breastfeeding knowledge, attitudes, self-efficacy, and breastfeeding rates of different patterns were respectively evaluated by the Breastfeeding Knowledge Questionnaire (BKQ), Iowa Infant Feeding Attitude Scale (IIFAS), and Breastfeeding Self-Efficacy Scale (BSES) at three different points of times including before intervention (T0), at one month postpartum (T1) and three months postpartum (T2). FINDINGS: The breastfeeding knowledge significantly differed between the two groups but without differences between different time points and in the grouping*time interaction. Within the intervention group, significant improvements were observed from T0 to T2 and T1 to T2. No significant differences in breastfeeding attitudes, self-efficacy, and breastfeeding rates were found between and within groups. KEY CONCLUSIONS: The WeChat-mini-program-based online breastfeeding intervention may improve the breastfeeding knowledge level of mothers of preterm infants but has no significant impact on mothers' breastfeeding attitudes, breastfeeding self-efficacy, and breastfeeding rates. IMPLICATIONS FOR PRACTICE: The WeChat mini program can be used to improve the breastfeeding knowledge level of mothers of preterm infants. Future interventions need to target both mothers of preterm infants and their family members by combing online and offline approaches.

A Comprehensive Pan-cancer Analysis of the Biological Immunomodulatory Function and Clinical Value of CD27.

Background: CD27 is an immunological checkpoint gene, plays a critical function inInhibition or activation of cancer immunity. The CD27/CD27L axis is its pathway of action. Therefore, our goal was to examine the predictive role of CD27 in the clinical prognosis of 33 cancer types and its functions in cancer progression, as well as explore the link between pan-cancer CD27 gene expression and immune infiltration. Methods: By comprehensive use of datasets and methods from TCGA, cBioPortal, GTEx, HPA, KM-plotter, Spearman, CellMinerTM, R packages and RT-qPCR, we delved deeper into the potential impact of the CD27 on cancer development. These include expression differences, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways, TMB, MSI, and prognosis. Also, we explored CD27 interactions with different drugs. Results: The results showed that, mutated CD27 was highly expressed in most cancers. The CD27 showed strong diagnostic value in 4 cancers and marked a positive prognosis for CESC, intracervical adenocarcinoma, HNSC, and endometrial cancer, and a poor prognosis for UVM. In addition, CD27 affects multiple immune and inflammatory signaling pathways and is positively correlated with immune cell infiltration, T cell differentiation, macrophage M1 polarization, stromal infiltration, and drug sensitivity. DNA methylation is involved in CD27 expression in cancer. Conclusion: CD27, which is mutated in cancers and appears widely highly expressed and altered tumor immune invasion and stromal invasion by affecting multiple immune-related and inflammation signaling pathways, plays a significant role in CESC, HNSC, UCEC and UVM, and may be used as a therapeutic target for related cancers.

Randomized comparison of the four-hook anchor device and hook-wire use for the preoperative localization of pulmonary nodules.

OBJECTIVE: To compare the efficacy and safety of preoperative localization of small pulmonary nodules (SPNs) with 4-hook anchor device and hook-wire before video-assisted thoracoscopic surgery. METHODS: Patients with SPNs scheduled for computed tomography-guided nodule localization before video-assisted thoracoscopic surgery between May 2021 and June 2021 at our center were randomized to either 4-hook anchor group or hook-wire group. The primary end point was intraoperative localization success. RESULTS: After randomization, 28 patients with 34 SPNs were assigned to the 4-hook anchor group and 28 patients with 34 SPNs to the hook-wire group. The operative localization success rate was significantly greater in the 4-hook anchor group than in the hook-wire group (94.1% [32/34] vs 64.7% [22/34]; P = .007). All lesions in the 2 groups were successfully resected under thoracoscopy, but 4 patients in the hook-wire group who required transition from wedge resection to segmentectomy or lobectomy because of unsuccessful localization. Total localization-related complication rate was significantly lower in the 4-hook anchor group than in the hook-wire group (10.3% [3/28] vs 50.0% [14/28]; P = .004). The rate of chest pain requiring analgesia after the localization procedure was significantly lower in the 4-hook anchor group than in the hook-wire group (0 vs 5/28, 17.9%; P = .026). There were no significant differences in localization technical success rate, operative blood loss, hospital stay length and hospital cost between the 2 groups (all P > .05). CONCLUSIONS: The use of the 4-hook anchor device for SPN localization offers advantages over the traditional hook-wire technique.

Establishment of a Model for Human Hypertrophic Scar Using Tissue Engineering Method.

BACKGROUND: Treatment of human hypertrophic scar (HS) is a challenge for plastic surgeons, whereas the clinical and experimental research has been limited due to the lack of an ideal model of human HS tissue. OBJECTIVE: To establish a model of human HS using tissue engineering method, to improve the research for HS in the clinic and laboratory. METHODS: Hypertrophic scar fibroblasts (HSFBs) were transferred to polylactic acid (PLA)/polyglycolic acid (PGA) scaffolds. Biocompatibility of HSFBs-PLA/PGA composites was evaluated using scanning electron microscopy. Composites of HSFBs-PLA/PGA were implanted in subcutaneous pockets in athymic mice after 4 weeks in vitro culture. A re-entry operation was performed to obtain the HS-like tissues after 12 weeks of in vivo culture. The histological stain, the expression of type I collagen, the proliferation ability, and vitality of HSFBs were compared between human HS tissue and HS-like tissue. RESULTS: The structure of PLA/PGA scaffolds facilitates HSFBs adhesion and proliferation. The HSFBs-PLA/PGA composites were in vivo cultured for 12 weeks, and then HS-like tissues were harvested from nude athymic mice. There was no statistical significance in the expression of type I collagen, cell cycle, and cell proliferation between human HS tissue and HS-like tissue. CONCLUSION: The authors successfully established a model of human HS using the tissue engineering method, which could provide HS-like tissue for research. And it also could provide enough HS-like tissues to help reduce experimental variability within groups. This model can be used to investigate in prevention and treatment of HS and further explore the mechanisms of HS.

Nickel Single Atom Density-Dependent CO2 Efficient Electroreduction.

The transition metal-nitrogen-carbon (M─N─C) with MNx sites has shown great potential in CO2 electroreduction (CO2RR) for producing high value-added C1 products. However, a comprehensive and profound understanding of the intrinsic relationship between the density of metal single atoms and the CO2RR performance is still lacking. Herein, a series of Ni single-atom catalysts is deliberately designed and prepared, anchored on layered N-doped graphene-like carbon (x Ni1@NG-900, where x represents the Ni loading, 900 refers to the temperature). By modulating the precursor, the density of Ni single atoms (DNi) can be finely tuned from 0.01 to 1.19 atoms nm-2. The CO2RR results demonstrate that the CO faradaic efficiency (FECO) predominantly increases from 13.4% to 96.2% as the DNi increased from 0 to 0.068 atoms nm-2. Then the FECO showed a slow increase from 96.2% to 98.2% at -0.82 V versus reversible hydrogen electrode (RHE) when DNi increased from 0.068 to 1.19 atoms nm-2. The theoretical calculations are in good agreement with experimental results, indicating a trade-off relationship between DNi and CO2RR performance. These findings reveal the crucial role of the density of Ni single atoms in determining the CO2RR performance of M─N─C catalysts.

Multi-omics integration analysis unveils heterogeneity in breast cancer at the individual level.

Identifying robust breast cancer subtypes will help to reveal the cancer heterogeneity. However, previous breast cancer subtypes were based on population-level quantitative gene expression, which is affected by batch effects and cannot be applied to individuals. We detected differential gene expression, genomic, and epigenomic alterations to identify driver differential expression at the individual level. The individual driver differential expression reflected the breast cancer patients' heterogeneity and revealed four subtypes. Mesenchymal subtype as the most aggressive subtype harbored deletion and downregulated expression of genes in chromosome 11q23 region. Specifically, silencing of the SDHD gene in 11q23 promoted the invasion and migration of breast cancer cells in vitro by the epithelial-mesenchymal transition. The immunologically hot subtype displayed an immune-hot microenvironment, including high T-cell infiltration and upregulated PD-1 and CTLA4. Luminal and genomic-unstable subtypes showed opposite macrophage polarization, which may be regulated by the ligand-receptor pairs of CD99. The integration of multi-omics data at the individual level provides a powerful framework for elucidating the heterogeneity of breast cancer.

The expression and clinical value of LRP11, FUBP1 and TET1 in cervical cancer.

Cervical cancer is the second leading cause of cancer death among women worldwide. Identification of effective genes along with biological markers as targeting agents is very necessary for the diagnosis and treatment of this disease. Bioinformatics techniques along with genetic and molecular investigations have provided the possibility of studying different levels of information such as the genome, transcriptome, proteome, and metabolize with high depth and accuracy. The collection of these data provides comprehensive and valuable information about the investigated phenotypes, including complex diseases such as cancer. In this study, we examined three genes LRP11, FUBP1, and TET1 related to cervical cancer. The results of this study showed that the level of expression of these genes is high in lymph nodes and the thyroid and is less in the pancreas and liver. Also, the expression level of the FUBP1 gene is higher than that of LRP11, and the expression level of the LRP11 gene is higher than that of TET1. Regarding the structure and proteomics of the studied genes, it can be seen that due to the presence of more domains in the LRP11 and FUBP1 genes, these genes probably independently participate in various functions and have a wider range of activity than the TET1 gene. Also, the analysis of the stability of the examined genes showed that the stability of the FUBP1 gene is relatively higher than that of the TET1 gene, and this gene is also more stable than the LRP11 gene. Considering that these genes are effective key genes for the early detection of cervical cancer, it is hoped that they will be used as markers in the diagnosis and treatment of cervical cancer.

KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract.

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

Infigratinib, a Selective Fibroblast Growth Factor Receptor Inhibitor, Suppresses Stent-Induced Tissue Hyperplasia in a Rat Esophageal Model.

PURPOSE: Stent-induced tissue hyperplasia remains a challenge for the application of self-expanding metal stents in the management of esophageal stricture. This study aimed to evaluate the efficacy of infigratinib, which is a selective fibroblast growth factor receptor inhibitor, in the prevention of stent-induced tissue hyperplasia in a rat esophageal model. METHODS: Twenty-four male Sprague-Dawley rats underwent esophageal stent placement and were randomized to receive 1 ml of vehicle, 5 mg/kg infigratinib in 1 ml of vehicle, or 10 mg/kg infigratinib in 1 ml of vehicle via naso-gastric tube once daily for 28 days. Follow-up fluoroscopy was performed on postoperative day 28, and the stented esophageal tissues were harvested for histological and immunofluorescence examinations. RESULTS: All rats survived until euthanasia on postoperative day 28 without procedure-related adverse events. The incidence of stent migration was 12.5%, 12.5% and 25% in the control group, the 5 mg/kg infigratinib group and, the 10 mg/kg infigratinib group, respectively. The percentage of granulation tissue area, the submucosal fibrosis thickness, the number of epithelial layers, the degree of inflammatory cell infiltration, the degree of collagen deposition, the number of fibroblast growth factor receptor 1 (FGFR1)-expressing myofibroblasts, and the number of proliferating myofibroblasts were all significantly lower in both infigratinib groups than in the control group (P < 0.05) but were not significantly different between the two infigratinib groups (P > 0.05). CONCLUSIONS: Infigratinib significantly suppresses stent-induced tissue hyperplasia by inhibiting FGFR1-mediated myofibroblast proliferation and profibrotic activities in a rat esophageal model.

Network pharmacology analysis of Icariside II against bladder cancer.

As a global health threat, bladder cancer (BC) is a common urological disease characterized by a high risk of progression and recurrence. Icariside II (ICA-II), a flavonol glycoside, exhibits antitumor ability in various tumors. However, there is no systematic study exploring the pharmacological mechanism of ICA-II in BC. We used public databases to obtain potential targets of ICA-II and related genes in BC. Bioinformatics analysis and molecular docking were used to identify potential targets and signaling pathways. Then, MTT, cell cycle assays and western blot (WB) were used to validate the predicted pathways in bladder cell lines, and in situ bladder cancer models were also established to verify the effect of ICA-II. Our research demonstrated that these ICA-II hub genes were related to the cell cycle. Then, our molecular docking analysis confirmed the interaction between ICA-II and CCNB1. In addition, our in vitro experiment demonstrated that ICA-II restrained the proliferation of BC cells mainly by blocking the cell cycle. WB also verified that ICA-II decreased the expression levels of CCNB1. In situ BC models showed that ICA-II had no hepatotoxicity or nephrotoxicity and could suppress the growth of in situ BC. In summary, during this study, we found that ICA-II had low toxicity in the kidney and liver. Network pharmacology was used, and both cell and animal experiments verified that ICA-II has a good therapeutic effect on bladder cancer, which may inhibit the proliferation and progression of bladder cancer by blocking the cell cycle of BC cells.

Spatial Transcriptomic Cell-type Deconvolution Using Graph Neural Networks.

Spatially resolved transcriptomics performs high-throughput measurement of transcriptomes while preserving spatial information about the cellular organizations. However, many spatially resolved transcriptomic technologies can only distinguish spots consisting of a mixture of cells instead of working at single-cell resolution. Here, we present STdGCN, a graph neural network model designed for cell type deconvolution of spatial transcriptomic (ST) data that can leverage abundant single-cell RNA sequencing (scRNA-seq) data as reference. STdGCN is the first model incorporating the expression profiles from single cell data as well as the spatial localization information from the ST data for cell type deconvolution. Extensive benchmarking experiments on multiple ST datasets showed that STdGCN outperformed 14 published state-of-the-art models. Applied to a human breast cancer Visium dataset, STdGCN discerned spatial distributions between stroma, lymphocytes and cancer cells for tumor microenvironment dissection. In a human heart ST dataset, STdGCN detected the changes of potential endothelial-cardiomyocyte communications during tissue development.

CircHIPK3 negatively regulates autophagy by blocking VCP binding to the Beclin 1 complex in bladder cancer.

Circular RNA HIPK3 (circHIPK3) mediates the progression of multiple cancers, including bladder cancer, by regulating cell migration, autophagy and epithelial mesenchymal transition. However, the mechanism by which circHIPK3 regulates autophagy in bladder cancer cells remains unclear. Autophagy is a common self-protection mechanism in eukaryotic cells and is essential for cell survival and death regulation. However, it is unclear whether circHIPK3 affects the level of autophagy in bladder cancer through binding proteins, and the potential regulatory mechanism is unknown. Here, we found that circHIPK3 levels were significantly lower and autophagy-related proteins were significantly upregulated in bladder cancer cells and tissues compared to normal controls. CircHIPK3 downregulation promoted bladder cancer cell proliferation, while circHIPK3 overexpression inhibited proliferation. CircHIPK3 overexpression significantly suppressed autophagy in bladder cancer cells. Overexpression of circHIPK3 did not affect VCP protein expression but inhibited the VCP/Beclin 1 interaction. VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy.

Modified Patent Hemostasis Strategy Based on the Platelet Counts for Transradial Access Chemoembolization in Patients with Hepatocellular Carcinoma: A Prospective Single-Center Study.

Objective: This study aimed to investigate the shortest compression time to achieve hemostasis and the optimal hemostasis strategy in patients treated with transradial access chemoembolization (TRA-TACE). Methods: From October 2019 to October 2021, 119 consecutive patients with hepatocellular carcinoma (HCC) who underwent 134 sessions of TRA-TACE were included in this prospective single-center study. The compression time was measured by decompressing the device for 30 min, and thereafter, every 10 min after the procedure until complete hemostasis was achieved. Results: Technical success was achieved for all TRA procedures. None of the patients experienced major TRA-related adverse events. Minor adverse events occurred in 7.5% of the patients. The mean compression time was 31.8 ± 5.0 min. Factors that may impact hemostasis were analyzed by univariate and multivariate analyses, and a platelet count < 100×109 /L (p = 0.016, odds ratio = 3.942) was found to be an independent factor that could predict the failure to achieve hemostasis within 30 min. For patients with a platelet count < 100×109 /L, the compression time required to achieve hemostasis was 60 min. For patients with a platelet count ≥ 100×109 /L, the compression time required to achieve hemostasis was 40 min. Conclusion: To achieve hemostasis in patients with HCC treated with TRA-TACE, compression for 60 min is sufficient for those with a platelet count < 100×109 /L, and compression for 40 min is sufficient for those with a platelet count ≥ 100×109 /L.

Self-assembly and self-delivery of the pure nanodrug dihydroartemisinin for tumor therapy and mechanism analysis.

Dihydroartemisinin (DHA), a plant-derived natural product, has recently been proven to be an effective therapeutic agent for cancer treatment. Nevertheless, the poor water solubility and low bioavailability of DHA seriously impede its clinical applications. Herein, a simple and green strategy based on the self-assembly of DHA was developed to synthesize carrier-free nanoparticles (NPs). The resulting nanodrug (DHA NPs) was formed by the self-assembly of DHA molecules via hydrogen bonding and hydrophobic interactions. The DHA NPs exhibited a near-spherical morphology with narrow size distribution, favorable drug encapsulation efficiency (>92%), excellent stability, and on-demand drug release behavior. Furthermore, the in vitro and in vivo experiments revealed that the DHA NPs exhibited significantly higher therapeutic efficacy than the DHA equivalent. In addition, we further explored the potential molecular mechanism of the DHA NPs by utilizing RNA-seq technology and western blotting analysis, which demonstrated that the p53 signaling pathway plays a crucial part in the process of inhibiting tumor cell growth and inducing apoptosis. This work not only reveals the rationale for developing pure nanodrugs via the self-assembly of natural small molecules for oncotherapy but also the investigation of the antitumor mechanism and provides novel theoretical support for the clinical usage of DHA.