Application of Organoids in Regenerative Medicine.

Regenerative medicine mainly relies on heterologous transplantation, often hindered by sample availability and ethical issues. Furthermore, patients are required to take immunosuppressive medications to prevent adverse side effects. Stem cell-derived 3D-organoid culture has provided new alternatives for transplantation and regenerative medicine. Scholars have combined organoids with tissue engineering technology to improve reproducibility, the accuracy of constitution and throughput, and genetic correction to achieve a more personalized therapy. Here, we review the available applications of organoids in regenerative medicine and the current challenges concerning this field.

MRI Fat-Saturated T2-Weighted Radiomics Model for Identifying the Ki-67 Index of Soft Tissue Sarcomas.

BACKGROUND: Ki-67 expression has been shown to be an important risk factor associated with prognosis in patients with soft tissue sarcomas (STSs). Its assessment requires fine-needle biopsy and its accuracy can be influenced by tumor heterogeneity. PURPOSE: To develop and test an MRI-based radiomics nomogram for identifying the Ki-67 status of STSs. STUDY TYPE: Retrospective. POPULATION: A total of 149 patients at two independent institutions (training cohort [high Ki-67/low ki-67]: 102 [52/50], external validation cohort [high Ki-67/low ki-67]: 47 [28/19]) with STSs. FIELD STRENGTH/SEQUENCE: Fat-saturated T2-weighted imaging (FS-T2WI) with a fat-suppressed fast spin/turbo spin echo sequence at 1.5 T or 3 T. ASSESSMENT: After radiomics feature extraction, logistic regression (LR), random forest (RF), support vector machine (SVM), and k-nearest neighbor (KNN) were used to construct radiomics models to distinguish between high and low Ki-67 status. Clinical-MRI characteristics included age, gender, location, size, margin, and MRI morphological features (size, margin, signal intensity, and peritumoral hyperintensity) were assessed. Univariate and multivariate logistic regression analysis were applied for screening significant risk factors. Radiomics nomogram was constructed by radiomics signature and risk factors. STATISTICAL TESTS: Model performances (discrimination, calibration, and clinical usefulness) were validated in the validation cohort. The nomogram was assessed using the Harrell index of concordance (C-index), calibration curve analysis. The clinical utility of the model was assessed by decision curve analysis (DCA). RESULTS: LR, RF, SVM, and KNN models represented AUCs of 0.789, 0.755, 0.726, and 0.701 in the validation cohort (P > 0.05). The nomogram had a C-index of 0.895 (95% CI: 0.837-0.953) in the training cohort and 0.852 (95% CI: 0.796-0.957) in the validation cohort and it demonstrated good calibration and clinical utility (P = 0.972 for the training cohort and P = 0.727 for the validation cohort). DATA CONCLUSION: This MRI-based radiomics nomogram developed showed good performance in identifying Ki-67 expression status in STSs. TECHNICAL EFFICACY STAGE: 2.

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health.

A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.

[Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats].

Objective: To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. Methods: A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). Results: CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Conclusion: Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

Diet Influences the Gut Microbial Diversity and Olfactory Preference of the German Cockroach Blattella germanica.

The gut microbiota of insects has been proven to play a role in the host's nutrition and foraging. The German cockroach, Blattella germanica, is an important vector of various pathogens and causes severe allergic reactions in humans. Food bait is an effective and frequently used method of controlling this omnivorous insect. Thus, understanding the relationships among diet, gut microbiota, and olfactory preferences could be useful for optimizing this management strategy. In this study, B. germanica was exposed to different foods, i.e., high-fat diet, high-protein diet, high-starch diet, and dog food (as control). Then their gut microbial and olfactory responses were investigated. 16S rRNA gene sequencing confirmed that the gut microbiota significantly differed across the four treatments, especially in relation to bacteria associated with the metabolism and digestion of essential components. Behavioral tests and the antenna electrophysiological responses showed that insects had a greater preference for other types of diets compared with their long-term domesticated diet. Moreover, continuously providing a single-type diet could change almost all the OR genes' expression of B. germanica, especially BgORco, which was significantly repressed compared to control. These results indicate that diet can shape the gut microbiota diversity and drive the olfactory preference of B. germanica. The association between gut microbiota profiles and diets can be utilized in managing B. germanica according to their olfactory preference.

Resistance to insecticides and synergistic and antagonistic effects of essential oils on dimefluthrin toxicity in a field population of Culex quinquefasciatus Say.

In this work, we firstly tested five spatial repellent pyrethroids, meperfluthrin, dimefluthrin, heptafluthrin, metofluthrin and transfluthrin, to determine the susceptibility of pyrethroids to field strains of Culex quinquefasciatus using adult topical bioassay. The results showed that though field strains exhibited the highest resistance to dimefluthrin among the selected five pyrethroids, it still can be considered low resistance in the scale of Cui et al. (2006; 2007). Then, the aim of this study was to optimise the synergistic efficacy of essential oils combined with dimefluthrin and explore the major contribution composition of eucalyptus oil, basil oil and cinnamon oil as natural synergist of dimefluthrin against the field populations of C. quinquefasciatus. GC-MS analysis showed 1,8-cineole, eugenol and trans-cinnamaldehyde were the main chemical components of eucalyptus oil, basil oil and cinnamon oil, respectively. The results of bioactivity showed that eucalyptus oil and 1,8-cineole have highly fumigant knock-down activity to the adults, showing KT50 (the median knockdown time) of 5.76 and 4.27 min at the concentration of 24.2 µL/L; basil oil and eugenol, cinnamon oil and trans-cinnamaldehyde have highly fumigant toxicity to the adults, showing LD50 of 1.00 and 0.79, 1.26 and 1.03 µL/L, respectively. Three effective main essential oil components were selected to prepare binary mixtures, which combined with dimefluthrin against the field population of Culex quinquefasciatus. 1,8-cineole+eugenol (9:1, w/w), 1,8-cineole+trans-cinnamaldehyde (1:1, w/w) and trans-cinnamaldehyde+eugenol (9:1, w/w) combined with dimefluthrin (10:1, w/w) were the most synergistic interaction, showed SR (synergistic ratio) values of 1.2471, 1.5709 and 1.1969; KT50 of 11.68, 9.51 and 10.67 min respectively, by quadrate box method. In addition, to validate the stable synergistic interaction of 1,8-cineole+trans-cinnamaldehyde (1:1, w/w) combined with dimefluthrin (10:1, w/w), the SR values were about 1.3, and KT50 values were 38.72-50.26 min by simulated house method. Overall, our results pointed out the promising potential of these essential oils to increase the efficacy of dimefluthrin. It might be expected that these essential oils could be developed to a useful botanical synergist of dimefluthrin for the control of the field populations of C. quinquefasciatus.

Parametric modeling of whole-genome sequencing data for CNV identification.

Copy number variants (CNVs) constitute an important class of genetic variants in human genome and are shown to be associated with complex diseases. Whole-genome sequencing provides an unbiased way of identifying all the CNVs that an individual carries. In this paper, we consider parametric modeling of the read depth (RD) data from whole-genome sequencing with the aim of identifying the CNVs, including both Poisson and negative-binomial modeling of such count data. We propose a unified approach of using a mean-matching variance stabilizing transformation to turn the relatively complicated problem of sparse segment identification for count data into a sparse segment identification problem for a sequence of Gaussian data. We apply the optimal sparse segment identification procedure to the transformed data in order to identify the CNV segments. This provides a computationally efficient approach for RD-based CNV identification. Simulation results show that this approach often results in a small number of false identifications of the CNVs and has similar or better performances in identifying the true CNVs when compared with other RD-based approaches. We demonstrate the methods using the trio data from the 1000 Genomes Project.

Simulating realistic genomic data with rare variants.

Increasing evidence suggests that rare and generally deleterious genetic variants might have a strong impact on disease risks of not only Mendelian disease, but also many common diseases. However, identifying such rare variants remains challenging, and novel statistical methods and bioinformatic software must be developed. Hence, we have to extensively evaluate various methods under reasonable genetic models. Although there are abundant genomic data, they are not most helpful for the evaluation of the methods because the disease mechanism is unknown. Thus, it is imperative that we simulate genomic data that mimic the real data containing rare variants and that enable us to impose a known disease penetrance model. Although resampling simulation methods have shown their advantages in computational efficiency and in preserving important properties such as linkage disequilibrium (LD) and allele frequency, they still have limitations as we demonstrated. We propose an algorithm that combines a regression-based imputation with resampling to simulate genetic data with both rare and common variants. Logistic regression model was employed to fit the relationship between a rare variant and its nearby common variants in the 1000 Genomes Project data and then applied to the real data to fill in one rare variant at a time using the fitted logistic model based on common variants. Individuals then were simulated using the real data with imputed rare variants. We compared our method with existing simulators and demonstrated that our method performed well in retaining the real sample properties, such as LD and minor allele frequency, qualitatively.

Expression of interferon-γ in decidual natural killer cells from women with hypertensive disorder complicating pregnancy.

AIM: Hypertensive disorder complicating pregnancy (HDCP) is one of the most frequent and serious pregnancy-related diseases, which is closely related to disorders of the maternal immune system, especially the local immune microenvironment of the maternal-fetal interface. Uterine decidual natural killer (dNK) cells are the major immune cells in the maternal-fetal interface and they play an important role in establishing and maintaining a normal pregnancy. The aim of this study was to investigate the phenotype and function of dNK cells from women with HDCP. MATERIAL AND METHODS: Decidual tissues were collected from women with normal pregnancy (normal control group, n = 15 cases) and HDCP (HDCP group, n = 20 cases), respectively. The mononuclear cells were extracted from tissues and flow cytometry (FCM) was utilized to sort out dNK cells. The phenotypes of dNK cells (CD56(bright)CD16⁻CD3⁻ vs CD56(dim)CD16⁺CD3⁻) were detected by FCM. After being co-cultured with Phorbol 12-myristate 13-acetate, ionomycin and monensin, the expression level of interferon (IFN)-γ in the dNK cells was detected by FCM. RESULTS: The phenotypes of dNK cells from the two groups were dominated by the CD56(bright)CD16⁻CD3⁻ subset, with no significant statistical difference (P < 0.05). The expression level of IFN-γ in the dNK cells from women with HDCP was on a lower trend than those from women with normal pregnancy, having significant statistical difference (P = 0.000 < 0.05). CONCLUSIONS: Our results indicated that although the phenotype of dNK cells from women with HDCP is of no difference, their functions are abnormal. Impaired cell function leads to a lower expression level of IFN-γ and this may account for one of the pathogeneses of HDCP.

Enhancing diagnosis of benign lesions and lung cancer through ensemble text and breath analysis: a retrospective cohort study.

Early diagnosis of lung cancer (LC) can significantly reduce its mortality rate. Considering the limitations of the high false positive rate and reliance on radiologists' experience in computed tomography (CT)-based diagnosis, a multi-modal early LC screening model that combines radiology with other non-invasive, rapid detection methods is warranted. A high-resolution, multi-modal, and low-differentiation LC screening strategy named ensemble text and breath analysis (ETBA) is proposed that ensembles radiology report text analysis and breath analysis. In total, 231 samples (140 LC patients and 91 benign lesions [BL] patients) were screened using proton transfer reaction-time of flight-mass spectrometry and CT screening. Participants were randomly assigned to a training set and a validation set (4:1) with stratification. The report section of the radiology reports was used to train a text analysis (TA) model with a natural language processing algorithm. Twenty-two volatile organic compounds (VOCs) in the exhaled breath and the prediction results of the TA model were used as predictors to develop the ETBA model using an extreme gradient boosting algorithm. A breath analysis model was developed based on the 22 VOCs. The BA and TA models were compared with the ETBA model. The ETBA model achieved a sensitivity of 94.3%, a specificity of 77.3%, and an accuracy of 87.7% with the validation set. The radiologist diagnosis performance with the validation set had a sensitivity of 74.3%, a specificity of 59.1%, and an accuracy of 68.1%. High sensitivity and specificity were obtained by the ETBA model compared with radiologist diagnosis. The ETBA model has the potential to provide sensitivity and specificity in CT screening of LC. This approach is rapid, non-invasive, multi-dimensional, and accurate for LC and BL diagnosis.

Bibliometric analysis of dendritic cell-based vaccines over the past 15 years.

Dendritic cells, which are crucial for inducing T-cell responses, are pivotal in current immunotherapy strategies aiming to replenish depleted T cells within the tumor microenvironment to combat tumors. Consequently, dendritic cell vaccine-based cancer therapies have garnered significant attention. Through bibliometric analysis, we examined research trends in this field. We searched the Web of Science core database and identified 16,476 articles on dendritic cell-based vaccines published from January 1, 2009, to December 30, 2023. The United States leads in this research domain, with Emory University being a prominent collaborator. The Journal of Immunology is the primary publication outlet, and Banchereau, J emerges as the most influential author. Recent hot keywords include nanoparticle, delivery, cancer vaccine, and clinical trial, indicating that cancer immunotherapy research, especially dendritic cell-based vaccines, is poised to become a future trend and hotspot.

A comprehensive assessment of the association between common drugs and psychiatric disorders using Mendelian randomization and real-world pharmacovigilance database.

BACKGROUND: Medications prescribed for chronic diseases can lead to short-term neuropsychiatric symptoms, but their long-term effects on brain structures and psychiatric conditions remain unclear. METHODS: We comprehensively analyzed the FDA Adverse Event Reporting System database and conducted drug target Mendelian Randomization (MR) studies on six categories of common drugs, 477 brain imaging-derived phenotypes (IDPs) and eight psychiatric disorders. Genetic instruments were extracted from expression quantitative trait loci (eQTLs) in blood, brain, and other target tissues, protein quantitative trait loci (pQTLs) in blood, and genome-wide association studies (GWAS) of hemoglobin and cholesterol. Summary statistics for brain IDPs, psychiatric disorders, and gut microbiome were obtained from the BIG40, Psychiatric Genomics Consortium, and MiBioGen. A two-step MR and mediation analysis were employed to screen possible mediators of drug-IDP effects from 119 gut microbiota genera and identify their mediation proportions. FINDINGS: Among 19 drug classes, six drugs were found to be associated with higher risks of psychiatric adverse events, while 11 drugs were associated with higher risks of gastrointestinal adverse events in the FAERS analysis. We identified ten drug-psychiatric disorder associations, 202 drug-IDP associations, 16 drug-microbiota associations, and four drug-microbiota-IDP causal links. For example, PPARG activation mediated HbA1c reduction caused a higher risk of bipolar disorder (BD) II. Genetically proxied GLP-1R agonists were significantly associated with an increase in the volume of the CA3-head of the right hippocampus and the area of the left precuneus cortex, both of which have been shown to correlate with cognition in previous studies. INTERPRETATION: Common drugs may affect brain structure and risk of psychiatric disorder. Oral medications in particular may exert some of these effects by influencing gut microbiota. This study calls for greater attention to be paid to the neuropsychiatric adverse effects of drugs and encourages drug repurposing. FUNDING: National Natural Science Foundation of China (grant No. 82330035, 82130043, 82172685, and 82001223), National Natural Science Foundation of Hunan Province (grant No. 2021SK1010), and the Science Foundation for Distinguished Young Scholars of Changsha (grant No. kq2209006).

Does the Level of Syndesmotic Screw Insertion Affect Clinical Outcome after Ankle Fractures with Syndesmotic Instability?

OBJECTIVE: Ankle fractures are often combined with syndesmotic instability, requiring reduction and stabilization. However, the optimal level for syndesmotic screw positioning remains unclear. This study aims to evaluate the effect of different syndesmotic screw insertion levels on postoperative clinical outcomes and determine whether an optimal level exists. METHODS: This retrospective study included data from 43 adult patients with acute closed ankle fractures combined with intraoperative evidence of unstable syndesmotic injuries who underwent open reduction internal fixation from January 1, 2017 to March 1, 2018 according to the inclusion and exclusion criteria. All 43 patients were divided into three groups based on the syndesmotic screw placement level: trans-syndesmotic group: screw level of 2-3 cm; inferior-syndesmotic group: screw level <2 cm; and supra-syndesmotic group: screw level >3 cm. Clinical outcomes were measured at the final follow-up, including the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Olerud-Molander Ankle Score (OMAS), short-form 36-item questionnaire (SF-36), visual analogue scale (VAS) score and restrictions in ankle range of motion (ROM). The relationships between screw placement level and clinical outcomes were analyzed with the Kruskal-Wallis H-test and Spearman correlation analysis. RESULTS: The median follow-up duration was 15 months (range, 10-22 months). No patients developed fracture nonunion or malunion or experienced hardware failure. The outcome scoring systems showed an overall score for the entire group of 94.91 points for the AOFAS ankle-hindfoot score, 83.14 for the OMAS, 96.65 for the SF-36, 1.77 for the VAS, 9.14° for the restrictions in dorsiflexion, and 1.30° for the restrictions in plantarflexion. There were no significant differences among three groups in clinical outcomes (P > 0.05). Neither the AOFAS score nor OMAS had significant correlations with screw insertion level (P = 0.825 and P = 0.585, respectively). No postoperative arthritis or widening of the tibiofibular space was observed at the final follow-up. CONCLUSION: Different syndesmotic screw placement levels appear not to affect the clinical outcomes of ankle fractures with syndesmotic instability. No optimal level was observed in this study. Our findings suggest other clinically acceptable options apart from syndesmotic screw placement 2-3 cm above the ankle.

Preparation, characterization, and evaluation of the antitumor effect of kaempferol nanosuspensions.

Kaempferol (KAE) is a naturally occurring flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability, and suboptimal bioavailability greatly restrict its clinical application in cancer therapy. To address the aforementioned limitations and augment the antitumor efficacy of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a stabilizing agent, screened the optimal preparation process, and conducted a comprehensive investigation of their fundamental properties as well as the antitumor effects in the study. The findings indicated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was prominently improved compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable and had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, along with increased intracellular ROS production and higher apoptosis rates compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps had a longer duration of action in mice, significantly improved bioavailability, and showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity in 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared notably improved the defect and the antitumor effects of KAE, making it a promising nanodrug delivery system for KAE with potential applications as a clinical antitumor drug.

The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice.

Resveratrol, curcumin, and quercetin are the secondary metabolites from medicinal food homology plants, that have been proven their potency in cancer treatment. However, the antitumor effect of a single component is weak. So, herein, we designed an antitumor compound named RCQ composed of resveratrol, curcumin, and quercetin. This study examined the effect on tumorigenesis and development of 4T1 breast cancer-bearing mice following administering RCQ by intragastric administration. RCQ increased the recruitment of T cells and reduced the accumulation of neutrophils and macrophages in the tumor microenvironment. Meanwhile, RCQ suppressed the development of tumor-infiltrating lymphocytes into immunosuppressive cell subpopulations, including CD4+ T cells to T helper Type 2 type (Th2), tumor-associated neutrophils (TANs) to the N2 TANs, and tumor-associated macrophages (TAMs) cells to M2 TAMs. RCQ reversed the predominance of immunosuppressive infiltrating cells in the tumor microenvironment and tipped the immune balance toward an immune activation state. In vitro the study showed that RCQ significantly increased reactive oxygen species (ROS), reduce mitochondrial membrane potentials in cancer cells, and modulate pro-apoptotic Bcl-2 family members. In conclusion, RCQ can promote the ROS apoptosis mechanism of tumor cells and alleviate immunosuppression of the tumor microenvironment to enhance the anti-tumor effect.

A combined screening study for evaluating the potential of exhaled acetone, isoprene, and nitric oxide as biomarkers of lung cancer.

Background: the early lung cancer (LC) screening strategy significantly reduces LC mortality. According to previous studies, lung cancer can be effectively diagnosed by analyzing the concentration of volatile organic compounds (VOCs) in human exhaled breath and establishing a diagnosis model based on the different VOCs. This method, called breath analysis, has the advantage of being rapid and non-invasive. To develop a non-invasive, portable breath detection instrument based on cavity ring-down spectroscopy (CRDS), we explored the feasibility of establishing a model with acetone, isoprene, and nitric oxide (NO) exhaled through human breath, which can be detected on the CRDS instrument. Methods: a total of 511 participants were recruited from the Cancer Institute and Hospital, Tianjin Medical University as the discovery set and randomly split (2 : 1) into training set and internal validation set with stratification. For external validation, 51 participants were recruited from the General Hospital, Tianjin Medical University. Acetone and isoprene from exhaled breath were detected by proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS), and NO was measured using CRDS. The model was constructed using the ensemble learning method that set eXtreme gradient boosting and logistic regression as the basis model and logistic regression as the senior model. The model was evaluated based on accuracy, sensitivity, and specificity. Results: the model achieved an accuracy of 78.8%, sensitivity of 81.0%, specificity of 70.0%, and area under the receiver operating curve (ROC, AUC) of 0.8341 (95% CI from 0.8055 to 0.8852) in the internal validation set. Furthermore, it attained an accuracy of 66.7%, sensitivity of 68.2%, specificity of 65.5%, and AUC of 0.6834 (95% CI from 0.5259 to 0.7956) in the external validation set. Conclusion: the model, established with acetone, isoprene, and NO as predictors, possesses the ability to identify LC patients from healthy control (HC) participants. The CRDS instrument, which simultaneously detects acetone, isoprene, and NO, is expected to be a non-invasive, rapid, portable, and accurate device for early screening of LC.

Synthesis of nano-Fe3O4/ZnO composites with enhanced antibacterial properties and plant growth promotion via one-pot reaction.

Bordeaux mixture is commonly used in agricultural production due to its certain antibacterial activity. However, it has been observed to promote plant growth at a slow pace. Therefore, it is crucial to explore an effective antibacterial agent that can enhance the antibacterial activity and promote plant growth in commercially available Bordeaux mixture, which can significantly contribute to the development of the agricultural economy. The investigation into inorganic agents with both bacteriostatic and plant-promoting properties has a broad application potential in agriculture. Fe3O4/ZnO (FZ) composites were synthesized from FeCl3, ZnCl2, and NaAc in a "one-pot approach" and analyzed using transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and a vibrating sample magnetometer (VSM). To investigate the antibacterial activity and mechanism of FZ nanocomposites, Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were used as model bacteria, and human mammary epithelial cells and model plant mung bean were used as targets to study the effects of FZ on human and plant growth. The results revealed that at 300 µg/mL for 80 min, the antibacterial efficacy of FZ composites was 99.8% against E. coli, which was 20% greater than that of Bordeaux liquid (FC), and 99.9% against S. aureus, which was 28.6% higher than that of FC. The inhibitory mechanism demonstrated that the substance could efficiently damage the bacterial cell wall of a concentration of 300 µg/mL. The IC50 of the material to human mammary epithelial cells was 49.518 µg/mL, and it also increased mung bean germination, root growth, and chlorophyll content, indicating that the application performance was 1.5 times better than that of FC. Its exceptional performance can be used to treat agricultural diseases.

Polydopamine-guarded metal-organic frameworks as co-delivery systems for starvation-assisted chemo-photothermal therapy.

Cutting off glucose provision by glucose oxidase (GOx) to famish tumors can be an assistance with chemotherapy to eliminate cancer cells. Co-encapsulation of GOx and chemotherapeutics (doxorubicin) within pH-sensitive metal-organic frameworks (MOFs) could disorder metabolic pathways of cancer cells and generate excessive intracellular reactive oxygen species (ROS), together. To prevent premature leach of GOx from the porous channels of MOFs, polydopamine (PDA) was deposited on the surface of MOFs, which endowed the delivery system with photothermal conversion ability. Our nanoscaled co-delivery system (denoted as DGZPNs) remains stable with low amount of drug leakage under simulated physiological conditions in vitro and internal environment, while they are triggered to release doxorubicin (DOX) and GOx in acid tumor microenvironment and at high temperature for reinforced chemotherapy. NIR laser irradiation also activates superior photothermal conversion efficiency of PDA (36.9 %) to initiate hyperthermia to ablate tumor tissue. After being phagocytized by 4 T1 cells (breast cancer cells), the DGZPNs delivery system showed a superior therapeutic efficacy with a tumor growth inhibition of 88.9 ± 6.6 % under NIR irradiation, which indicated that the starvation-assisted chemo-photothermal therapy prompts the significant advance of synergistic therapy in a parallelly controlled mode.

A diagnostic test of three-dimensional magnetic resonance elastography imaging for preoperative prediction of microvascular invasion in patients with T1 stage clear cell renal carcinoma.

Background: Detection of microvascular invasion (MVI) of kidney tumors is important for selecting the optimal therapeutic strategy. Currently, the prediction of MVI lacks an accurate imaging biomarker. This study evaluated the performance of three-dimensional (3D) magnetic resonance elastography (MRE) imaging in predicting microvascular invasion (MVI) of T1 stage clear cell renal carcinoma (ccRCC). Methods: In this prospective study, we conducted pre-surgical imaging with a clinical 3.0 T magnetic resonance imaging (MRI) system. Firstly, 83 consecutive patients were enrolled in this study. A 3D MRE stiffness map was generated and transferred to a post-processing workstation. Contrast-enhanced computed tomography (CT) was conducted to calculate the tumor enhancement ratio. The presence of MVI was evaluated by histopathological analysis and graded according to the risk stratification based upon the number and distribution. The mean stiffness and CT tumor enhancement ratio was calculated for tumors with or without MVI. The diagnostic performance [sensitivity, specificity, positive predictive value, negative predictive value, area under the curve (AUC)] and independent predicting factors for MVI were investigated. Results: Finally, A total of 80 patients (aged 46.7±13.2 years) were enrolled, including 22 cases of tumors with MVI. The mean MRE stiffness of kidney parenchyma and kidney tumors was 4.8±0.2 and 4.5±0.7 kPa, respectively. There was significant difference in the mean MRE stiffness between tumors with MVI (5.4±0.6 kPa) and tumors without MVI (4.1±0.3 kPa) (P<0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and the AUC for mean stiffness in the prediction of MVI were 100%, 75%, 63%, 96%, and 0.87 [95% confidence interval (CI): 0.72, 0.94], respectively. The corresponding values for the CT tumor enhancement ratio were 90%, 80%, 63%, 96%, and 0.88 (95% CI: 0.71, 0.93), respectively. The odds ratio (OR) value for MRE tumor stiffness and CT kidney tumor enhancement ratio in the prediction of MVI was 2.9 (95% CI: 1.8, 3.7) and 1.2 (95% CI: 1.0, 1.7), respectively (P>0.05). Conclusions: 3D MRE imaging has promising diagnostic performance for predicting MVI in T1 stage ccRCC, which may improve the reliability of surgical strategy selection with T1 stage ccRCC.

Cuproptosis-Related Risk Score Predicts Prognosis and Characterizes the Tumor Microenvironment in Hepatocellular Carcinoma.

Aims: Cuproptosis is a recently identified form of programmed cell death; however, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ferredoxin 1 (FDX1), the key regulator of cuproptosis. A cuproptosis-related risk score (CRRS) was developed via correlation analyses, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression. The metabolic features, mutation signatures, and immune profile of CRRS-classified HCC patients were investigated, and the role of CRRS in therapy guidance was analyzed. Results: FDX1 was significantly downregulated in HCC, and its high expression was associated with longer survival time. HCC patients in the high-CRRS group showed a significantly lower overall survival (OS) and enriched in cancer-related pathways. Mutation analyses revealed that the high-CRRS HCC patients had a high mutational frequency of some tumor suppressors such as tumor protein P53 (TP53) and Breast-cancer susceptibility gene 1 (BRCA1)-associated protein 1 (BAP1) and a low frequency of catenin beta 1 (CTNNB1). Besides, HCC patients with high CRRS showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve (AUC) values of CRRS in predicting the efficiency of sorafenib and the non-responsiveness to transcatheter arterial chemoembolization (TACE) in HCC patients reached 0.877 and 0.764, respectively. Significance: The cuproptosis-related signature is helpful in prognostic prediction and in guiding treatment for HCC patients.