A bibliometric analysis of the research landscape on vascular normalization in cancer.

Tumor vascular normalization profoundly affects the advancement of cancer therapy. Currently, with the rapid increase in research on tumor vascular normalization, few analytical and descriptive studies have investigated the trends in its development, key research power, present research hotspots, and future outlooks. In this study, articles and reviews published between January 1, 2003, and October 29, 2022 were retrieved from Web of Science database. Subsequently, published research trends, countries/regions, institutions, authors, journals, references, and keywords were analyzed based on traditional bibliometric laws (such as Price's exponential growth, Bradford's, Lotka's, and Zipf's). Our results showed that the last two decades have seen an increase in tumor vascular normalization research. USA emerged as the preeminent contributor to the field, boasting the highest H-index and accruing the greatest quantity of publications and citations. Among institutions, Massachusetts General Hospital and Harvard University made significant contributions, and Professor RK Jain was identified as a key leader in this field. Out of 583 academic journals, Cancer Research and Clinical Cancer Research published the most articles on vascular normalization. The research focal points in the field primarily include immunotherapy, tumor microenvironments, nanomedicine, and emerging frontier themes such as metabolism and mechanomedicine. Concurrently, the challenges of vascular normalization in cancer are discussed as well. In conclusion, the study presented a thorough analysis of the literature covering the past 20 years on vascular normalization in cancer, highlighting leading countries, institutions, authors, journals, and the emerging research focal points in this field. Future studies will advance the ongoing efforts in the field of tumor vascular normalization, aiming to enhance our ability to effectively manage and treat cancer.

Disproportion of Corpus Callosum in Fetuses With Malformations of Cortical Development.

OBJECTIVE: To evaluate corpus callosum (CC) size in fetuses with malformations of cortical development (MCD) and to explore the diagnostic value of three CC length (CCL) ratios in identifying cortical abnormalities. METHODS: This is a single-center retrospective study in singleton fetuses at 20-37 weeks of gestation between April 2017 and August 2022. The midsagittal plane of the fetal brain was obtained and evaluated for the following variables: length, height, area of the corpus callosum, and relevant markers, including the ratios of corpus callosum length to internal cranial occipitofrontal dimension (CCL/ICOFD), corpus callosum length to femur length (CCL/FL), and corpus callosum length to cerebellar vermian diameter (CCL/VD). Intra-class correlation coefficient (ICC) was used to evaluate measurement consistency. The accuracy of biometric measurements in prediction of MCD was assessed using the area under the receiver-operating-characteristics curves (AUC). RESULTS: Fetuses with MCD had a significantly decreased CCL, height (genu and splenium), and area as compared with those of normal fetuses (P < .05), but there was no significant difference in body height (P = .326). The CCL/ICOFD, CCL/FL, and CCL/VD ratios were significantly decreased in fetuses with MCD when compared with controls (P < .05). The CCL/ICOFD ratio offered the highest predictive accuracy for MCD, yielding an AUC of 0.856 (95% CI: 0.774-0.938, P < .001), followed by CCL/FL ratio (AUC, 0.780 (95% CI: 0.657-0.904), P < .001), CCL/VD ratio (AUC, 0.677 (95% CI: 0.559-0.795), P < .01). CONCLUSION: The corpus callosum biometric parameters in fetuses with MCD are reduced. The CCL/ICOFD ratio derived from sonographic measurements is considered a promising tool for the prenatal detection of cortical malformations. External validation of these findings and prospective studies are warranted.

DMC-siERCC2 hybrid nanoparticle enhances TRAIL sensitivity by inducing cell cycle arrest for glioblastoma treatment.

ERCC2 plays a pivotal role in DNA damage repair, however, its specific function in cancer remains elusive. In this study, we made a significant breakthrough by discovering a substantial upregulation of ERCC2 expression in glioblastoma (GBM) tumor tissue. Moreover, elevated levels of ERCC2 expression were closely associated with poor prognosis. Further investigation into the effects of ERCC2 on GBM revealed that suppressing its expression significantly inhibited malignant growth and migration of GBM cells, while overexpression of ERCC2 promoted tumor cell growth. Through mechanistic studies, we elucidated that inhibiting ERCC2 led to cell cycle arrest in the G0/G1 phase by blocking the CDK2/CDK4/CDK6/Cyclin D1/Cyclin D3 pathway. Notably, we also discovered a direct link between ERCC2 and CDK4, a critical protein in cell cycle regulation. Additionally, we explored the potential of TRAIL, a low-toxicity death ligand cytokine with anticancer properties. Despite the typical resistance of GBM cells to TRAIL, tumor cells undergoing cell cycle arrest exhibited significantly enhanced sensitivity to TRAIL. Therefore, we devised a combination strategy, employing TRAIL with the nanoparticle DMC-siERCC2, which effectively suppressed the GBM cell proliferation and induced apoptosis. In summary, our study suggests that targeting ERCC2 holds promise as a therapeutic approach to GBM treatment.

Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

Continuous production of ultratough semiconducting polymer fibers with high electronic performance.

Conjugated polymers have demonstrated promising optoelectronic properties, but their brittleness and poor mechanical characteristics have hindered their fabrication into durable fibers and textiles. Here, we report a universal approach to continuously producing highly strong, ultratough conjugated polymer fibers using a flow-enhanced crystallization (FLEX) method. These fibers exhibit one order of magnitude higher tensile strength (>200 megapascals) and toughness (>80 megajoules per cubic meter) than traditional semiconducting polymer fibers and films, outperforming many synthetic fibers, ready for scalable production. These fibers also exhibit unique strain-enhanced electronic properties and exceptional performance when used as stretchable conductors, thermoelectrics, transistors, and sensors. This work not only highlights the influence of fluid mechanical effects on the crystallization and mechanical properties of conjugated polymers but also opens up exciting possibilities for integrating these functional fibers into wearable electronics.

Effects of cadmium and zinc interactions on the physiological biochemistry and enrichment characteristics of Iris pseudacorus.

Compound pollution with cadmium (Cd) and zinc (Zn) is common in nature. The effects of compounded Cd and Zn on the growth and development of Iris pseudacorus in the environment and the plant's potential to remediate heavy metals in the environment remain unclear. In this study, the effects of single and combined Cd and Zn stress on I. pseudacorus growth and the enrichment of heavy metals in I. pseudacorus seedlings were investigated. The results showed that under Cd (160 µM) and Zn (800 µM) stress, plant growth was significantly inhibited and photosynthetic performance was affected. Cd+Zn200 (160 µM + 200 µM) reduced the levels of malondialdehyde, hydrogen peroxide, and non-protein thiols by 31.29%, 53.20%, and 13.29%, respectively, in the aboveground tissues compared with levels in the single Cd treatment. However, Cd+Zn800 (160 µM + 800 µM) had no effect. Cd and Zn800 inhibited the absorption of mineral elements, while Zn200 had little effect on plants. Compared with that for Cd treatment alone, Cd + Zn200 and Cd+Zn800 reduced the Cd content in aboveground tissues by 54.15% and 49.92%, respectively, but had no significant effect on Cd in the root system. Zn significantly reduced the Cd content in subcellular components and limited the content and proportion of Cd extracted using water and ethanol. These results suggest that a low supply of Zn reduces Cd accumulation in aboveground tissues by promoting antioxidant substances and heavy metal chelating agents, thus protecting the photosynthetic systems. The addition of Zn also reduced the mobility and bioavailability of Cd to alleviate its toxicity in I. pseudacorus.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice.

Ultrasound is an acoustic wave which can noninvasively penetrate the skull to deep brain regions, enabling neuromodulation. However, conventional ultrasound's spatial resolution is diffraction-limited and low-precision. Here, we report acoustic nanobubble-mediated ultrasound stimulation capable of localizing ultrasound's effects to only the desired brain region in male mice. By varying the delivery site of nanobubbles, ultrasound could activate specific regions of the mouse motor cortex, evoking EMG signaling and limb movement, and could also, separately, activate one of two nearby deep brain regions to elicit distinct behaviors (freezing or rotation). Sonicated neurons displayed reversible, low-latency calcium responses and increased c-Fos expression in the sub-millimeter-scale region with nanobubbles present. Ultrasound stimulation of the relevant region also modified depression-like behavior in a mouse model. We also provide evidence of a role for mechanosensitive ion channels. Altogether, our treatment scheme allows spatially-targetable, repeatable and temporally-precise activation of deep brain circuits for neuromodulation without needing genetic modification.

Comparative stigmatic transcriptomics reveals self and cross pollination responses to heteromorphic incompatibility in Plumbago auriculata Lam.

"Heteromorphic self-incompatibility" (HetSI) in plants is a mechanism of defense to avoid self-pollination and promote outcrossing. However, the molecular mechanism underlying HetSI remains largely unknown. In this study, RNA-seq was conducted to explore the molecular mechanisms underlying self-compatible (SC, "T × P" and "P × T") and self-incompatible (SI, "T × T" and "P × P") pollination in the two types of flowers of Plumbago auriculata Lam. which is a representative HetSI plant. By comparing "T × P" vs. "T × T", 3773 (1407 upregulated and 2366 downregulated) differentially expressed genes (DEGs) were identified, 1261 DEGs between "P × T" and "P × P" (502 upregulated and 759 downregulated). The processes in which these DEGs were significantly enriched were "MAPK (Mitogen-Activated Protein Kinases-plant) signaling pathway", "plant-pathogen interaction","plant hormone signal transduction", and "pentose and glucuronate interconversion" pathways. Surprisingly, we discovered that under various pollination conditions, multiple notable genes that may be involved in HetSI exhibited distinct regulation. We can infer that the HetSI strategy might be unique in P. auriculata. It was similar to "sporophytic self-incompatibility" (SSI) but the HetSI mechanisms in pin and thrum flowers are diverse. In this study, new hypotheses and inferences were proposed, which can provide a reference for crop production and breeding.

Quasi-Static Modeling Framework for Soft Bellow-Based Biomimetic Actuators.

Soft robots that incorporate elastomeric matrices and flexible materials have gained attention for their unique capabilities, surpassing those of rigid robots, with increased degrees of freedom and movement. Research has highlighted the adaptability, agility, and sensitivity of soft robotic actuators in various applications, including industrial grippers, locomotive robots, wearable assistive devices, and more. It has been demonstrated that bellow-shaped actuators exhibit greater efficiency compared to uniformly shaped fiber-reinforced actuators as they require less input pressure to achieve a comparable range of motion (ROM). Nevertheless, the mathematical quantification of the performance of bellow-based soft fluidic actuators is not well established due to their inherent non-uniform and complex structure, particularly when compared to fiber-reinforced actuators. Furthermore, the design of bellow dimensions is mostly based on intuition without standardized guidance and criteria. This article presents a comprehensive description of the quasi-static analytical modeling process used to analyze bellow-based soft actuators with linear extension. The results of the models are validated through finite element method (FEM) simulations and experimental testing, considering elongation in free space under fluidic pressurization. This study facilitates the determination of optimal geometrical parameters for bellow-based actuators, allowing for effective biomimetic robot design optimization and performance prediction.

Ultrastable N-Type Semiconducting Fiber Organic Electrochemical Transistors for Highly Sensitive Biosensors.

Organic electrochemical transistors (OECTs) have attracted increasing attention due to their merits of high transconductance, low operating voltage, and good biocompatibility, ideal for biosensors. However, further advances in their practical applications face challenges of low n-type performance and poor stability. Here, it is demonstrated that wet-spinning the commercially available n-type conjugated polymer poly(benzimidazobenzophenanthroline) (BBL) into highly aligned and crystalline fibers enhances both OECT performance and stability. Although BBL is only soluble in high-boiling-point strong acids, it can be wet-spun into high-quality fibers with adjustable diameters. The BBL fiber OECTs exhibit a record-high area-normalized transconductance (gm,A ) of 2.40 µS µm-2 and over 10 times higher figure-of-merit (µC*) than its thin-film counterparts. More importantly, these fiber OECTs exhibit remarkable stability with no noticeable performance attenuation after 1500 cycles over 4 h operation, outperforming all previously reported n-type OECTs. The superior performance and stability can be attributed to shorter π-π stacking distance and ordered molecular arrangement in the fibers, endowing the BBL fiber OECT-based biosensors with outstanding sensitivity while keeping a miniaturized form factor. This work demonstrates that, beyond new material development, developing new fabrication technology is also crucial for addressing the performance and stability issues in n-type OECTs.

Successful surgical management of a superior cerebellar artery aneurysm in a patient with Marfan syndrome: illustrative case.

BACKGROUND: Marfan syndrome, a connective tissue disorder, poses unique challenges in neurosurgery, given the fragility of vascular structures. Superior cerebellar artery (SCA) aneurysms in patients with the syndrome are rare and present distinct surgical difficulties, necessitating innovative approaches. OBSERVATIONS: A 29-year-old male with Marfan syndrome presented with a subarachnoid hemorrhage from a ruptured SCA aneurysm. Given the lack of a defined aneurysm neck and the small diameter of the SCA, standard clipping and endovascular therapies were unsuitable. A microsurgical approach using microsutures was successfully employed, effectively managing the aneurysm while preserving the parent artery. LESSONS: This case underscores the efficacy of the microsuture technique in complex neurosurgical scenarios, particularly in patients with connective tissue disorders such as Marfan syndrome. The adaptability of surgical strategies, as demonstrated in this case, is crucial for achieving successful outcomes in patients with unique anatomical challenges.

A flavonoid metabolon: cytochrome b5 enhances B-ring trihydroxylated flavan-3-ols synthesis in tea plants.

Flavan-3-ols are prominent phenolic compounds found abundantly in the young leaves of tea plants. The enzymes involved in flavan-3-ol biosynthesis in tea plants have been extensively investigated. However, the localization and associations of these numerous functional enzymes within cells have been largely neglected. In this study, we aimed to investigate the synthesis of flavan-3-ols in tea plants, particularly focusing on epigallocatechin gallate. Our analysis involving the DESI-MSI method to reveal a distinct distribution pattern of B-ring trihydroxylated flavonoids, primarily concentrated in the outer layer of buds. Subcellular localization showed that CsC4H, CsF3'H, and CsF3'5'H localizes endoplasmic reticulum. Protein-protein interaction studies demonstrated direct associations between CsC4H, CsF3'H, and cytoplasmic enzymes (CHS, CHI, F3H, DFR, FLS, and ANR), highlighting their interactions within the biosynthetic pathway. Notably, CsF3'5'H, the enzyme for B-ring trihydroxylation, did not directly interact with other enzymes. We identified cytochrome b5 isoform C serving as an essential redox partner, ensuring the proper functioning of CsF3'5'H. Our findings suggest the existence of distinct modules governing the synthesis of different B-ring hydroxylation compounds. This study provides valuable insights into the mechanisms underlying flavonoid diversity and efficient synthesis and enhances our understanding of the substantial accumulation of B-ring trihydroxylated flavan-3-ols in tea plants.

Classification and hemodynamic characteristics of delayed intracerebral hemorrhage following stent-assisted coil embolism in unruptured intracranial aneurysms.

Background and objective: Stent-assisted coil (SAC) embolization is a commonly used endovascular treatment for unruptured intracranial aneurysms (UIAs) but can be associated with symptomatic delayed intracerebral hemorrhage (DICH). Our study aimed to investigate the hemodynamic risk factors contributing to DICH following SAC embolization and to establish a classification for DICH predicated on hemodynamic profiles. Methods: This retrospective study included patients with UIAs located in the internal carotid artery (ICA) treated with SAC embolization at our institution from January 2021 to January 2022. We focused on eight patients who developed postoperative DICH and matched them with sixteen control patients without DICH. Using computational fluid dynamics, we evaluated the hemodynamic changes in distal arteries [terminal ICA, the anterior cerebral artery (ACA), and middle cerebral artery (MCA)] pre-and post-embolization. We distinguished DICH-related arteries from unrelated ones (ACA or MCA) and compared their hemodynamic alterations. An imbalance index, quantifying the differential in flow velocity changes between ACA and MCA post-embolization, was employed to gauge the flow distribution in distal arteries was used to assess distal arterial flow distribution. Results: We identified two types of DICH based on postoperative flow alterations. In type 1, there was a significant lower in the mean velocity increase rate of the DICH-related artery compared to the unrelated artery (-47.25 ± 3.88% vs. 42.85 ± 3.03%; p < 0.001), whereas, in type 2, there was a notable higher (110.58 ± 9.42% vs. 17.60 ± 4.69%; p < 0.001). Both DICH types demonstrated a higher imbalance index than the control group, suggesting an association between altered distal arterial blood flow distribution and DICH occurrence. Conclusion: DICH in SAC-treated UIAs can manifest as either a lower (type 1) or higher (type 2) in the rate of velocity in DICH-related arteries. An imbalance in distal arterial blood flow distribution appears to be a significant factor in DICH development.

Radiomics nomogram based on MRI water imaging identifying symptomatic nerves of patients with primary trigeminal neuralgia: A preliminary study.

The study proposes a combined nomogram based on radiomics features from magnetic resonance neurohydrography and clinical features to identify symptomatic nerves in patients with primary trigeminal neuralgia. We retrospectively analyzed 140 patients with clinically confirmed trigeminal neuralgia. Out of these, 24 patients constituted the external validation set, while the remaining 116 patients contributed a total of 231 nerves, comprising 118 symptomatic nerves, and 113 normal nerves. Radiomics features were extracted from the MRI water imaging (t2-mix3d-tra-spair). Radiomics feature selection was performed using L1 regularization-based regression, while clinical feature selection utilized univariate analysis and multivariate logistic regression. Subsequently, radiomics, clinical, and combined models were developed by using multivariate logistic regression, and a nomogram of the combined model was drawn. The performance of nomogram in discriminating symptomatic nerves was assessed through the area under the curve (AUC) of receiver operating characteristics, accuracy, and calibration curves. Clinical applications of the nomogram were further evaluated using decision curve analysis. Five clinical factors and 13 radiomics signatures were ultimately selected to establish predictive models. The AUCs in the training and validation cohorts were 0.77 (0.70-0.84) and 0.82 (0.72-0.92) with the radiomics model, 0.69 (0.61-0.77) and 0.66 (0.53-0.79) with the clinical model, 0.80 (0.74-0.87), and 0.85 (0.76-0.94) with the combined model, respectively. In the external validation set, the AUCs for the clinical, radiomics, and combined models were 0.70 (0.60-0.79), 0.78 (0.65-0.91), and 0.81 (0.70-0.93), respectively. The calibration curve demonstrated that the nomogram exhibited good predictive ability. Moreover, The decision curve analysis curve indicated shows that the combined model holds high clinical application value. The integrated model, combines radiomics features from magnetic resonance neurohydrography with clinical factors, proves to be effective in identify symptomatic nerves in trigeminal neuralgia. The diagnostic efficacy of the combined model was notably superior to that of the model constructed solely from conventional clinical features.

The thalamic covariance network is associated with cognitive deficits in patients with cerebral small vascular disease.

OBJECTIVE: Abnormalities in the gray matter structure of cerebral small vessel disease (CSVD) have been observed throughout the brain. However, whether cortico-cortical connections exist between regions of gray matter atrophy in patients with CSVD has not been fully elucidated. This question was tested by comparing the gray matter covariance networks in CSVD patients with and without cognitive impairment (CI). METHODS: We performed multivariate modeling of the gray matter volume measurements of 61 patients with CI (CSVD-CI), 85 patients without CI (CSVD-NC), and 108 healthy controls using source-based morphological analysis (SBM) to obtain gray matter structural covariance networks at the population level. Then, correlations between structural covariance networks and cognitive functions were analyzed in CSVD patients. Finally, a support vector machine (SVM) classifier was used with the gray matter covariance network as a classification feature to identify CI among the CSVD population. RESULTS: The results of the analysis of all the subjects showed that compared with healthy controls, the expression of the thalamic covariance network, cerebellum covariance network, and calcarine cortex covariance network was reduced in patients with CSVD. Moreover, CSVD-CI patients showed a significant reduction in the expression of the thalamic covariance network, encompassing the thalamus and the parahippocampal gyrus, relative to CSVD-NC patients, which persisted after excluding CSVD patients with thalamic lacunes. In patients with CSVD, cognitive functions were positively correlated with measures of the thalamic covariance network. More than 80% of CSVD patients with CI were correctly identified by the SVM classifier. INTERPRETATION: Our findings provide new evidence to explain the distribution state of gray matter reduction in CSVD patients, and the thalamic covariance network is the core region for early gray matter reduction during the development of CSVD disease, which is related to cognitive deficits. Reduced expression of thalamic covariance networks may provide a neuroimaging biomarker for the early identification of cognitive impairment in CSVD patients.

DNAJC12 causes breast cancer chemotherapy resistance by repressing doxorubicin-induced ferroptosis and apoptosis via activation of AKT.

BACKGROUND: Chemotherapy is a primary treatment for breast cancer (BC), yet many patients develop resistance over time. This study aims to identify critical factors contributing to chemoresistance and their underlying molecular mechanisms, with a focus on reversing this resistance. METHODS: We utilized samples from the Gene Expression Omnibus (GEO) and West China Hospital to identify and validate genes associated with chemoresistance. Functional studies were conducted using MDA-MB-231 and MCF-7 cell lines, involving gain-of-function and loss-of-function approaches. RNA sequencing (RNA-seq) identified potential mechanisms. We examined interactions between DNAJC12, HSP70, and AKT using co-immunoprecipitation (Co-IP) assays and established cell line-derived xenograft (CDX) models for in vivo validations. RESULTS: Boruta analysis of four GEO datasets identified DNAJC12 as highly significant. Patients with high DNAJC12 expression showed an 8 % pathological complete response (pCR) rate, compared to 38 % in the low expression group. DNAJC12 inhibited doxorubicin (DOX)-induced cell death through both ferroptosis and apoptosis. Combining apoptosis and ferroptosis inhibitors completely reversed DOX resistance caused by DNAJC12 overexpression. RNA-seq suggested that DNAJC12 overexpression activated the PI3K-AKT pathway. Inhibition of AKT reversed the DOX resistance induced by DNAJC12, including reduced apoptosis and ferroptosis, restoration of cleaved caspase 3, and decreased GPX4 and SLC7A11 levels. Additionally, DNAJC12 was found to increase AKT phosphorylation in an HSP70-dependent manner, and inhibiting HSP70 also reversed the DOX resistance. In vivo studies confirmed that AKT inhibition reversed DNAJC12-induced DOX resistance in the CDX model. CONCLUSION: DNAJC12 expression is closely linked to chemoresistance in BC. The DNAJC12-HSP70-AKT signaling axis is crucial in mediating resistance to chemotherapy by suppressing DOX-induced ferroptosis and apoptosis. Our findings suggest that targeting AKT and HSP70 activities may offer new therapeutic strategies to overcome chemoresistance in BC.

Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Diabetic conditions promote drug coating degradation but prevent endothelial coverage after stenting.

The endothelialization of drug-eluting stents is delayed after implantation in patients with diabetes. Although numerous factors were implicated in hyperglycemia-induced endothelial dysfunction, the effects of stent drug coating degradation on endothelial dysfunction remains unclear. We hypothesized that diabetic conditions promote drugcoating degradation and enhance antiproliferative agent release, but that the rapid release of these antiproliferative agents inhibits endothelial cell proliferation leading to poor reendothelialization post-stenting. To verify this hypothesis, a dynamic hyperglycemic circulation system was introduced to measure the profile of drugcoating degradation in vitro. Flow cytometry and RNA sequencing were performed to evaluate endothelial cell proliferation. Moreover, a Type 1 diabetic rabbit model was generated and a rescue experiment conducted to evaluate the effects of rapid drugcoating elution on endothelial coverage in vivo. The main findings were as follows: 1) diabetic conditions promoted drugcoating degradation and increased antiproliferative agent release; 2) this increase in antiproliferative agent release inhibited endothelial cell proliferation and delayed endothelial coverage; and 3) strict glycemic control attenuated drugcoating degradation and promoted endothelial coverage post-stenting. This is the first study to illustrate rapid drugcoating degradation and its potential effects on endothelial recovery under diabetic conditions, highlighting the importance of strict glycemic management in patients with diabetes after drug-eluting stent implantation. STATEMENT OF SIGNIFICANCE: Diabetic conditions promote drug coating degradation and increase the release of antiproliferative agents. Rapid drug coating degradation under diabetic conditions inhibits endothelial cell proliferation and delays endothelialization. Strict glycemic control attenuates drug coating degradation and promotes endothelialization.